Pub Date : 2019-05-31DOI: 10.2174/2210303109666181224115722
Benedita Kaç Labbé Feron, S. Richardson
The design of advanced drug delivery systems based on synthetic and supramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein, the use of synthetic proteins for drug delivery has been reviewed.
{"title":"The Delivery of Personalised, Precision Medicines via Synthetic Proteins","authors":"Benedita Kaç Labbé Feron, S. Richardson","doi":"10.2174/2210303109666181224115722","DOIUrl":"https://doi.org/10.2174/2210303109666181224115722","url":null,"abstract":"\u0000\u0000The design of advanced drug delivery systems based on synthetic and supramolecular\u0000chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal\u0000daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible\u0000polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable\u0000achievements.\u0000\u0000\u0000\u0000As deliverables have evolved from low molecular weight drugs to biologics (currently representing\u0000approximately 30% of the market), so too have the demands made of advanced drug delivery\u0000technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking\u0000of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein\u0000toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant\u0000proteins provides several possibilities.\u0000\u0000\u0000\u0000The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or\u0000agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach\u0000targets that are not normally accessible. This may be achieved by grafting regulatory domains from\u0000multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to\u0000the nucleocytosolic compartment. Herein, the use of synthetic proteins for drug delivery has been\u0000reviewed.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41330207","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 : 2019-05-31DOI: 10.2174/2210303109666190212112505
Deep Kumar
The main objective of the study was to develop gliptin loaded polymeric nanomicelles by direct dissolution method. The comparative evaluation studies were performed to study the effect of polymer concentration on particle size, entrapment efficiency, loading capacity and drug release of the formulation. Gliptin loaded polymeric nanomicelles were prepared by the direct dissolution method. The formulations were prepared by varying the concentration of polymer and drug concentration was kept constant in all the formulations. The concentration of polymer (pullulan) was maintained 0.1%, 0.5% 1% in formulation F-1, F-2 and F-3, respectively. The effect of polymer concentration on mean particle size, zeta potential, % entrapment efficiency, % loading capacity and in vitro drug release was studied. The optimized nanoformulation was obtained with pullulan 0.1% concentration with a mean particle diameter of 368.2nm and zeta potential value (-7.96mV) indicating greater stability. Hence F-1 was considered to be the best formulation for the preparation of gliptin loaded polymeric nanomicelles. Hence, it can be concluded that polymeric nanomicellar approach can be beneficial to improve the bioavailability and poor permeability of class III drugs like gliptins and thus can be a better approach for controlled drug delivery.
{"title":"Formulation and Evaluation of Polymeric Nanomicelles of Gliptin for Controlled Drug Delivery","authors":"Deep Kumar","doi":"10.2174/2210303109666190212112505","DOIUrl":"https://doi.org/10.2174/2210303109666190212112505","url":null,"abstract":"\u0000\u0000The main objective of the study was to develop gliptin loaded polymeric\u0000nanomicelles by direct dissolution method. The comparative evaluation studies were performed to study\u0000the effect of polymer concentration on particle size, entrapment efficiency, loading capacity and drug\u0000release of the formulation.\u0000\u0000\u0000\u0000Gliptin loaded polymeric nanomicelles were prepared by the direct dissolution method. The\u0000formulations were prepared by varying the concentration of polymer and drug concentration was kept\u0000constant in all the formulations. The concentration of polymer (pullulan) was maintained 0.1%, 0.5%\u00001% in formulation F-1, F-2 and F-3, respectively. The effect of polymer concentration on mean particle\u0000size, zeta potential, % entrapment efficiency, % loading capacity and in vitro drug release was studied.\u0000\u0000\u0000\u0000The optimized nanoformulation was obtained with pullulan 0.1% concentration with a mean\u0000particle diameter of 368.2nm and zeta potential value (-7.96mV) indicating greater stability.\u0000\u0000\u0000\u0000Hence F-1 was considered to be the best formulation for the preparation of gliptin loaded\u0000polymeric nanomicelles. Hence, it can be concluded that polymeric nanomicellar approach can be beneficial\u0000to improve the bioavailability and poor permeability of class III drugs like gliptins and thus can be\u0000a better approach for controlled drug delivery.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46827301","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 : 2019-05-31DOI: 10.2174/2210303109666190118162157
A. Rani, Sunil Kumar, R. Khar
Herbal extracts have brilliant in-vitro activity but less in-vivo action in light of their macromolecular size and poor lipid solubility bringing about poor absorption and low bioavailability. These issues can be corrected by designing novel drug delivery systems. Phytosomes provide better absorption and bioavailability when compared to conventional herbal extract.This paper deals with the preparation, optimization and characterization of Phytosome of plant extract and in vivo assessment of antidiabetic and antihyperlipidemic activity for improved therapeutic efficacy having sufficient stability.Preliminary distinctive strategies were utilized to get ready Phytosome and antisolvent precipitation method was chosen. The formulation was guided by a full factorial design to study the effect of Independent variable on various dependent variables and resulted in an optimised product. Response contour plots were generated for each response factor to predict a phytosomal composition that yields phytosome formulation having least particle size and maximum entrapment efficiency.Mean particle size, entrapment efficiency and Span value were found to be 295 ± 0.53nm, 82.43 ± 1.65% and 0.34 ± 0.14 respectively. Zeta potential was found to be 19.35mv, indicating the formation of stable formulation. In vitro release study described that the drug release follows the Korsmeyer- Peppas kinetic model. The results proved that Phytosomes of Casuarina equisetifolia extract exhibited more antidiabetic potential and antihyperlipidemic properties as compared to crude Casuarina extract.Phytosomes of Casuarina equestifolia extract was successfully formulated having good entrapment efficiency and physico-chemical characterization of the optimized product, confirming the formation of stable formulation. In vivo antidiabetic activity confirmed better potential of the optimised formulation. Consequently, it has been presumed that Phytosomes of Casuarina equisetifolia extract serve as a useful novel drug delivery system and provide more therapeutic efficacy than conventional plant extracts.
{"title":"Casuarina equisetifoliaExtract Loaded Phytosomes: Optimization, Characterization andIn vivoEvaluation of Antidiabetic and Antihyperlipidemic Activities in Wistar Rats","authors":"A. Rani, Sunil Kumar, R. Khar","doi":"10.2174/2210303109666190118162157","DOIUrl":"https://doi.org/10.2174/2210303109666190118162157","url":null,"abstract":"Herbal extracts have brilliant in-vitro activity but less in-vivo action in light of their macromolecular size and poor lipid solubility bringing about poor absorption and low bioavailability. These issues can be corrected by designing novel drug delivery systems. Phytosomes provide better absorption and bioavailability when compared to conventional herbal extract.This paper deals with the preparation, optimization and characterization of Phytosome of plant extract and in vivo assessment of antidiabetic and antihyperlipidemic activity for improved therapeutic efficacy having sufficient stability.Preliminary distinctive strategies were utilized to get ready Phytosome and antisolvent precipitation method was chosen. The formulation was guided by a full factorial design to study the effect of Independent variable on various dependent variables and resulted in an optimised product. Response contour plots were generated for each response factor to predict a phytosomal composition that yields phytosome formulation having least particle size and maximum entrapment efficiency.Mean particle size, entrapment efficiency and Span value were found to be 295 ± 0.53nm, 82.43 ± 1.65% and 0.34 ± 0.14 respectively. Zeta potential was found to be 19.35mv, indicating the formation of stable formulation. In vitro release study described that the drug release follows the Korsmeyer- Peppas kinetic model. The results proved that Phytosomes of Casuarina equisetifolia extract exhibited more antidiabetic potential and antihyperlipidemic properties as compared to crude Casuarina extract.Phytosomes of Casuarina equestifolia extract was successfully formulated having good entrapment efficiency and physico-chemical characterization of the optimized product, confirming the formation of stable formulation. In vivo antidiabetic activity confirmed better potential of the optimised formulation. Consequently, it has been presumed that Phytosomes of Casuarina equisetifolia extract serve as a useful novel drug delivery system and provide more therapeutic efficacy than conventional plant extracts.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41876602","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 : 2019-05-15DOI: 10.2174/2210303109666190128151605
T. Giri, Tania Adhikary, S. Maity
The presence of capsaicin in the diet has been revealed to enhance energy expenditure and it has been used in anti-obesity therapy. The present work investigated the potential antihyperlipidemic effect of capsaicin loaded hydrogel beads on hyperlipidemic rats. Hydrogels are three dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids. Capsaicin loaded hydrogel beads were prepared by the ionotropic gelation method using Aluminium Chloride (AlCl₃) as a cross-linking agent. The characterization of hydrogel beads was carried out by X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopic (SEM) analysis. The surface morphology revealed that the prepared beads were spherical in shape. XRD and DSC study of the hydrogel beads revealed that the drug was homogeneously dispersed in the hydrogel matrix. The beads showed pH sensitive behavior and when the medium pH was changed from 1.2 to 7.4, the capsaicin release was considerably increased. 100mg/kg body weight of Triton was injected intraperitoneally in rats to induce hyperlipidemia and it showed elevated levels of serum cholesterol and triglyceride. Capsaicin loaded hydrogel beads were administered to normal and hyperlipidemic rats for 7 days and the prepared hydrogel beads were significantly reduced high lipid profile in comparison to free capsaicin. The results clearly demonstrated that hydrogel beads can be used as a potential carrier for delivery of capsaicin to reduce lipid profile.
{"title":"Development of Capsaicin Loaded Hydrogel Beads for In vivo Lipid Lowering Activities of Hyperlipidemic Rats","authors":"T. Giri, Tania Adhikary, S. Maity","doi":"10.2174/2210303109666190128151605","DOIUrl":"https://doi.org/10.2174/2210303109666190128151605","url":null,"abstract":"\u0000\u0000The presence of capsaicin in the diet has been revealed to enhance energy expenditure\u0000and it has been used in anti-obesity therapy. The present work investigated the potential antihyperlipidemic\u0000effect of capsaicin loaded hydrogel beads on hyperlipidemic rats. Hydrogels are three\u0000dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological\u0000fluids.\u0000\u0000\u0000\u0000Capsaicin loaded hydrogel beads were prepared by the ionotropic gelation method using\u0000Aluminium Chloride (AlCl₃) as a cross-linking agent. The characterization of hydrogel beads was carried\u0000out by X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), and Scanning Electron\u0000Microscopic (SEM) analysis.\u0000\u0000\u0000\u0000The surface morphology revealed that the prepared beads were spherical in shape. XRD and\u0000DSC study of the hydrogel beads revealed that the drug was homogeneously dispersed in the hydrogel\u0000matrix. The beads showed pH sensitive behavior and when the medium pH was changed from 1.2 to\u00007.4, the capsaicin release was considerably increased. 100mg/kg body weight of Triton was injected intraperitoneally\u0000in rats to induce hyperlipidemia and it showed elevated levels of serum cholesterol and\u0000triglyceride. Capsaicin loaded hydrogel beads were administered to normal and hyperlipidemic rats for\u00007 days and the prepared hydrogel beads were significantly reduced high lipid profile in comparison to\u0000free capsaicin.\u0000\u0000\u0000\u0000The results clearly demonstrated that hydrogel beads can be used as a potential carrier for\u0000delivery of capsaicin to reduce lipid profile.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46194805","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 : 2019-05-15DOI: 10.2174/2210303109666190102115814
Parth Patel, Y. Agrawal
Levans are biopolymers of fructose, produced by different microorganisms. Fructose present in the levan micelles binds with the Glucose Transporter 5 (GLUT 5) which is overexpressed in the breast cancer cells. Increased solubility of paclitaxel by loading in the GLUT 5 transporter targeted levan-based micelles may enhance its bioavailability and facilitate a targeted delivery to the breast cancer cells. Critical micelle concentration of levan with an average molecular weight of 800,000 Dalton was found to be 0.125µM corresponding to 0.1mg/mL using pyrene I3/I1 method. At critical micelle concentration (CMC), levan formed very mono-disperse (PDI-0.082) micellar particles with a particle size of 153.1 ± 2.31nm and -14.6 ± 2mV zeta potential. In-vitro drug release study was performed to identify the fit kinetic model along with Fourier transform infrared analysis and Differential scanning calorimetry studies. In-vitro kinetic model fitting revealed first-order drug release from the prepared micellar composition. The drug-loaded micellar composition was studied for its anticancer activity in breast cancer cell line. The IC50 value obtained was 1.525 ± 0.11nM on MCF7 cell line. Paclitaxel micelles showed a nineteen-fold improvement in the IC50 value compared to free paclitaxel. Hemocompatibility study was performed with a view to parenteral administration. This solution containing drug was found to be hemocompatible when added to bovine blood in 1:4 ration. Micelles are proven fairly compatible on the basis of hemolysis test results.
{"title":"Preparation and In-vitro Evaluation of Levan Micelles: A Polyfructan Based Nano-carrier for Breast Cancer Targeted Delivery","authors":"Parth Patel, Y. Agrawal","doi":"10.2174/2210303109666190102115814","DOIUrl":"https://doi.org/10.2174/2210303109666190102115814","url":null,"abstract":"\u0000\u0000Levans are biopolymers of fructose, produced by different microorganisms.\u0000Fructose present in the levan micelles binds with the Glucose Transporter 5 (GLUT 5) which is overexpressed\u0000in the breast cancer cells.\u0000\u0000\u0000\u0000Increased solubility of paclitaxel by loading in the GLUT 5 transporter targeted levan-based\u0000micelles may enhance its bioavailability and facilitate a targeted delivery to the breast cancer cells.\u0000\u0000\u0000\u0000Critical micelle concentration of levan with an average molecular weight of\u0000800,000 Dalton was found to be 0.125µM corresponding to 0.1mg/mL using pyrene I3/I1 method. At\u0000critical micelle concentration (CMC), levan formed very mono-disperse (PDI-0.082) micellar particles\u0000with a particle size of 153.1 ± 2.31nm and -14.6 ± 2mV zeta potential. In-vitro drug release study was\u0000performed to identify the fit kinetic model along with Fourier transform infrared analysis and Differential\u0000scanning calorimetry studies. In-vitro kinetic model fitting revealed first-order drug release from\u0000the prepared micellar composition. The drug-loaded micellar composition was studied for its anticancer\u0000activity in breast cancer cell line. The IC50 value obtained was 1.525 ± 0.11nM on MCF7 cell line.\u0000\u0000\u0000\u0000Paclitaxel micelles showed a nineteen-fold improvement in the IC50 value compared to\u0000free paclitaxel. Hemocompatibility study was performed with a view to parenteral administration. This\u0000solution containing drug was found to be hemocompatible when added to bovine blood in 1:4 ration.\u0000Micelles are proven fairly compatible on the basis of hemolysis test results.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46661821","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 : 2019-05-15DOI: 10.2174/2210303109666190211150117
A. Sailaja, J. Banu
The aim of this investigation was to develop and characterize naproxen loaded chitosan nanoparticles by emulsion interfacial reaction method. For emulsion interfacial reaction method chitosan was used as a polymer. In this method, eight formulations were prepared by varying drug to polymer concentration. Out of eight formulations prepared using emulsion interfacial reaction method EI8 formulation was found to be the best formulation. The drug content was observed as 94.4%, entrapment efficiency and loading capacity were found to be 87.5% and 75%, respectively. The mean particle diameter was measured as 324.6nm and the Zeta potential value was found to be -42.4mv. In vitro drug release data showed 97.2% of drug release rate sustained up to 12hrs. The results clearly reveal that EI8 formulation having the highest amount of drug was considered as the best formulation because of its small mean particle diameter, good entrapment efficiency, and stability.
{"title":"Preparation and Evaluation of Chitosan Loaded Naproxen Nanoparticles by Emulsion Interfacial Reaction Method","authors":"A. Sailaja, J. Banu","doi":"10.2174/2210303109666190211150117","DOIUrl":"https://doi.org/10.2174/2210303109666190211150117","url":null,"abstract":"\u0000\u0000The aim of this investigation was to develop and characterize naproxen loaded chitosan\u0000nanoparticles by emulsion interfacial reaction method.\u0000\u0000\u0000\u0000For emulsion interfacial reaction method chitosan was used as a polymer. In this\u0000method, eight formulations were prepared by varying drug to polymer concentration.\u0000\u0000\u0000\u0000Out of eight formulations prepared using emulsion interfacial reaction method EI8 formulation\u0000was found to be the best formulation. The drug content was observed as 94.4%, entrapment efficiency\u0000and loading capacity were found to be 87.5% and 75%, respectively. The mean particle diameter\u0000was measured as 324.6nm and the Zeta potential value was found to be -42.4mv. In vitro drug release\u0000data showed 97.2% of drug release rate sustained up to 12hrs.\u0000\u0000\u0000\u0000The results clearly reveal that EI8 formulation having the highest amount of drug was\u0000considered as the best formulation because of its small mean particle diameter, good entrapment efficiency,\u0000and stability.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41481907","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 : 2019-02-28DOI: 10.2174/2210303108666180903102107
Fanni Farner, L. Bors, Ágnes Bajza, G. Karvaly, I. Antal, F. Erdő
Introduction: Degree of skin penetration of topical drugs and cosmetics is a crucial point concerning their effects and tolerability. For testing drug delivery across the dermal barrier different in vitro and in vivo assays have been developed. Caffeine has been shown to have beneficial effects against skin aging, sunburn and hair-loss, and it is protective against melanoma and non-melanoma type skin cancers. Aim of our study was to set up an assay system to evaluate caffeine penetration from topical formulation into the skin. Methods: Franz diffusion cells consisting of either a filter paper or an artificial membrane or rat skin were used as in vitro/ex vivo test systems and transdermal microdialysis in anaesthetized rats was performed as an in vivo assay. Results: Results indicate that Franz diffusion cell studies provide a good approximation of the release of caffeine from the formulation but are not able to differentiate between 2% and 4% cream concentrations. The maximum concentrations (Cmax) in case of the 2% cream formulation were 708.3 (2.7 μm pore), 78.7 (0.8 µm pore), 45.3 (0.45 µm pore) and 44.9 (rat skin) µg/7.5 mL, respectively. The in vivo microdialysis experiments were in accordance with the in vitro and ex vivo results and gave more information on the dynamics and follicular and transcellular phases of drug penetration through the layers of the skin. Discussion and Conclusion: Taken together, Franz diffusion cell and transdermal microdialysis are a good combination to evaluate caffeine release and penetration into the skin from the formulations tested. This system might also be used for rapid testing of other hydrophilic topical drugs and has a benefit in the prediction for human skin absorption and tolerability studies, in an early phase of drug development.
{"title":"Validation of an In vitro-in vivo Assay System for Evaluation of Transdermal Delivery of Caffeine","authors":"Fanni Farner, L. Bors, Ágnes Bajza, G. Karvaly, I. Antal, F. Erdő","doi":"10.2174/2210303108666180903102107","DOIUrl":"https://doi.org/10.2174/2210303108666180903102107","url":null,"abstract":"\u0000\u0000Introduction: Degree of skin penetration of topical drugs and cosmetics is a crucial point\u0000concerning their effects and tolerability. For testing drug delivery across the dermal barrier different in\u0000vitro and in vivo assays have been developed. Caffeine has been shown to have beneficial effects\u0000against skin aging, sunburn and hair-loss, and it is protective against melanoma and non-melanoma\u0000type skin cancers. Aim of our study was to set up an assay system to evaluate caffeine penetration from\u0000topical formulation into the skin.\u0000\u0000Methods: Franz diffusion cells consisting of either a filter paper or an artificial membrane or rat skin\u0000were used as in vitro/ex vivo test systems and transdermal microdialysis in anaesthetized rats was performed\u0000as an in vivo assay.\u0000\u0000Results: Results indicate that Franz diffusion cell studies provide a good approximation of the release\u0000of caffeine from the formulation but are not able to differentiate between 2% and 4% cream concentrations.\u0000The maximum concentrations (Cmax) in case of the 2% cream formulation were 708.3 (2.7 μm\u0000pore), 78.7 (0.8 µm pore), 45.3 (0.45 µm pore) and 44.9 (rat skin) µg/7.5 mL, respectively. The in vivo\u0000microdialysis experiments were in accordance with the in vitro and ex vivo results and gave more information\u0000on the dynamics and follicular and transcellular phases of drug penetration through the layers\u0000of the skin.\u0000\u0000Discussion and Conclusion: Taken together, Franz diffusion cell and transdermal microdialysis are a\u0000good combination to evaluate caffeine release and penetration into the skin from the formulations\u0000tested. This system might also be used for rapid testing of other hydrophilic topical drugs and has a\u0000benefit in the prediction for human skin absorption and tolerability studies, in an early phase of drug\u0000development.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2210303108666180903102107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41917169","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 : 2019-02-28DOI: 10.2174/2210303108666181120110756
Sunil K. Jain, K. Patel, Kuldeep Rajpoot, A. Jain
Background and Objective: The H. pylori infection causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. Infection with H. pylori is the well-known risk factor for gastric cancer. It is highly desirable to develop a delivery system that localizes the antibiotic at the site of infection to achieve bactericidal concentration for a longer period of time. Thus, present work aimed to develop Concanavalin-A (Con-A) conjugated gastro-retentive microspheres of polymethylmethacrylate (PMMA) and polyethylene oxide (PEO) containing berberine hydrochloride (BBR) for the treatment of H. pylori infection. Methods: Microspheres were prepared by solvent evaporation method and characterized by particles size distribution, surface morphology, % drug entrapment and in vitro drug release in the simulated gastric fluid. Optimized microspheres were conjugated with Con-A and further characterized for Con-A conjugation efficiency, in vitro drug release and ex vivo mucoadhesive properties. Results and Conclusion: Enhanced mucoadhesion (88±1.9%) was shown by Con-A conjugated microspheres as compared with non-conjugated microspheres (14.5±3.6%). This significant difference (p<0.05) in the mucoadhesion may be due to affinity of the Con-A towards glycoproteins of mucus membrane of stomach. Attachment of lectin (Con-A) to the microspheres significantly enhanced the mucoadhesiveness as well as also controlled the berberine release for 10 h study period. The preliminary results from this study advised that Con-A conjugated PMMA and PEO microspheres could be used to incorporate some more herbal drugs and may be used for oral administration against H. pylori in the stomach.
{"title":"Development of a Berberine Loaded Multifunctional Design for the Treatment of Helicobacter pylori Induced Gastric Ulcer","authors":"Sunil K. Jain, K. Patel, Kuldeep Rajpoot, A. Jain","doi":"10.2174/2210303108666181120110756","DOIUrl":"https://doi.org/10.2174/2210303108666181120110756","url":null,"abstract":"\u0000\u0000Background and Objective: The H. pylori infection causes chronic inflammation and significantly\u0000increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. Infection\u0000with H. pylori is the well-known risk factor for gastric cancer. It is highly desirable to develop a\u0000delivery system that localizes the antibiotic at the site of infection to achieve bactericidal concentration\u0000for a longer period of time. Thus, present work aimed to develop Concanavalin-A (Con-A) conjugated\u0000gastro-retentive microspheres of polymethylmethacrylate (PMMA) and polyethylene oxide (PEO) containing\u0000berberine hydrochloride (BBR) for the treatment of H. pylori infection.\u0000\u0000Methods: Microspheres were prepared by solvent evaporation method and characterized by particles\u0000size distribution, surface morphology, % drug entrapment and in vitro drug release in the simulated gastric\u0000fluid. Optimized microspheres were conjugated with Con-A and further characterized for Con-A\u0000conjugation efficiency, in vitro drug release and ex vivo mucoadhesive properties.\u0000\u0000Results and Conclusion: Enhanced mucoadhesion (88±1.9%) was shown by Con-A conjugated microspheres\u0000as compared with non-conjugated microspheres (14.5±3.6%). This significant difference\u0000(p<0.05) in the mucoadhesion may be due to affinity of the Con-A towards glycoproteins of mucus\u0000membrane of stomach. Attachment of lectin (Con-A) to the microspheres significantly enhanced the\u0000mucoadhesiveness as well as also controlled the berberine release for 10 h study period. The preliminary\u0000results from this study advised that Con-A conjugated PMMA and PEO microspheres could be\u0000used to incorporate some more herbal drugs and may be used for oral administration against H. pylori in\u0000the stomach.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42478223","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 : 2019-02-28DOI: 10.2174/2210303109666181224114546
Sambhaji R. Bamane and Vijay J. Sawant
Destroying hydrophobicity and increasing bioavailability of anticancer drugs is emerging field in biomedical nanotherapy. Methods: The porous and oval shaped Gd2O3 gadolinite nanoparticles were synthesized and surface functionalized with folate groups using wet coprecipitation method. The presence of spinal nanophase with Gd2O3 lattice inside nanoparticles was confirmed by the use of XRD pattern and supportive FTIR spectrum. XRD data of nanocomposites proved the spinal core of gadolinite phase even after surface tailoring. These porous nanoparticles were loaded with anticancer drug 5-flurouracil for enhancement of anticancer activity on breast cancer MCF-7 cells. The elemental, optical, morphological and phase physicochemical characterization of the nanomaterials were performed using techniques such as PL, FTIR, XRD spectrometry, TGA thermal analysis, SEM and TEM microscopic analysis. The photoactive biocompatibility of nanohybrids was elaborated on gram positive S. aureus bacteria by agar well antibacterial screening in dark and light. Results: The nanocomposites not only exhibited photoactive biocompatibility but also pH responsive in vitro delivery applied for anticancer therapy on the basis of spectrometric assay following sustained release with zero order Peppas release kinetics. The nanocomposites exhibited higher anticancer activity on MCF-7 cells than free drug and nanohybrids after in vitro MTT assay. These 5-FU loaded folate targeted luminescent and photoactive nanocomposites with gadolinite core find applications in the future biomedical cell-particle interface.
{"title":"Folate Tethered Gd2O3 Nanoparticles Exhibit Photoactive Antimicrobial Effects and pH Responsive Delivery of 5-fluorouracil into MCF-7 Cells","authors":"Sambhaji R. Bamane and Vijay J. Sawant","doi":"10.2174/2210303109666181224114546","DOIUrl":"https://doi.org/10.2174/2210303109666181224114546","url":null,"abstract":"\u0000\u0000 Destroying hydrophobicity and increasing bioavailability of anticancer drugs\u0000is emerging field in biomedical nanotherapy.\u0000\u0000Methods: The porous and oval shaped Gd2O3 gadolinite nanoparticles were synthesized and surface\u0000functionalized with folate groups using wet coprecipitation method. The presence of spinal nanophase\u0000with Gd2O3 lattice inside nanoparticles was confirmed by the use of XRD pattern and supportive FTIR\u0000spectrum. XRD data of nanocomposites proved the spinal core of gadolinite phase even after surface\u0000tailoring. These porous nanoparticles were loaded with anticancer drug 5-flurouracil for enhancement\u0000of anticancer activity on breast cancer MCF-7 cells. The elemental, optical, morphological and phase\u0000physicochemical characterization of the nanomaterials were performed using techniques such as PL,\u0000FTIR, XRD spectrometry, TGA thermal analysis, SEM and TEM microscopic analysis. The photoactive\u0000biocompatibility of nanohybrids was elaborated on gram positive S. aureus bacteria by agar well\u0000antibacterial screening in dark and light.\u0000\u0000Results: The nanocomposites not only exhibited photoactive biocompatibility but also pH responsive in\u0000vitro delivery applied for anticancer therapy on the basis of spectrometric assay following sustained release\u0000with zero order Peppas release kinetics.\u0000\u0000\u0000\u0000 The nanocomposites exhibited higher anticancer activity on MCF-7 cells than free drug\u0000and nanohybrids after in vitro MTT assay. These 5-FU loaded folate targeted luminescent and photoactive\u0000nanocomposites with gadolinite core find applications in the future biomedical cell-particle interface.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68161336","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 : 2019-02-06DOI: 10.2174/2210303109666181203150830
Bijaya Ghosh, Niraj Mishra, Preeta Bose, Moumita Das Kirtania
Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and stiffness of joints, leading to severe immobility problems. The disease shows circadian variation and usually gets aggravated in early morning hours. Aceclofenac, a BCS Class II compound is routinely used in the treatment of pain and inflammation associated with rheumatoid arthritis. The objective of this study was to develop an osmotic delivery system of Aceclofenac that after administration at bedtime would deliver the drug in the morning hours. Methods: A series of osmotically controlled systems of aceclofenac was developed by using lactose, sodium chloride and hydroxypropyl methylcellulose K100M as osmogens. Cellulose acetate (2% w/v in acetone) with varying concentrations of polyethylene glycol-400 was used as the coating polymer to create semi permeable membrane and dissolution was carried out in 290 mOsm phosphate buffer. Formulation optimization was done from four considerations: cumulative release at the end of 6 hours (lag time), cumulative release at the end of 7 hours (burst time), steady state release rate and completeness of drug release. Results: A formulation having swelling polymer hydroxypropyl methylcellulose in the core and lactose and sodium chloride as osmogens, polyethylene glycol-400 (16.39 %) as pore former, with a coating weight of 5% was a close fit to the target release profile and was chosen as the optimum formulation. Aceclofenac tablets containing lactose, HPMC and sodium chloride in the core, given a coating of cellulose acetate and PEG-400 (5% wt gain), generated a release profile for optimum management of rheumatoid arthritic pain.
{"title":"Development, Evaluation and Optimization of Osmotic Controlled Tablets of Aceclofenac for Rheumatoid Arthritis Management","authors":"Bijaya Ghosh, Niraj Mishra, Preeta Bose, Moumita Das Kirtania","doi":"10.2174/2210303109666181203150830","DOIUrl":"https://doi.org/10.2174/2210303109666181203150830","url":null,"abstract":"\u0000\u0000Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and\u0000stiffness of joints, leading to severe immobility problems. The disease shows circadian variation and\u0000usually gets aggravated in early morning hours. Aceclofenac, a BCS Class II compound is routinely\u0000used in the treatment of pain and inflammation associated with rheumatoid arthritis. The objective of\u0000this study was to develop an osmotic delivery system of Aceclofenac that after administration at\u0000bedtime would deliver the drug in the morning hours.\u0000\u0000Methods: A series of osmotically controlled systems of aceclofenac was developed by using lactose,\u0000sodium chloride and hydroxypropyl methylcellulose K100M as osmogens. Cellulose acetate (2% w/v in\u0000acetone) with varying concentrations of polyethylene glycol-400 was used as the coating polymer to\u0000create semi permeable membrane and dissolution was carried out in 290 mOsm phosphate buffer. Formulation\u0000optimization was done from four considerations: cumulative release at the end of 6 hours (lag\u0000time), cumulative release at the end of 7 hours (burst time), steady state release rate and completeness of\u0000drug release.\u0000\u0000Results: A formulation having swelling polymer hydroxypropyl methylcellulose in the core and lactose\u0000and sodium chloride as osmogens, polyethylene glycol-400 (16.39 %) as pore former, with a coating\u0000weight of 5% was a close fit to the target release profile and was chosen as the optimum formulation.\u0000\u0000\u0000\u0000 Aceclofenac tablets containing lactose, HPMC and sodium chloride in the core, given a\u0000coating of cellulose acetate and PEG-400 (5% wt gain), generated a release profile for optimum management\u0000of rheumatoid arthritic pain.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68161269","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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