Background: A lyophilizate for dry powder inhalation (LDPI) system is unique in that its formulation, a lyophilized cake, is aerosolized just upon inhalation by convection flow of air. An LDPI system may be advantageous, especially for biopharmaceutics, such as proteins and peptides, because formulations can be manufactured without high temperature and shear stress. It was already reported that formulations of peptides used in an LDPI system showed high aerosolization performance. However, it was not confirmed whether the LDPI system could deliver drugs efficiently enough for practical use. Objective: In this study, we compared the drug delivery efficiency of an LDPI system with intravenous and subcutaneous injections. Methods: We administered LDPI formulations containing ghrelin as model formulations to monkeys and measured pharmacokinetic profiles. Results: As a result of pharmacokinetics testing in the monkeys, the relative bioavailability of an inhaled drug compared to subcutaneous injection was 24-92%. The LDPI system showed high relative bioavailability based on the fact that the relative bioavailability of inhaled insulin was 10- 30%. Conclusion: It is expected that the LDPI system can deliver drugs efficiently enough for practical use even in the systemic application of bio-pharmaceutics.
{"title":"Efficiency of a Lyophilizate for Dry Powder Inhalation System for Drug Delivery of Ghrelin in Monkeys","authors":"Tomomi Akita, Kahori Miyamoto, Chikamasa Yamashita","doi":"10.2174/0122103031265565230921103638","DOIUrl":"https://doi.org/10.2174/0122103031265565230921103638","url":null,"abstract":"Background: A lyophilizate for dry powder inhalation (LDPI) system is unique in that its formulation, a lyophilized cake, is aerosolized just upon inhalation by convection flow of air. An LDPI system may be advantageous, especially for biopharmaceutics, such as proteins and peptides, because formulations can be manufactured without high temperature and shear stress. It was already reported that formulations of peptides used in an LDPI system showed high aerosolization performance. However, it was not confirmed whether the LDPI system could deliver drugs efficiently enough for practical use. Objective: In this study, we compared the drug delivery efficiency of an LDPI system with intravenous and subcutaneous injections. Methods: We administered LDPI formulations containing ghrelin as model formulations to monkeys and measured pharmacokinetic profiles. Results: As a result of pharmacokinetics testing in the monkeys, the relative bioavailability of an inhaled drug compared to subcutaneous injection was 24-92%. The LDPI system showed high relative bioavailability based on the fact that the relative bioavailability of inhaled insulin was 10- 30%. Conclusion: It is expected that the LDPI system can deliver drugs efficiently enough for practical use even in the systemic application of bio-pharmaceutics.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135901377","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 : 2023-09-15DOI: 10.2174/2210303113666230915103016
Surjeet Kaur Sethi, Honey Goel, Viney Chawla
Abstract: Fungal infections are one of the significant causes of death worldwide. Antifungal agents are associated with several side effects and toxicities while treating these infections. To overcome these physicochemical and pharmacokinetic side effects of antifungal agents, supramolecular drug delivery systems can be employed. The emulsion-based supramolecular assemblies, i.e., microemulsion and nanoemulsion, can be functionalized to achieve targeted delivery of antifungal drugs at the desired body sites. Emulsion based supramolecular assemblies have the ability to minimize the side effects related to antifungal agents and enhance their efficacy and safety profile. The present review focuses on the severe fungal infections and antifungal agents available for their management with their drawbacks. This review also introduces various emulsion-based supramolecular drug delivery approaches that may improve the usability of antifungal agents or reduce their side effects to treat fungal infections.
{"title":"Nanoemulsion based Supramolecular Drug Delivery Systems for Therapeutic Management of fungal Infections","authors":"Surjeet Kaur Sethi, Honey Goel, Viney Chawla","doi":"10.2174/2210303113666230915103016","DOIUrl":"https://doi.org/10.2174/2210303113666230915103016","url":null,"abstract":"Abstract: Fungal infections are one of the significant causes of death worldwide. Antifungal agents are associated with several side effects and toxicities while treating these infections. To overcome these physicochemical and pharmacokinetic side effects of antifungal agents, supramolecular drug delivery systems can be employed. The emulsion-based supramolecular assemblies, i.e., microemulsion and nanoemulsion, can be functionalized to achieve targeted delivery of antifungal drugs at the desired body sites. Emulsion based supramolecular assemblies have the ability to minimize the side effects related to antifungal agents and enhance their efficacy and safety profile. The present review focuses on the severe fungal infections and antifungal agents available for their management with their drawbacks. This review also introduces various emulsion-based supramolecular drug delivery approaches that may improve the usability of antifungal agents or reduce their side effects to treat fungal infections.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135438623","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 : 2023-08-30DOI: 10.2174/2210303113666230830125337
A. Pandey, U. Sara
The second most common cause of mortality by cancer is thought to be colorectal cancer, which is one of the most prevalent tumours in the world. Many health advantages have been linked to curcumin, which is the key component of turmeric. The goal of the current study was to create a colon-targeted microbead method coated with Eudragit S100 to improve curcumin targeting in the colon by speeding up the rate of its dissolution. The ionotropic gelation process was used to create the formulations. The surface phenomena, bead shape, entrapment effectiveness, drug loading, and in vitro drug release were all assessed for formulations. Moreover, calcium alginate beads with an improved core were enteric coated with Eudragit S100. The polymer concentration and curing duration significantly affected particle size and entrapment effectiveness, respectively. The particle size of the improved formulation was 705 µm, drug entrapment efficiency was 83.56%, drug loading was 28.64%, and in vitro release was 81.66% after 6 hours in phosphate buffer at pH 6.8. After 10 hours, enteric coating with Eudragit S100 of optimized calcium alginate microbeads revealed a 64.09±0.16% drug release. The calculated values of the regression coefficients for the Higuchi, first-order, and zero-order models were 0.9494, 0.8913, and 0.9579, respectively. The 50% inhibitory concentration value was 2.676 based on the percentage of cell viability. To effectively treat colorectal cancer, the enteric-coated calcium alginate microbeads can deliver curcumin selectively to the colon when taken orally.
{"title":"Colon Targeted Delivery and In Vitro Evaluation of Curcumin for Colon Cancer","authors":"A. Pandey, U. Sara","doi":"10.2174/2210303113666230830125337","DOIUrl":"https://doi.org/10.2174/2210303113666230830125337","url":null,"abstract":"\u0000\u0000The second most common cause of mortality by cancer is thought to be colorectal cancer, which is one of the most prevalent tumours in the world. Many health advantages have been linked to curcumin, which is the key component of turmeric. The goal of the current study was to create a colon-targeted microbead method coated with Eudragit S100 to improve curcumin targeting in the colon by speeding up the rate of its dissolution.\u0000\u0000\u0000\u0000The ionotropic gelation process was used to create the formulations. The surface phenomena, bead shape, entrapment effectiveness, drug loading, and in vitro drug release were all assessed for formulations. Moreover, calcium alginate beads with an improved core were enteric coated with Eudragit S100. The polymer concentration and curing duration significantly affected particle size and entrapment effectiveness, respectively.\u0000\u0000\u0000\u0000The particle size of the improved formulation was 705 µm, drug entrapment efficiency was 83.56%, drug loading was 28.64%, and in vitro release was 81.66% after 6 hours in phosphate buffer at pH 6.8. After 10 hours, enteric coating with Eudragit S100 of optimized calcium alginate microbeads revealed a 64.09±0.16% drug release. The calculated values of the regression coefficients for the Higuchi, first-order, and zero-order models were 0.9494, 0.8913, and 0.9579, respectively. The 50% inhibitory concentration value was 2.676 based on the percentage of cell viability.\u0000\u0000\u0000\u0000To effectively treat colorectal cancer, the enteric-coated calcium alginate microbeads can deliver curcumin selectively to the colon when taken orally.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48842750","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 : 2023-08-18DOI: 10.2174/2210303113666230818113653
Nisha V Kalayil, P. Paul, Showkhiya Y. Khan, Shona S. D'Souza
The goal of precision medicine is to create treatments for a single person or group of people based on information about their physical condition in the present and the past as well as their exposure to the environment. Precision medicine is now having an impact on how people are treated for their health at different periods of their lives through a variety of applications. Applications of precision medicine can help prevent death, alert patients regarding genetic risks, lower medical expenses, and enhance the quality of life. To determine the risk that a child may inherit an illness, genetic testing is performed before conception. The most severe type of brain cancer is glioblastoma (GBM), commonly referred to as grade IV astrocytoma. Although they can penetrate the brain, GBMs normally do not spread to other organs. One effective kind of treatment for glioblastoma is precision medicine, which is currently being developed. Numerous improvements in diagnosis and therapy have resulted in the healing of many patients without having an impact on their way of life. In terms of diagnosis and treatment, this article compares and contrasts precision technology and traditional therapy. Stem cell treatment, immunotherapy, and combination therapy are all extensively described.
{"title":"Advancing Glioblastoma Therapy: Promising Research in Precision Medicine","authors":"Nisha V Kalayil, P. Paul, Showkhiya Y. Khan, Shona S. D'Souza","doi":"10.2174/2210303113666230818113653","DOIUrl":"https://doi.org/10.2174/2210303113666230818113653","url":null,"abstract":"\u0000\u0000The goal of precision medicine is to create treatments for a single person or group of people based on information about their physical condition in the present and the past as well as their exposure to the environment. Precision medicine is now having an impact on how people are treated for their health at different periods of their lives through a variety of applications. Applications of precision medicine can help prevent death, alert patients regarding genetic risks, lower medical expenses, and enhance the quality of life. To determine the risk that a child may inherit an illness, genetic testing is performed before conception. The most severe type of brain cancer is glioblastoma (GBM), commonly referred to as grade IV astrocytoma. Although they can penetrate the brain, GBMs normally do not spread to other organs. One effective kind of treatment for glioblastoma is precision medicine, which is currently being developed. Numerous improvements in diagnosis and therapy have resulted in the healing of many patients without having an impact on their way of life. In terms of diagnosis and treatment, this article compares and contrasts precision technology and traditional therapy. Stem cell treatment, immunotherapy, and combination therapy are all extensively described.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44754184","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 : 2023-06-22DOI: 10.2174/2210303113666230622123933
Farhat Naz, Arun Kumar, Pankaj Prabhakar, S. Lale
The development of safe and biocompatible nanoparticles has always been a major concern in nanomedicine applications. Various studies on the size-dependent toxicity of nanoparticles have been reported but are still controversial. The potential of small-sized nanoparticles can be utilized for imaging and diagnostics. However, insufficient toxicity data on these nanoparticles prevents researchers from utilizing their potential in diagnostics. More studies are needed on the toxicity of small-sized nanoparticles to present unanimous report for safe systemic use. The present study aimed to investigate the toxicity concerns of very small-sized AuNPs (2±0.5 nm, 5±1 nm, and 10±2 nm) and provide a platform for their safe in vivo use. The cellular interactions of these three small-sized AuNPs with regard to cytotoxicity were investigated on hepatocellular carcinoma (HepG2) and epithelial kidney (HEK-293) cell lines. The cytotoxicity investigation of both cell lines was done through MTT assays, PI & DAPI, and cytology. Cellular stress was investigated by Catalase, TBARS, GSH, SOD & ROS parameters. The AuNPs incubated cells were also assessed for immunogenicity by ELISA, protein interaction by BSA, and cellular internalization by TEM (Edax). All three-sized AuNPs were not toxic on cell viability, apoptosis, necrosis, or cytology assessment. No oxidative stress was noted in both cell types in the presence of 2 and 5-nm-sized AuNPs, whereas 10 nm-sized AuNPs showed little oxidative stress. AuNPs of size 2 and 5 nm were immunologically inert, but 10 nm-sized AuNPs elicited interleukin (IL-4 and IL-10) and interferon IFN gamma response. AuNPs of sized 2 nm showed 4 times the adsorption of albumin protein as compared to AuNPs of sized 5 nm. The TEM micrographs and peak of gold in the Edax graph confirmed the presence of AuNPs in cells. Our results are suggestive of utilizing the potential of these three-sized AuNPs safely in preclinical drug delivery applications.
{"title":"“In-vitro Safety Assessment of Ultrasmall Gold Nanoparticles for Preclinical Drug Delivery Applications”","authors":"Farhat Naz, Arun Kumar, Pankaj Prabhakar, S. Lale","doi":"10.2174/2210303113666230622123933","DOIUrl":"https://doi.org/10.2174/2210303113666230622123933","url":null,"abstract":"\u0000\u0000The development of safe and biocompatible nanoparticles has always been a major concern in nanomedicine applications. Various studies on the size-dependent toxicity of nanoparticles have been reported but are still controversial. The potential of small-sized nanoparticles can be utilized for imaging and diagnostics. However, insufficient toxicity data on these nanoparticles prevents researchers from utilizing their potential in diagnostics. More studies are needed on the toxicity of small-sized nanoparticles to present unanimous report for safe systemic use. The present study aimed to investigate the toxicity concerns of very small-sized AuNPs (2±0.5 nm, 5±1 nm, and 10±2 nm) and provide a platform for their safe in vivo use.\u0000\u0000\u0000\u0000The cellular interactions of these three small-sized AuNPs with regard to cytotoxicity were investigated on hepatocellular carcinoma (HepG2) and epithelial kidney (HEK-293) cell lines. The cytotoxicity investigation of both cell lines was done through MTT assays, PI & DAPI, and cytology. Cellular stress was investigated by Catalase, TBARS, GSH, SOD & ROS parameters. The AuNPs incubated cells were also assessed for immunogenicity by ELISA, protein interaction by BSA, and cellular internalization by TEM (Edax).\u0000\u0000\u0000\u0000All three-sized AuNPs were not toxic on cell viability, apoptosis, necrosis, or cytology assessment. No oxidative stress was noted in both cell types in the presence of 2 and 5-nm-sized AuNPs, whereas 10 nm-sized AuNPs showed little oxidative stress. AuNPs of size 2 and 5 nm were immunologically inert, but 10 nm-sized AuNPs elicited interleukin (IL-4 and IL-10) and interferon IFN gamma response. AuNPs of sized 2 nm showed 4 times the adsorption of albumin protein as compared to AuNPs of sized 5 nm. The TEM micrographs and peak of gold in the Edax graph confirmed the presence of AuNPs in cells.\u0000\u0000\u0000\u0000Our results are suggestive of utilizing the potential of these three-sized AuNPs safely in preclinical drug delivery applications.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42970208","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 : 2023-06-07DOI: 10.2174/2210303113666230607151339
Gabriela Zimmermann Prado Rodrigues, Cassiana Bigolin, Andriele Veiverberg, Ana Letícia Hilário Garcia, Juliana Machado Kayser, Fernando Bertoldi, Marcelo Dutra Arbo, Marina Galdino Pitta, I. da Rocha Pitta, G. Gehlen, Andresa Heemann Betti
The PT-31 molecule, a potential antipsychotic, has demonstrated promising results when orally administrated to in vivo models. A recent study suggested the genotoxic and mutagenic potential of PT-31 after acute treatment by intraperitoneal route. This study aimed to evaluate PT-31 potential of inducing genotoxic or mutagenic damage after acute oral administration. For that, adult males and females Balb/C mice were treated acutely by oral administration with vehicle or PT-31 in three different doses (10, 20, and 40 mg kg-1). After 24 hours from PT-31 administration, animals were euthanized for performing the comet and micronucleus assays. None of the tested groups of PT-31 presented a significant increase in damage index and MN frequency. However, they presented the following tendency on damage index: females presented a tendency at 40 mg kg-1 and males at 20 mg kg-1. Regarding the MN assay, male mice at the highest dose of 40 mg kg-1 presented a tendency of increased MN frequency. Also, there was a significant increase in PCE/NCE ratio in male mice. Results suggest that the male mice group presented higher susceptibility to damage. The tendency of increased damage to DNA and MN frequency suggests that the molecule PT-31 may induce reparable damage to DNA, and these DNA strand repairs may have originated from the MN. However, significant genotoxic and mutagenic effects were not observed. This study reinforces the atypicality of the molecule as much as its safety by oral route administration.
{"title":"Genotoxic And Mutagenic Assessment Of A Pt-31 Molecule With Antipsychotic Potential","authors":"Gabriela Zimmermann Prado Rodrigues, Cassiana Bigolin, Andriele Veiverberg, Ana Letícia Hilário Garcia, Juliana Machado Kayser, Fernando Bertoldi, Marcelo Dutra Arbo, Marina Galdino Pitta, I. da Rocha Pitta, G. Gehlen, Andresa Heemann Betti","doi":"10.2174/2210303113666230607151339","DOIUrl":"https://doi.org/10.2174/2210303113666230607151339","url":null,"abstract":"\u0000\u0000The PT-31 molecule, a potential antipsychotic, has demonstrated promising results when orally administrated to in vivo models. A recent study suggested the genotoxic and mutagenic potential of PT-31 after acute treatment by intraperitoneal route. This study aimed to evaluate PT-31 potential of inducing genotoxic or mutagenic damage after acute oral administration. For that, adult males and females Balb/C mice were treated acutely by oral administration with vehicle or PT-31 in three different doses (10, 20, and 40 mg kg-1). After 24 hours from PT-31 administration, animals were euthanized for performing the comet and micronucleus assays. None of the tested groups of PT-31 presented a significant increase in damage index and MN frequency. However, they presented the following tendency on damage index: females presented a tendency at 40 mg kg-1 and males at 20 mg kg-1. Regarding the MN assay, male mice at the highest dose of 40 mg kg-1 presented a tendency of increased MN frequency. Also, there was a significant increase in PCE/NCE ratio in male mice. Results suggest that the male mice group presented higher susceptibility to damage. The tendency of increased damage to DNA and MN frequency suggests that the molecule PT-31 may induce reparable damage to DNA, and these DNA strand repairs may have originated from the MN. However, significant genotoxic and mutagenic effects were not observed. This study reinforces the atypicality of the molecule as much as its safety by oral route administration.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43574081","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 : 2023-05-02DOI: 10.2174/2210303113666230502104226
A. Nanda, R. Kadian
The goal of this research was to formulate and optimize a cost-effective self-emulsifying drug delivery system (SEDDS) of cilnidipine to increase its dissolution rate. Cilni-dipine is a BCS class II active pharmaceutical ingredient, which limits its use. Cilnidipine's solubility in various oils, surfactants, and cosurfactants, has been investigat-ed. To determine if there is any interaction between cilnidipine and certain excipients, drug compat-ibility tests were carried out. Based on phase solubility and compatibility studies, two combinations (Canola oil, Tween 80, and PEG 300; Peanut oil, Cremophor EL, and PEG 200) were prepared to create ternary phase diagrams for selecting the best combination with higher microemulsion region and to identify the range of concentration of excipients. Cilnidipine-loaded-SEDDS formulation was prepared by incorporating Canola oil, Tween 80, and PEG 300. For achieving the best formula-tion, D-optimal mixture design was used. The optimized SEDDS formulation was evaluated for globule size, zeta potential, drug release, drug content, self-emulsification time, and stability stud-ies. The zeta potential (Y1) and globule size (Y2) of the optimized SEDDS formulation were found to be -36mV and 124.3nm, respectively. The optimized SEDDS formulation showed more than 98% drug release within 15 min in 10% ethanolic 0.1N HCl media, which was significantly higher than that of the pure drug (7.5%) and marketed tablet (~21%). The optimized formulation's self-emulsification time, drug content, and cloud point were 55s, 99.97 ± 1.57 %, and 75.6℃, re-spectively. After stability studies, there was no evidence of phase separation, colour change, and change in globule size. A significant improvement in in vitro drug release was observed from cilnidipine-loaded-SEDDS.
{"title":"Formulation, Optimization, and In vitro Characterization of Cilnidipine-loaded Self-emulsifying Drug Delivery System","authors":"A. Nanda, R. Kadian","doi":"10.2174/2210303113666230502104226","DOIUrl":"https://doi.org/10.2174/2210303113666230502104226","url":null,"abstract":"\u0000\u0000The goal of this research was to formulate and optimize a cost-effective self-emulsifying drug delivery system (SEDDS) of cilnidipine to increase its dissolution rate. Cilni-dipine is a BCS class II active pharmaceutical ingredient, which limits its use.\u0000\u0000\u0000\u0000Cilnidipine's solubility in various oils, surfactants, and cosurfactants, has been investigat-ed. To determine if there is any interaction between cilnidipine and certain excipients, drug compat-ibility tests were carried out. Based on phase solubility and compatibility studies, two combinations (Canola oil, Tween 80, and PEG 300; Peanut oil, Cremophor EL, and PEG 200) were prepared to create ternary phase diagrams for selecting the best combination with higher microemulsion region and to identify the range of concentration of excipients. Cilnidipine-loaded-SEDDS formulation was prepared by incorporating Canola oil, Tween 80, and PEG 300. For achieving the best formula-tion, D-optimal mixture design was used. The optimized SEDDS formulation was evaluated for globule size, zeta potential, drug release, drug content, self-emulsification time, and stability stud-ies.\u0000\u0000\u0000\u0000The zeta potential (Y1) and globule size (Y2) of the optimized SEDDS formulation were found to be -36mV and 124.3nm, respectively. The optimized SEDDS formulation showed more than 98% drug release within 15 min in 10% ethanolic 0.1N HCl media, which was significantly higher than that of the pure drug (7.5%) and marketed tablet (~21%). The optimized formulation's self-emulsification time, drug content, and cloud point were 55s, 99.97 ± 1.57 %, and 75.6℃, re-spectively. After stability studies, there was no evidence of phase separation, colour change, and change in globule size.\u0000\u0000\u0000\u0000A significant improvement in in vitro drug release was observed from cilnidipine-loaded-SEDDS.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49168849","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 : 2023-05-02DOI: 10.2174/2210303113666230502150257
Madhu Verma, A. Nanda, Iti Chauhan, M. Yasir, Sagarika Majhi, Rajkumari, M. Sharma
SIM is a poorly water-soluble drug with dissolution-dependent bioavailability. A solid dispersion and self-emulsifying drug delivery system was developed, optimized, and evaluated to improve its bioavailability. The permeability coefficient in rats was determined using the in-situ single-pass intestinal perfusion (SPIP) technique. Further, the permeability coefficient (Peff, humans) was used to calculate the permeability and fraction of SIM bioavailable to humans which have not yet been reported for these formulations. To estimate and compare various formulations of Simvastatin (SIM) for bioavailable fraction to humans (Fa) as a function of solubility enhancement. In this study, the preparation and evaluation of SIM formulations i.e., Self-emulsifying drug delivery system (SEDDS) and Solid dispersions (SD) are discussed in brief. An uncomplicated, precise, and accurate HPLC method was validated for simultaneous determination of SIM and phenol red as per ICH guidelines. A comparative in-vitro dissolution test, pharmacokinetic studies, and in-situ SPIP technique in rats were carried out amongst optimized formulations of SIM-SD and SIM-SEDDS, SIM suspension (SIM-SUSP), and SIM marketed preparation (SIM-MP). The HPLC method was successfully validated. In-vitro dissolution test displays that both the SIM formulations i.e., SIM-SEDDS and SIM-SD shows better dissolution rate than SIM-MP and SIM-SUSP. Pharmacokinetic studies revealed that SIM-SEDDS, SIM-SD, and SIM-MP showed significant differences when compared to SIM-SUSP in terms of Cmax, [AUC] 0-∞, at P ≤ 0.05. The comparison of permeability coefficient between SIM SEDDS vs SIM MP and SIM SEDDS vs SIM SD were non-significant. In contrast, SIM- SUSP vs all other formulations were significantly different at P ≤ 0.05 (employing two-way ANOVA followed by post-Bonferroni Test). Fa for SIM SUSP, an optimized formulation of SIM-SEDDS, SIM-MP, and SIM-SD are 0.353, 0.977, 0.975, and 0.987 respectively. It is revealed that SIM-SEDDS and SIM-SD showed enhanced absorption and the results are confirmed by in-vitro data, pharmacokinetic studies, and In-situ SPIP techniques. The permeability prediction method is a rapid and economical method for screening chemical compounds with the least possible utilization of resources. So, its use can be extended in prime and initial screening prototypes for the evaluation of compounds in the early stages of their formulations.
{"title":"Estimation of human oral fraction dose absorbed of simvastatin from various formulations using in-situ single pass intestinal perfusion method","authors":"Madhu Verma, A. Nanda, Iti Chauhan, M. Yasir, Sagarika Majhi, Rajkumari, M. Sharma","doi":"10.2174/2210303113666230502150257","DOIUrl":"https://doi.org/10.2174/2210303113666230502150257","url":null,"abstract":"\u0000\u0000SIM is a poorly water-soluble drug with dissolution-dependent bioavailability. A solid dispersion and self-emulsifying drug delivery system was developed, optimized, and evaluated to improve its bioavailability. The permeability coefficient in rats was determined using the in-situ single-pass intestinal perfusion (SPIP) technique. Further, the permeability coefficient (Peff, humans) was used to calculate the permeability and fraction of SIM bioavailable to humans which have not yet been reported for these formulations.\u0000\u0000\u0000\u0000To estimate and compare various formulations of Simvastatin (SIM) for bioavailable fraction to humans (Fa) as a function of solubility enhancement.\u0000\u0000\u0000\u0000In this study, the preparation and evaluation of SIM formulations i.e., Self-emulsifying drug delivery system (SEDDS) and Solid dispersions (SD) are discussed in brief. An uncomplicated, precise, and accurate HPLC method was validated for simultaneous determination of SIM and phenol red as per ICH guidelines. A comparative in-vitro dissolution test, pharmacokinetic studies, and in-situ SPIP technique in rats were carried out amongst optimized formulations of SIM-SD and SIM-SEDDS, SIM suspension (SIM-SUSP), and SIM marketed preparation (SIM-MP).\u0000\u0000\u0000\u0000The HPLC method was successfully validated. In-vitro dissolution test displays that both the SIM formulations i.e., SIM-SEDDS and SIM-SD shows better dissolution rate than SIM-MP and SIM-SUSP. Pharmacokinetic studies revealed that SIM-SEDDS, SIM-SD, and SIM-MP showed significant differences when compared to SIM-SUSP in terms of Cmax, [AUC] 0-∞, at P ≤ 0.05. The comparison of permeability coefficient between SIM SEDDS vs SIM MP and SIM SEDDS vs SIM SD were non-significant. In contrast, SIM- SUSP vs all other formulations were significantly different at P ≤ 0.05 (employing two-way ANOVA followed by post-Bonferroni Test). Fa for SIM SUSP, an optimized formulation of SIM-SEDDS, SIM-MP, and SIM-SD are 0.353, 0.977, 0.975, and 0.987 respectively. It is revealed that SIM-SEDDS and SIM-SD showed enhanced absorption and the results are confirmed by in-vitro data, pharmacokinetic studies, and In-situ SPIP techniques.\u0000\u0000\u0000\u0000The permeability prediction method is a rapid and economical method for screening chemical compounds with the least possible utilization of resources. So, its use can be extended in prime and initial screening prototypes for the evaluation of compounds in the early stages of their formulations.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42759488","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 : 2023-05-01DOI: 10.2174/2210303113666230501204329
S. Chopade, Vaibhavi Jaunjalkar
Colon targeted medication delivery is a field of study for disorders including colon cancer and inflammatory bowel disease (IBD), with the goal of delivering localised therapy with minimal systemic damage. In recent decades, the global prevalence of colonic problems has increased, demanding more local treatment of colonic disorders, which will lead to the development of more effective and safe pharmaceutical regimens. When developing a formulation for colonic administration, it's critical to consider both the physiological characteristics of the colon and the environment surrounding the disease site (s). The GI tract experiences dynamic changes in motility, fluid volume, enzyme activity, and pH from the middle to the intestine. The current review focuses on Biodegradable polymers or protein‑based microspheres having free‑flowing properties and particle size 5200 nm have a variety of advantages over conventional colon targeted drug delivery systems. During drug transit through the GIT, polysaccharides maintain their integrity and inhibit drug release. When it comes into contact with colonic fluid, however, it is attacked by anaerobic microbes, and the imprisoned medication is released. In this review, several methods of microsphere formulation and characterization were investigated along with its in vitro and in vivo study methodology.
{"title":"Microspheres: A Novel approach for Sustained Colon Targeted Drug Delivery","authors":"S. Chopade, Vaibhavi Jaunjalkar","doi":"10.2174/2210303113666230501204329","DOIUrl":"https://doi.org/10.2174/2210303113666230501204329","url":null,"abstract":"\u0000\u0000Colon targeted medication delivery is a field of study for disorders including colon cancer and inflammatory bowel disease (IBD), with the goal of delivering localised therapy with minimal systemic damage. In recent decades, the global prevalence of colonic problems has increased, demanding more local treatment of colonic disorders, which will lead to the development of more effective and safe pharmaceutical regimens. When developing a formulation for colonic administration, it's critical to consider both the physiological characteristics of the colon and the environment surrounding the disease site (s). The GI tract experiences dynamic changes in motility, fluid volume, enzyme activity, and pH from the middle to the intestine. The current review focuses on Biodegradable polymers or protein‑based microspheres having free‑flowing properties and particle size 5200 nm have a variety of advantages over conventional colon targeted drug delivery systems. During drug transit through the GIT, polysaccharides maintain their integrity and inhibit drug release. When it comes into contact with colonic fluid, however, it is attacked by anaerobic microbes, and the imprisoned medication is released. In this review, several methods of microsphere formulation and characterization were investigated along with its in vitro and in vivo study methodology.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44388382","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 : 2023-04-07DOI: 10.2174/2210303113666230407082515
M. Athalye, Dolly N. Vachheta, Y. Shah, Drashty K. Kakkad, Mansi J. Darji
This review aims to provide historical, present, and future drug deliveries for treating inner ear disorders. Systemic delivery, such as antibiotics and steroids for the inner ear, was the basis on which current drug delivery systems and devices have been researched and developed. Researchers and clinicians had to develop and deliver drugs locally due to adverse effects caused by drugs systemically. Intratympanic method of antibiotics and steroid delivery has been common; however, newer techniques such as microcatheter implantation, hydrogels, nanoparticles, and intracochlear implants are being investigated successfully. Recently advances in microfluidic and microsystems technology have applied medications directly into the inner ear. This technology will also be adopted to deliver gene therapy, RNA interference technology, and stem cell therapy by clinicians in the future.
{"title":"Treating Sensorineural Hearing Loss: Recent Advances in Inner Ear Drug\u0000Delivery","authors":"M. Athalye, Dolly N. Vachheta, Y. Shah, Drashty K. Kakkad, Mansi J. Darji","doi":"10.2174/2210303113666230407082515","DOIUrl":"https://doi.org/10.2174/2210303113666230407082515","url":null,"abstract":"\u0000\u0000This review aims to provide historical, present, and future drug deliveries for treating inner ear disorders. Systemic delivery, such as antibiotics and steroids for the inner ear, was the basis\u0000on which current drug delivery systems and devices have been researched and developed. Researchers and clinicians had to develop and deliver drugs locally due to adverse effects caused by\u0000drugs systemically. Intratympanic method of antibiotics and steroid delivery has been common;\u0000however, newer techniques such as microcatheter implantation, hydrogels, nanoparticles, and intracochlear implants are being investigated successfully. Recently advances in microfluidic and microsystems technology have applied medications directly into the inner ear. This technology will\u0000also be adopted to deliver gene therapy, RNA interference technology, and stem cell therapy by clinicians in the future.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41649567","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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