Pub Date : 2023-03-16DOI: 10.2174/2210303113666230316124601
T. Ikoma, Hajime Watanabe, Yasuhiro Nakagawa, S. Hattori, T. Minowa, N. Hanagata
Anti-sclerostin antibodies are among the most efficient drugs for the treatment of osteoporosis, and have been also expected for the treatment of local bone disorders. We have previously developed porous microparticles of hydroxyapatite and chondroitin sulfate loading anti-sclerostin antibodies formulated with zinc cations. However, the biological behavior and concentration dependence of anti-sclerostin antibodies in vitro released from the microparticles remain unclear. Bolus administration and the subsequent release of anti-sclerostin antibodies from the microparticles formulated with or without zinc cations were investigated; bone-resorptive inhibitory effects on mouse MC3T3-E1 osteoblast function were revealed by cell culture using a cell culture insert plate. Differentiation induction culture of osteoblasts was performed after maintaining the concentrations of anti-sclerostin antibodies and sclerostin at previously reported concentrations of 5.0 and 1.0 µg/mL for the first 3 days. Subsequently, the medium was replaced with fresh medium that did not contain anti-sclerostin antibodies but microparticles loading anti-sclerostin antibodies (20 or 80 µg/mg) with or without zinc cations in the cell culture insert. After 11 days of incubation, the bioactivity of the osteoblasts was evaluated using the polymerase chain reaction method. The formulation using zinc cations showed an increase of anti-sclerostin antibodies released from the microparticles, which increased the expression of receptor activator of the nuclear factor kappa-B ligand in the osteoblasts on day 14. This result indicates the inhibition of sclerostin-mediated bone resorption. However, the increase of loading amounts of anti-sclerostin antibodies extremely enhanced the subsequent release of anti-sclerostin antibodies, which decreased the inhibition of bone resorption contrary to expectations. The moderately sustained release of anti-sclerostin antibodies from the microparticles can promote the inhibition of bone resorption in osteoblasts, supporting the potential of this formulation for the treatment of localized bone disorders.
{"title":"Effects of Anti-Sclerostin Antibody Release from Porous Microparticles on Bone Resorption Inhibition of Osteoblasts","authors":"T. Ikoma, Hajime Watanabe, Yasuhiro Nakagawa, S. Hattori, T. Minowa, N. Hanagata","doi":"10.2174/2210303113666230316124601","DOIUrl":"https://doi.org/10.2174/2210303113666230316124601","url":null,"abstract":"\u0000\u0000Anti-sclerostin antibodies are among the most efficient drugs for the treatment of osteoporosis, and have been also expected for the treatment of local bone disorders. We have previously developed porous microparticles of hydroxyapatite and chondroitin sulfate loading anti-sclerostin antibodies formulated with zinc cations. However, the biological behavior and concentration dependence of anti-sclerostin antibodies in vitro released from the microparticles remain unclear.\u0000\u0000\u0000\u0000Bolus administration and the subsequent release of anti-sclerostin antibodies from the microparticles formulated with or without zinc cations were investigated; bone-resorptive inhibitory effects on mouse MC3T3-E1 osteoblast function were revealed by cell culture using a cell culture insert plate.\u0000\u0000\u0000\u0000Differentiation induction culture of osteoblasts was performed after maintaining the concentrations of anti-sclerostin antibodies and sclerostin at previously reported concentrations of 5.0 and 1.0 µg/mL for the first 3 days. Subsequently, the medium was replaced with fresh medium that did not contain anti-sclerostin antibodies but microparticles loading anti-sclerostin antibodies (20 or 80 µg/mg) with or without zinc cations in the cell culture insert. After 11 days of incubation, the bioactivity of the osteoblasts was evaluated using the polymerase chain reaction method.\u0000\u0000\u0000\u0000The formulation using zinc cations showed an increase of anti-sclerostin antibodies released from the microparticles, which increased the expression of receptor activator of the nuclear factor kappa-B ligand in the osteoblasts on day 14. This result indicates the inhibition of sclerostin-mediated bone resorption. However, the increase of loading amounts of anti-sclerostin antibodies extremely enhanced the subsequent release of anti-sclerostin antibodies, which decreased the inhibition of bone resorption contrary to expectations.\u0000\u0000\u0000\u0000The moderately sustained release of anti-sclerostin antibodies from the microparticles can promote the inhibition of bone resorption in osteoblasts, supporting the potential of this formulation for the treatment of localized bone disorders.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47300884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dexamethasone (DEX) is a glucocorticosteroid used in the treatment of steroid-responsive inflammatory conditions of the eye. The currently marketed formulations pose several issues, like poor drug residence time, resulting in frequent administration of the formulation, making them less effective. The present study aims to provide comprehensive data encompassing the designing, optimization, development, and characterization of DEX nanoemulsion (DEX NE) for treating inflammatory conditions of the anterior segment of the eye by employing the Quality by Design (QbD) approach. A Plackett-Burman Design (PBD) was employed to screen seven independent variables, such as oil concentration, surfactant concentration, polymer concentration, homogenization speed and time, microfluidization pressure and cycles, and their influence on critical quality attributes (CQAs), such as globule size, zeta potential, and viscosity, was evaluated. Furthermore, the Box-Behnken design (BBD) was employed for optimization, and design space was generated to obtain the optimized DEX NE. The experimental results after DEX NE characterization reveal a globule size of 181 ±90 nm with a zeta potential of -21.03 ±1.68 mV and a viscosity of 19.99 cp. Furthermore, the drug release study of simulated tear fluid demonstrated prolonged and steady release for up to 48 hr. Cytotoxicity assay of DEX NE exhibited good cell viability. All these findings pave the way for a better understanding of developing a robust, safe, and non-toxic formulation for ocular drug delivery. -
{"title":"Development and In-vitro Evaluation of Dexamethasone Enriched Nanoemulsion for Ophthalmic Indication","authors":"Derajram Benival, Ajinkya Jadhav, Sagar Salave, Dhwani Rana","doi":"10.2174/2210303113666230309151048","DOIUrl":"https://doi.org/10.2174/2210303113666230309151048","url":null,"abstract":"\u0000\u0000Dexamethasone (DEX) is a glucocorticosteroid used in the treatment of steroid-responsive inflammatory conditions of the eye. The currently marketed formulations pose several issues, like poor drug residence time, resulting in frequent administration of the formulation, making them less effective.\u0000\u0000\u0000\u0000The present study aims to provide comprehensive data encompassing the designing, optimization, development, and characterization of DEX nanoemulsion (DEX NE) for treating inflammatory conditions of the anterior segment of the eye by employing the Quality by Design (QbD) approach.\u0000\u0000\u0000\u0000A Plackett-Burman Design (PBD) was employed to screen seven independent variables, such as oil concentration, surfactant concentration, polymer concentration, homogenization speed and time, microfluidization pressure and cycles, and their influence on critical quality attributes (CQAs), such as globule size, zeta potential, and viscosity, was evaluated. Furthermore, the Box-Behnken design (BBD) was employed for optimization, and design space was generated to obtain the optimized DEX NE.\u0000\u0000\u0000\u0000The experimental results after DEX NE characterization reveal a globule size of 181 ±90 nm with a zeta potential of -21.03 ±1.68 mV and a viscosity of 19.99 cp. Furthermore, the drug release study of simulated tear fluid demonstrated prolonged and steady release for up to 48 hr. Cytotoxicity assay of DEX NE exhibited good cell viability.\u0000\u0000\u0000\u0000All these findings pave the way for a better understanding of developing a robust, safe, and non-toxic formulation for ocular drug delivery.\u0000\u0000\u0000\u0000-\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46295801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-07DOI: 10.2174/2210303113666230307115408
S. Nayak, S. Jammula, C. Patra, G. Jena, K. C. Panigrahi, N. K. Kumar
Cinacalcet hydrochloride (CINH) is a BCS class IV drug. It is mainly used for the treatment of chronic renal disease and parathyroid cancer. It exhibits poor oral bioavailability of less than 25%. The main objective is to improve the bioavailability of CINH by formulating the nanostructure lipid carrier (NLC). : In this research, glyceryl monostearate (GMS), labrasol, and tween 20 were the main excipients selected for the formulation of NLC. Hot high-speed homogenization and ultra-sonication method was used for the NLC formulation of CINH. The characterization of the NLCs was done as per standard procedures. Optimization of the formulated NLC was carried out by applying Box-Behnken Design (BBD) with the help of the Design Expert software. The pharmacokinetic study was conducted to determine the improvement in the bioavailability of the CINH. The cytotoxicity study was performed by using the MTT assay method to know the cell viability. The optimized NLC formulation exhibited high drug content with a particle size of less than 200nm. A pharmacokinetic study showed 4 fold increase in oral bioavailability for the optimized NLC in comparison to the aqueous suspension of CINH. Minimum viability was determined as 94%, which indicates the safety of the incubated formulations. NLC formulation has the potential to improve oral bioavailability with high drug loading and cell viability for CINH.
{"title":"Nanostructured Lipid Carrier of Cinacalcet HCl: Formulation, BBD enabled Optimization, Pharmacokinetic and In-Vitro Cytotoxicity Study","authors":"S. Nayak, S. Jammula, C. Patra, G. Jena, K. C. Panigrahi, N. K. Kumar","doi":"10.2174/2210303113666230307115408","DOIUrl":"https://doi.org/10.2174/2210303113666230307115408","url":null,"abstract":"\u0000\u0000Cinacalcet hydrochloride (CINH) is a BCS class IV drug. It is mainly used for the treatment of chronic renal disease and parathyroid cancer. It exhibits poor oral bioavailability of less than 25%.\u0000\u0000\u0000\u0000The main objective is to improve the bioavailability of CINH by formulating the nanostructure lipid carrier (NLC).\u0000\u0000\u0000\u0000: In this research, glyceryl monostearate (GMS), labrasol, and tween 20 were the main excipients selected for the formulation of NLC. Hot high-speed homogenization and ultra-sonication method was used for the NLC formulation of CINH. The characterization of the NLCs was done as per standard procedures. Optimization of the formulated NLC was carried out by applying Box-Behnken Design (BBD) with the help of the Design Expert software. The pharmacokinetic study was conducted to determine the improvement in the bioavailability of the CINH. The cytotoxicity study was performed by using the MTT assay method to know the cell viability.\u0000\u0000\u0000\u0000The optimized NLC formulation exhibited high drug content with a particle size of less than 200nm. A pharmacokinetic study showed 4 fold increase in oral bioavailability for the optimized NLC in comparison to the aqueous suspension of CINH. Minimum viability was determined as 94%, which indicates the safety of the incubated formulations.\u0000\u0000\u0000\u0000NLC formulation has the potential to improve oral bioavailability with high drug loading and cell viability for CINH.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49584455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-21DOI: 10.2174/2210303113666230221100526
Aliasgar F. Shahiwala, R. Sammour, S. H. Almurisi, M. Taher
This study aims to assess the suitability of in vitro drug release methods, dialysis and paddle methods for predicting in vivo behaviour of Aceclofenac (ACE) proniosomes. In vitro dissolution methods can mimic in vivo dissolution behaviour of BCS Class II drug and compounds belonging to this are eligible to establish a significant in vitro in vivo correlation (IVIVC). Therefore, the appropriate selection of dissolution test conditions is important to have a method able to discriminate among drug products with potential problems of bioavailability ACE proniosomes are prepared using different carriers: glucose, maltodextrin and mannitol by the slurry method. The release studies of ACE proniosomes formulations were performed using the paddle, and dialysis methods while in vivo studies were performed in albino rats. Graphical presentation, model-dependent and model-independent approaches were applied to compare two dissolution methods. The objective of this work was to establish a point-to-point (level A) relationship between the in vitro dissolution and the in vivo absorption rate of ACE from the proniosomal system. More than 70% of the drug was released from ACE proniosomes over 60 min by paddle method while not more than 5% was released in the same period by dialysis method. The paddle method provides a reproducible and faster release, whereas poor drug release occurred with the dialysis method. For the paddle method, lower values of similarity factor (f2) and greater differences in the dissolution efficiency (DE) amongst different formulations and in comparison, to that of the pure drug indicates that it is a more discriminative method compared to dialysis. The paddle method also illustrated high regression coefficients (r2) of 0.81, 0.998 and 0.975 for FN1, FN2, and FN3, respectively for level A IVIVC, while poor or no relation (r2 < 0.1) was detected in the case of dialysis method. Based on the results, the paddle method is concluded to be the more suitable method compared to the dialysis method for in vitro drug release studies of a novel dosage form such as proniosomes. Based on the results, the paddle method is concluded to be the more suitable method compared to the dialysis method for in vitro drug release studies of a novel dosage form such as proniosomes.
{"title":"Proniosomes For Oral Delivery Of Aceclofenac: Impact Of Paddle Versus Dialysis Methods On In Vitro-In Vivo Correlation (Ivivc) Predictions","authors":"Aliasgar F. Shahiwala, R. Sammour, S. H. Almurisi, M. Taher","doi":"10.2174/2210303113666230221100526","DOIUrl":"https://doi.org/10.2174/2210303113666230221100526","url":null,"abstract":"\u0000\u0000This study aims to assess the suitability of in vitro drug release methods, dialysis and paddle methods for predicting in vivo behaviour of Aceclofenac (ACE) proniosomes.\u0000\u0000\u0000\u0000In vitro dissolution methods can mimic in vivo dissolution behaviour of BCS Class II drug and compounds belonging to this are eligible to establish a significant in vitro in vivo correlation (IVIVC). Therefore, the appropriate selection of dissolution test conditions is important to have a method able to discriminate among drug products with potential problems of bioavailability\u0000\u0000\u0000\u0000ACE proniosomes are prepared using different carriers: glucose, maltodextrin and mannitol by the slurry method. The release studies of ACE proniosomes formulations were performed using the paddle, and dialysis methods while in vivo studies were performed in albino rats. Graphical presentation, model-dependent and model-independent approaches were applied to compare two dissolution methods.\u0000\u0000\u0000\u0000The objective of this work was to establish a point-to-point (level A) relationship between the in vitro dissolution and the in vivo absorption rate of ACE from the proniosomal system.\u0000\u0000\u0000\u0000More than 70% of the drug was released from ACE proniosomes over 60 min by paddle method while not more than 5% was released in the same period by dialysis method. The paddle method provides a reproducible and faster release, whereas poor drug release occurred with the dialysis method. For the paddle method, lower values of similarity factor (f2) and greater differences in the dissolution efficiency (DE) amongst different formulations and in comparison, to that of the pure drug indicates that it is a more discriminative method compared to dialysis. The paddle method also illustrated high regression coefficients (r2) of 0.81, 0.998 and 0.975 for FN1, FN2, and FN3, respectively for level A IVIVC, while poor or no relation (r2 < 0.1) was detected in the case of dialysis method.\u0000\u0000\u0000\u0000Based on the results, the paddle method is concluded to be the more suitable method compared to the dialysis method for in vitro drug release studies of a novel dosage form such as proniosomes.\u0000\u0000\u0000\u0000Based on the results, the paddle method is concluded to be the more suitable method compared to the dialysis method for in vitro drug release studies of a novel dosage form such as proniosomes.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48404433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-02DOI: 10.2174/2210303113666230202153647
M. Nagarsenker, Neelam Shah, Saurabh Katawale, Sanket M. Shah, V. Dhawan
The present study evaluates the feasibility of the incorporation of palmitoylated arabinogalactan in solid lipid nanoparticles and its potential as a hepatospecific targeting ligand. Human hepatocellular carcinoma (HCC) is a neoplasm presenting low survival and higher incidence, due to difficulties in the treatment modalities to effectively place cancer therapeutics at the site. Targeting asialoglycoprotein receptors on the surface of hepatocytes employing lipid nanoparticles, and liposomes presents opportunities for improvement in therapy. The objective of the present investigation was to fabricate and evaluate the potential of palmitoylated arabinogalactan (PAG) incorporated SLNs to target asialoglycoprotein receptors. Daunorubicin-loaded targeted SLNs prepared by ultrasound dispersion method were evaluated for in vitro release and in vitro cytotoxicity. Lipids, surfactants, and biocompatible solvents were screened for SLN formation and optimization was done using 22 factorial designs. The particle size for formulations was below 200 nm with a unimodal distribution. Differential scanning calorimetry analysis revealed the interaction of lipids with other components characterized by a shift in lipid melting endotherm. Daunorubicin-loaded PAG SLNs released a significantly higher amount of daunorubicin at pH 5.5 as compared to pH 7.4, providing an advantage for targeted tumor therapy. In vitro cytotoxicity studies showed that daunorubicin depicted a dose-dependent reduction in viability in all cell lines treated with formulation as well as free drug. SLNs showed enhancement in intracellular uptake of daunorubicin thereby establishing their potential in improved treatment of HCC and warrant further in vivo investigations. -
{"title":"Exploring palmitoylated arabinogalactan in solid lipid nanoparticles: formulation design and in vitro assessment for hepatospecific targeting","authors":"M. Nagarsenker, Neelam Shah, Saurabh Katawale, Sanket M. Shah, V. Dhawan","doi":"10.2174/2210303113666230202153647","DOIUrl":"https://doi.org/10.2174/2210303113666230202153647","url":null,"abstract":"\u0000\u0000The present study evaluates the feasibility of the incorporation of palmitoylated arabinogalactan in solid lipid nanoparticles and its potential as a hepatospecific targeting ligand.\u0000\u0000\u0000\u0000Human hepatocellular carcinoma (HCC) is a neoplasm presenting low survival and higher incidence, due to difficulties in the treatment modalities to effectively place cancer therapeutics at the site. Targeting asialoglycoprotein receptors on the surface of hepatocytes employing lipid nanoparticles, and liposomes presents opportunities for improvement in therapy.\u0000\u0000\u0000\u0000The objective of the present investigation was to fabricate and evaluate the potential of palmitoylated arabinogalactan (PAG) incorporated SLNs to target asialoglycoprotein receptors.\u0000\u0000\u0000\u0000Daunorubicin-loaded targeted SLNs prepared by ultrasound dispersion method were evaluated for in vitro release and in vitro cytotoxicity. Lipids, surfactants, and biocompatible solvents were screened for SLN formation and optimization was done using 22 factorial designs.\u0000\u0000\u0000\u0000The particle size for formulations was below 200 nm with a unimodal distribution. Differential scanning calorimetry analysis revealed the interaction of lipids with other components characterized by a shift in lipid melting endotherm. Daunorubicin-loaded PAG SLNs released a significantly higher amount of daunorubicin at pH 5.5 as compared to pH 7.4, providing an advantage for targeted tumor therapy. In vitro cytotoxicity studies showed that daunorubicin depicted a dose-dependent reduction in viability in all cell lines treated with formulation as well as free drug.\u0000\u0000\u0000\u0000SLNs showed enhancement in intracellular uptake of daunorubicin thereby establishing their potential in improved treatment of HCC and warrant further in vivo investigations.\u0000\u0000\u0000\u0000-\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47588573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-26DOI: 10.2174/2210303113666230126103055
S. Swain, Sasikanth Kothamasu, M. E. Bhanoji Rao, B. R. Jena
The prime intent of this study was to formulate, optimize and evaluate the floating microballoons of rosuvastatin calcium to extend the stomach or gastrointestinal residence time, dissolution rate, and bioavailability of the drug. Objective: Rosuvastatin calcium-loaded floating microballoons were prepared by solvent evaporation technique and systematic optimization of such formulations by response surface methodology using Box-Behnken Design, with the selected independent variables like concentration of HPMC K4M (X1), K15M (X2), and K100M (X3) and dependent variables as mean particle size in µm (R1), % entrapment efficiency (R2), and % drug released at 12h (R3). For each of the studied response variables, the trial formulations were subsequently evaluated for in vitro floating lag time, drug content, total floating time, and drug content, and the data analysis through optimization was carried out by placing the experimental data with an appropriate mathematical model. In vivo pharmacokinetics study parameters for the optimized batch showed a 4 to 5 folds elevation of peak plasma concentration (Cmax), the area under the curve (AUC) data, and reduction of time to reach peak concentration (Tmax) value compared to marketed product (p<0.05). As per ICH guidelines, the stability study results show that floating microballoons remain stable for 6 months. Hence, the floating microballoons of rosuvastatin calcium are a valuable technique to improve the solubility, dissolution, and bioavailability of a poorly water-soluble drug, rosuvastatin calcium.
{"title":"QbD Driven Formulation Development, Optimization of Rosuvastatin Calcium Loaded Floating Microballoons: In Vitro and In Vivo Characterization","authors":"S. Swain, Sasikanth Kothamasu, M. E. Bhanoji Rao, B. R. Jena","doi":"10.2174/2210303113666230126103055","DOIUrl":"https://doi.org/10.2174/2210303113666230126103055","url":null,"abstract":"\u0000\u0000The prime intent of this study was to formulate, optimize and evaluate the floating microballoons of rosuvastatin calcium to extend the stomach or gastrointestinal residence time, dissolution rate, and bioavailability of the drug.\u0000\u0000\u0000\u0000Objective: Rosuvastatin calcium-loaded floating microballoons were prepared by solvent evaporation technique and systematic optimization of such formulations by response surface methodology using Box-Behnken Design, with the selected independent variables like concentration of HPMC K4M (X1), K15M (X2), and K100M (X3) and dependent variables as mean particle size in µm (R1), % entrapment efficiency (R2), and % drug released at 12h (R3).\u0000\u0000\u0000\u0000For each of the studied response variables, the trial formulations were subsequently evaluated for in vitro floating lag time, drug content, total floating time, and drug content, and the data analysis through optimization was carried out by placing the experimental data with an appropriate mathematical model.\u0000\u0000\u0000\u0000In vivo pharmacokinetics study parameters for the optimized batch showed a 4 to 5 folds elevation of peak plasma concentration (Cmax), the area under the curve (AUC) data, and reduction of time to reach peak concentration (Tmax) value compared to marketed product (p<0.05). As per ICH guidelines, the stability study results show that floating microballoons remain stable for 6 months.\u0000\u0000\u0000\u0000Hence, the floating microballoons of rosuvastatin calcium are a valuable technique to improve the solubility, dissolution, and bioavailability of a poorly water-soluble drug, rosuvastatin calcium.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44966291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-20DOI: 10.2174/2210303113666230120124831
A. Dharamsi, T. Pandya
Present research work aims to develop Chitosan nanoparticles of leuprolide acetate for intranasal delivery in the treatment of Alzheimer’s disease. Alzheimer’s disease (AD) is one of the leading causes and the most prevalent form of age-related dementia worldwide. There is an urgent surge to find an effective treatment for AD due to the social implications it poses on society. To formulate Leuprolide acetate chitosan nanoparticles for intranasal delivery Chitosan nanoparticles encapsulating leuprolide acetate were prepared using the ionic gelation method and optimized using a central composite design. The optimized nanoparticles were evaluated by DSC study, TEM analysis, in vitro and ex vivo drug release study, histopathology study, and accelerated stability study, In vivo kinetic and dynamic study. The optimized formulation exhibited particle size of 254.3 ± 10.7 nm, Thus, the chitosan nanoparticulate formulation of leuprolide acetate was found to have great potential for Alzheimer’s disease management. NA
{"title":"Intranasal delivery of leuprolide acetate chitosan nanoparticles for treatment of Alzheimer’s disease","authors":"A. Dharamsi, T. Pandya","doi":"10.2174/2210303113666230120124831","DOIUrl":"https://doi.org/10.2174/2210303113666230120124831","url":null,"abstract":"\u0000\u0000Present research work aims to develop Chitosan nanoparticles of leuprolide acetate for intranasal delivery in the treatment of Alzheimer’s disease.\u0000\u0000\u0000\u0000Alzheimer’s disease (AD) is one of the leading causes and the most prevalent form of age-related dementia worldwide. There is an urgent surge to find an effective treatment for AD due to the social implications it poses on society.\u0000\u0000\u0000\u0000To formulate Leuprolide acetate chitosan nanoparticles for intranasal delivery\u0000\u0000\u0000\u0000Chitosan nanoparticles encapsulating leuprolide acetate were prepared using the ionic gelation method and optimized using a central composite design. The optimized nanoparticles were evaluated by DSC study, TEM analysis, in vitro and ex vivo drug release study, histopathology study, and accelerated stability study, In vivo kinetic and dynamic study.\u0000\u0000\u0000\u0000The optimized formulation exhibited particle size of 254.3 ± 10.7 nm, \u0000\u0000\u0000\u0000Thus, the chitosan nanoparticulate formulation of leuprolide acetate was found to have great potential for Alzheimer’s disease management.\u0000\u0000\u0000\u0000NA\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68161012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-27DOI: 10.2174/2210303113666221227145210
B. Sharma, Iti Chauhan, A. Singh
In humans, Carotenoids are important in scavenging singlet oxygen and peroxyl radicals. Lutein has been demonstrated in multiple studies to help protect the skin from photodamage, as well as provide a variety of other health advantages. In the recent decade, the topical use of Lutein as a new ultraviolet (UV) protectant, anti-stress, and blue light filter capable of protecting skin from photodamage has piqued cosmetic and pharmacological attention. Because Lutein is insoluble, it was integrated into nanocarriers for topical administration. The objective of this study was to formulate an NLC-based sunscreen gel of Lutein. Nanostructured lipid carriers (NLC) were prepared by melt emulsion ultrafiltration technique and were evaluated for particle size, zeta potential, polydispersity index (PDI), drug loading(DL), encapsulation efficacy(EE), and in vitro drug release. The optimised formula was incorporated into a gel base and an in-vitro sun protection factor (SPF) was determined. Ex- vivo permeation study was performed on rat skin using a Franz diffusion cell. Cocoa butter and rose oil were chosen as solid and liquid lipids for NLC formulation. The particle size, PDI, zeta potential, entrapment efficiency, and in vitro drug release of optimised formulation (NLC5) were found to be 81.64 nm, 0.463, -14.1mV, 79.90 %, and 89.86% respectively. The SPF value of the Lutein-NLC-loaded gel was found to be 27.524. The NLC gel Jss (g/cm2/h) was measured in the range of 0.07955 g/cm2/h. The investigation suggested lipid nanoparticles as a suitable carrier for Lutein to be delivered as sunscreen gel.
{"title":"Development of NLC- based sunscreen gel of Lutein and its in-vitro and ex-vivo characterisation","authors":"B. Sharma, Iti Chauhan, A. Singh","doi":"10.2174/2210303113666221227145210","DOIUrl":"https://doi.org/10.2174/2210303113666221227145210","url":null,"abstract":"\u0000\u0000In humans, Carotenoids are important in scavenging singlet oxygen and peroxyl radicals. Lutein has been demonstrated in multiple studies to help protect the skin from photodamage, as well as provide a variety of other health advantages. In the recent decade, the topical use of Lutein as a new ultraviolet (UV) protectant, anti-stress, and blue light filter capable of protecting skin from photodamage has piqued cosmetic and pharmacological attention. Because Lutein is insoluble, it was integrated into nanocarriers for topical administration.\u0000\u0000\u0000\u0000The objective of this study was to formulate an NLC-based sunscreen gel of Lutein.\u0000\u0000\u0000\u0000Nanostructured lipid carriers (NLC) were prepared by melt emulsion ultrafiltration technique and were evaluated for particle size, zeta potential, polydispersity index (PDI), drug loading(DL), encapsulation efficacy(EE), and in vitro drug release. The optimised formula was incorporated into a gel base and an in-vitro sun protection factor (SPF) was determined. Ex- vivo permeation study was performed on rat skin using a Franz diffusion cell. Cocoa butter and rose oil were chosen as solid and liquid lipids for NLC formulation.\u0000\u0000\u0000\u0000The particle size, PDI, zeta potential, entrapment efficiency, and in vitro drug release of optimised formulation (NLC5) were found to be 81.64 nm, 0.463, -14.1mV, 79.90 %, and 89.86% respectively. The SPF value of the Lutein-NLC-loaded gel was found to be 27.524. The NLC gel Jss (g/cm2/h) was measured in the range of 0.07955 g/cm2/h.\u0000\u0000\u0000\u0000The investigation suggested lipid nanoparticles as a suitable carrier for Lutein to be delivered as sunscreen gel.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46705576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-26DOI: 10.2174/2210303113666221226092547
Abdelrahman Y. Sherif, G. I. Harisa, F. Alanazi
The present study aimed to prepare and optimize solid lipid nanoparticles (SLN) consisting of fatty acids (FAs; stearic acid), that are actively uptaken by cancer cells. Enhance cytotoxic activity of chemotherapeutic agent required to increase drug safety profile. The present study aimed to prepare and optimize solid lipid nanoparticles (SLN) consisting of fatty acids (FAs; stearic acid), that are actively uptaken by cancer cells. Stability of the prepared SLN formulations was characterized for 90 days. The most stable formulations were loaded with GEF (GEF-SLN) and subjected to pharmaceutical characterization. In-vitro dissolution of GEF-SLN was studied using the dialysis method. Biosafety in the terms of hemocompatibility of the prepared SLN was investigated using fresh blood samples. Additionally, cytotoxicity of GEF-SLN was investigated using the A549 cell line as a surrogate model for lung cancer. The present results revealed that the prepared SLN formulations were homogeneously distributed in the nanosize range from (114 to 411 nm) with a negative zeta potential value from (-17 to -27 mV). The drug loading increased the particle size of SLN compared to the plain-SLN. Furthermore, PXRD results showed that the degree of stearic acid crystallization was disrupted by the presence of GEF. GEF entrapment efficiency into SLN 88% with a sustained-release profile of about 75% GEF was liberated in 24 h. Hemocompatibility results revealed that all SLN formulations showed insignificant hemolysis (1- 4%) at all concentrations. Moreover, cytotoxicity studies showed that SLN improves GEF anticancer effect compared to free GEF. These data concluded that, SLN promising approach to enhancing the selective deposition of GEF into cancer cells and reducing the lymphatic metastasis of lung cancer. None
{"title":"SLN Mediate Active Delivery of Gefitinib into A549 Cell Line: Optimization, Biosafety, and Cytotoxicity Studies","authors":"Abdelrahman Y. Sherif, G. I. Harisa, F. Alanazi","doi":"10.2174/2210303113666221226092547","DOIUrl":"https://doi.org/10.2174/2210303113666221226092547","url":null,"abstract":"\u0000\u0000The present study aimed to prepare and optimize solid lipid nanoparticles (SLN) consisting of fatty acids (FAs; stearic acid), that are actively uptaken by cancer cells.\u0000\u0000\u0000\u0000Enhance cytotoxic activity of chemotherapeutic agent required to increase drug safety profile.\u0000\u0000\u0000\u0000The present study aimed to prepare and optimize solid lipid nanoparticles (SLN) consisting of fatty acids (FAs; stearic acid), that are actively uptaken by cancer cells.\u0000\u0000\u0000\u0000Stability of the prepared SLN formulations was characterized for 90 days. The most stable formulations were loaded with GEF (GEF-SLN) and subjected to pharmaceutical characterization. In-vitro dissolution of GEF-SLN was studied using the dialysis method. Biosafety in the terms of hemocompatibility of the prepared SLN was investigated using fresh blood samples. Additionally, cytotoxicity of GEF-SLN was investigated using the A549 cell line as a surrogate model for lung cancer.\u0000\u0000\u0000\u0000The present results revealed that the prepared SLN formulations were homogeneously distributed in the nanosize range from (114 to 411 nm) with a negative zeta potential value from (-17 to -27 mV). The drug loading increased the particle size of SLN compared to the plain-SLN. Furthermore, PXRD results showed that the degree of stearic acid crystallization was disrupted by the presence of GEF. GEF entrapment efficiency into SLN 88% with a sustained-release profile of about 75% GEF was liberated in 24 h. Hemocompatibility results revealed that all SLN formulations showed insignificant hemolysis (1- 4%) at all concentrations. Moreover, cytotoxicity studies showed that SLN improves GEF anticancer effect compared to free GEF.\u0000\u0000\u0000\u0000These data concluded that, SLN promising approach to enhancing the selective deposition of GEF into cancer cells and reducing the lymphatic metastasis of lung cancer.\u0000\u0000\u0000\u0000None\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45741070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-07DOI: 10.2174/2210303113666221207142644
Shreya Shirodkar, R. Pissurlenkar
Owing to presystemic metabolism following oral drug delivery, most antihypertensive medications have a low bioavailability. Cilnidipine is a calcium channel blocker used to treat mild to moderate hypertension. Cilnidipine's bioavailability is reduced by 13% due to substantial presystemic metabolism. The study aimed to fabricate non-irritant and stable microsponge-based hydrogel to enhance the bioavailability of cilnidipine, a weakly water-soluble medication. In addition, the goal was to enhance the permeation rate and retention time at the site of application. Formulation was developed by using a two-level factorial design with Design Expert software version 13 (14-day free trial). Microsponges were formulated by the emulsion solvent diffusion method, followed by evaluating responses, such as particle size, percentage entrapment efficiency, in vitro drug release, and surface morphology. In addition, X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FT-IR) were performed. Viscosity, swelling behaviour, spreadability, in vitro diffusion, skin irritancy using Wistar albino rats, and in vitro permeation using goat skin were assessed, and stability studies were performed after incorporating the finest formulation into the gel base. Fabricated microsponges were found to be within the required micro dimensions having the necessary porous morphology as demonstrated by scanning electron microscopy studies. Drug entrapment efficiency was found to be in the range of 75-88%. The extended medicament release duration of up to 8 hours was observed. The diffusion data showed controlled release, as demonstrated by Higuchi’s plot. In vitro permeation studies displayed enhanced medicament retention and permeation rate at the site of application. The fabricated microsponge drug delivery system was found to be stable, non-irritant, and having enhanced permeation rate and retention time.
{"title":"Formulation and Characterisation of Cilnidipine Microsponge Loaded Hydrogels for Antihypertensive Activity","authors":"Shreya Shirodkar, R. Pissurlenkar","doi":"10.2174/2210303113666221207142644","DOIUrl":"https://doi.org/10.2174/2210303113666221207142644","url":null,"abstract":"\u0000\u0000Owing to presystemic metabolism following oral drug delivery, most antihypertensive medications have a low bioavailability. Cilnidipine is a calcium channel blocker used to treat mild to moderate hypertension. Cilnidipine's bioavailability is reduced by 13% due to substantial presystemic metabolism.\u0000\u0000\u0000\u0000The study aimed to fabricate non-irritant and stable microsponge-based hydrogel to enhance the bioavailability of cilnidipine, a weakly water-soluble medication. In addition, the goal was to enhance the permeation rate and retention time at the site of application.\u0000\u0000\u0000\u0000Formulation was developed by using a two-level factorial design with Design Expert software version 13 (14-day free trial). Microsponges were formulated by the emulsion solvent diffusion method, followed by evaluating responses, such as particle size, percentage entrapment efficiency, in vitro drug release, and surface morphology. In addition, X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FT-IR) were performed. Viscosity, swelling behaviour, spreadability, in vitro diffusion, skin irritancy using Wistar albino rats, and in vitro permeation using goat skin were assessed, and stability studies were performed after incorporating the finest formulation into the gel base.\u0000\u0000\u0000\u0000Fabricated microsponges were found to be within the required micro dimensions having the necessary porous morphology as demonstrated by scanning electron microscopy studies. Drug entrapment efficiency was found to be in the range of 75-88%. The extended medicament release duration of up to 8 hours was observed. The diffusion data showed controlled release, as demonstrated by Higuchi’s plot. In vitro permeation studies displayed enhanced medicament retention and permeation rate at the site of application.\u0000\u0000\u0000\u0000The fabricated microsponge drug delivery system was found to be stable, non-irritant, and having enhanced permeation rate and retention time.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48229203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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