Journal of pharmaceutics & drug delivery research最新文献

{"title":"Hydrogel Dressings for Chronic Wound Healing in Diabetes: Beyond Hydration.","authors":"Paul R. Hartmeier, N. Pham, K. Velankar, F. Issa, N. Giannoukakis, W. Meng","doi":"10.37532/2325-9604.2021.10(1).197","DOIUrl":"https://doi.org/10.37532/2325-9604.2021.10(1).197","url":null,"abstract":"Chronic wounds caused by diabetes are a significant medical challenge. Complications from non-healing can result in dire consequences for patients and cost the healthcare system billions of dollars annually. Non-healing in wounds for diabetic patient's results from a combination of factors which impair clearing of injured tissue, proliferation of healthy cell populations and increase risk of infection. Wound dressings continue to form the basis for the treatment of chronic wounds. Traditionally, these focused solely on hydration of the wound site and mitigating infection risk. Hydrogel systems are ready made to meet these basic requirements due to their intrinsic hydration properties and ability to deliver active ingredients. Flexibility in materials and methods of release allowed these systems to remain targets of research into the 21st century. Improved understanding of the wound environment and healing cascades has led to the development of more advanced systems which incorporate endogenous growth factors and living cells. Despite their promise, clinical efficacy of these systems has remained a challenge. Further, the regulatory pathways for approval add a layer of complexity to translate pre-clinical work into marketed products. In this review, we discuss systems currently in clinical use, pre-clinical directions and regulatory challenges for hydrogels in the treatment of diabetic chronic wounds.","PeriodicalId":87311,"journal":{"name":"Journal of pharmaceutics & drug delivery research","volume":"10 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45124445","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}

{"title":"Fabrication of Paclitaxel and 17AAG-loaded Poly-ε-Caprolactone Nanoparticles for Breast Cancer Treatment.","authors":"Y A Berko,&nbsp;A F Funmilola,&nbsp;E O Akala","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to design, fabricate and determine the cytotoxic effects of dual loaded paclitaxel and 17-AAG in stealth polymeric nanoparticles. The nanoparticles were fabricated by dispersion polymerization.</p><p><strong>Methods: </strong>Two breast cancer cell lines (MCF-7 and SKBR-3) were cultured and treated with media only, blank nanoparticles, paclitaxel (as a free drug), 17-AAG (free drug), paclitaxel + 17-AAG combination (as free drugs), and paclitaxel + 17-AAG combination loaded in poly-ε-caprolactone stealth nanoparticles. Each drug in the combination was half the concentration of the single free drug.</p><p><strong>Results: </strong>The cytotoxic effects of the paclitaxel treatment and that of the combination (free drug) were found to be similar in both SKBR3 and MCF7 cell lines. Similar cytotoxic effects were observed for the drug combination both in the drug loaded nanoparticles formulation and in free drug form for both cell lines.</p><p><strong>Conclusion: </strong>Both paclitaxel and 17-AAG were effectively loaded and released from the polymeric nanoparticles. Paclitaxel (free drug), paclitaxel-17AAG combination (free drug), and dual drug-loaded nanoparticles had similar cytotoxic effects on both cell lines. Paclitaxel and 17-AAG combination resulted in synergistic effect: paclitaxel in the combination with 17-AAG was half its original concentration and yielded similar cytotoxic effect. The dose of paclitaxel was reduced without lowering its therapeutic efficacy.</p>","PeriodicalId":87311,"journal":{"name":"Journal of pharmaceutics & drug delivery research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932184/pdf/nihms-1665322.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25445965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel Dressings for Chronic Wound Healing in Diabetes: Beyond Hydration.","authors":"Paul R Hartmeier, Ngoc B Pham, Ketki Y Velankar, Fadi Issa, Nick Giannoukakis, Wilson S Meng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chronic wounds caused by diabetes are a significant medical challenge. Complications from non-healing can result in dire consequences for patients and cost the healthcare system billions of dollars annually. Non-healing in wounds for diabetic patient's results from a combination of factors which impair clearing of injured tissue, proliferation of healthy cell populations and increase risk of infection. Wound dressings continue to form the basis for the treatment of chronic wounds. Traditionally, these focused solely on hydration of the wound site and mitigating infection risk. Hydrogel systems are ready made to meet these basic requirements due to their intrinsic hydration properties and ability to deliver active ingredients. Flexibility in materials and methods of release allowed these systems to remain targets of research into the 21st century. Improved understanding of the wound environment and healing cascades has led to the development of more advanced systems which incorporate endogenous growth factors and living cells. Despite their promise, clinical efficacy of these systems has remained a challenge. Further, the regulatory pathways for approval add a layer of complexity to translate pre-clinical work into marketed products. In this review, we discuss systems currently in clinical use, pre-clinical directions and regulatory challenges for hydrogels in the treatment of diabetic chronic wounds.</p>","PeriodicalId":87311,"journal":{"name":"Journal of pharmaceutics & drug delivery research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473423/pdf/nihms-1834059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40361462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fludarabine- (C2-methylhydroxyphosphoramide)- [anti-IGF-1R]: Synthesis and Selectively \"Targeted\"Anti-Neoplastic Cytotoxicity against Pulmonary Adenocarcinoma (A549).","authors":"Coyne Cp, L. Narayanan","doi":"10.4172/2325-9604.1000129","DOIUrl":"https://doi.org/10.4172/2325-9604.1000129","url":null,"abstract":"INTRODUCTION Many if not most conventional small molecular weight chemotherapeutics are highly potent against many forms of neoplastic disease. Unfortunately, majority of an administered dose unintentionally diffuses passively into normal tissues and healthy organ systems following intravenous administration. One strategy for both increasing potency and reducing dose-limited sequela is the selective \"targeted\" delivery of conventional chemotherapeutic agents. MATERIALS AND METHODS The fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] was synthesized by initially reacting fludarabine with a carbodiimide to form a fludarabine carbodiimide phosphate ester intermediate that was subsequently reacted with imidazole to create an amine-reactive fludarabine- (C2-phosphorylimidazolide) intermediate. Monoclonal anti-IGF-1R immunoglobulin was combined with the amine-reactive fludarabine- (C2-phosphorylimidazolide) intermediate resulting in the synthesis of covalent fludarabine-(C2-methylhydroxyphosphoramide)- [anti-IGF-1R] immunochemotherapeutic. Residual fludarabine and un-reacted reagents were removed by serial microfiltration (MWCO 10,000) and monitored by analytical-scale HP-TLC. Retained IGF-1R binding-avidity of fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] was established by cell-ELISA using pulmonary adenocarcinoma cell (A549) which over-expresses IGF-1R and EGFR. Anti-neoplastic cytotoxic potency of fludarabine-(C2-methylhydroxyphosphoramide)-[anti- IGF-1R] was determined against pulmonary adenocarcinoma (A549) using an MTT-based vitality stain methodology. RESULTS The fludarabine molar-incorporation-index for fludarabine- (C2-methylhydroxyphosphoramide)-[anti-IGF-R1] was 3.67:1 while non-covalently bound fludarabine was not detected by analytical scale HP-TLC following serial micro-filtration. Size-separation fludarabine-(C2-methylhydroxyphosphoramide)-[anti- IGF-1R] by SDS-PAGE with chemo luminescent autoradiography detected only a single 150-kDa band. Cell-ELISA of fludarabine- (C2-methylhydroxyphosphoramide)-[anti-IGF-1R] measuring total immunoglobulin bound to exterior surface membranes of pulmonary adenocarcinoma (A549) increased with elevations in immunoglobulin-equivalent concentrations of the covalent fludarabine immunochemotherapeutic. Between the fludarabine-equivalent concentrations of 10-10 M and 10-5 M both fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] and fludarabine had ex-vivo anti-neoplastic cytotoxic potency levels that increased rapidly between the fludarabine-equivalent concentrations of 10-6 M and 10-5 M where cancer cell death percentages increased from 24.4% to a maximum of 94.7% respectively. CONCLUSION The molecular design and organic chemistry reaction schemes were developed for synthesizing fludarabine-(C2- methylhydroxyphosphoramide)-[anti-IGF-1R] which possessed both properties of selective \"targeted\" delivery and anti-neoplastic cytotoxic potency equivalent to fludarabine chemot","PeriodicalId":87311,"journal":{"name":"Journal of pharmaceutics & drug delivery research","volume":"4 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70250580","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}