{"title":"Poloxamer 188 stabilized poly (ε-caprolactone) microspheres of voriconazole for targeting pulmonary aspergillosis.","authors":"Aayush Singh, Atul Mourya, Hoshiyar Singh, Gopal Bajad, Bhavana Bojja, Shristi Arya, Shalini Devi, Santosh Kumar Guru, Jitender Madan","doi":"10.1080/20415990.2024.2441647","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>Voriconazole (VRZ) is highly effective in treating invasive pulmonary aspergillosis (IPA), in addition to hepatotoxicity. Therefore, the current study focuses on the development and characterization of voriconazole-loaded microspheres (VRZ@PCL MSPs) to augment pulmonary localization and antifungal efficacy.</p><p><strong>Methods: </strong>VRZ@PCL MSPs were fabricated by using the o/w emulsion method. The optimized F3VRZ@PCL MSPs were subjected to physicochemical characterization, in vitro release, hemocompatibility, antifungal efficacy as well as pharmacokinetic and biodistribution evaluation.</p><p><strong>Results: </strong>The optimized F3VRZ@MSPs exhibited a particle size (10.90 ± 2.61 µm), entrapment efficiency (19.35 ± 2.47%), drug loading (3.22 ± 0.41%) with sustained release behavior up to 24 h and hemocompatibility upto 50 µg/mL. Results of antifungal testing indicated the superior antifungal potential of F3VRZ@PCL MSPs as compared to free VRZ and nystatin. In vivo pharmacokinetic evaluation in Sprague-Dawley rats displayed 12.5-fold and 4.5-fold increments, respectively, in t<sub>1/2</sub> and AUC<sub>0-t</sub> of F3VRZ@PCL MSPs as compared to free VRZ. Moreover, F3VRZ@PCL MSPs displayed relatively higher lung targeting with a drug targeting index (DTI) of 0.213 as compared to DTI of 0.037 of free VRZ.</p><p><strong>Conclusion: </strong>In conclusion, F3VRZ@PCL MSPs offer a promising approach for sustained and targeted delivery of VRZ and hold the potential to offer high therapeutic efficacy in the treatment of IPA.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"1-12"},"PeriodicalIF":3.0000,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic delivery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/20415990.2024.2441647","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: Voriconazole (VRZ) is highly effective in treating invasive pulmonary aspergillosis (IPA), in addition to hepatotoxicity. Therefore, the current study focuses on the development and characterization of voriconazole-loaded microspheres (VRZ@PCL MSPs) to augment pulmonary localization and antifungal efficacy.
Methods: VRZ@PCL MSPs were fabricated by using the o/w emulsion method. The optimized F3VRZ@PCL MSPs were subjected to physicochemical characterization, in vitro release, hemocompatibility, antifungal efficacy as well as pharmacokinetic and biodistribution evaluation.
Results: The optimized F3VRZ@MSPs exhibited a particle size (10.90 ± 2.61 µm), entrapment efficiency (19.35 ± 2.47%), drug loading (3.22 ± 0.41%) with sustained release behavior up to 24 h and hemocompatibility upto 50 µg/mL. Results of antifungal testing indicated the superior antifungal potential of F3VRZ@PCL MSPs as compared to free VRZ and nystatin. In vivo pharmacokinetic evaluation in Sprague-Dawley rats displayed 12.5-fold and 4.5-fold increments, respectively, in t1/2 and AUC0-t of F3VRZ@PCL MSPs as compared to free VRZ. Moreover, F3VRZ@PCL MSPs displayed relatively higher lung targeting with a drug targeting index (DTI) of 0.213 as compared to DTI of 0.037 of free VRZ.
Conclusion: In conclusion, F3VRZ@PCL MSPs offer a promising approach for sustained and targeted delivery of VRZ and hold the potential to offer high therapeutic efficacy in the treatment of IPA.
期刊介绍：
Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.
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