title: Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.
abstract: It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state31P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively. The cytotoxicity and preclinical safety of MPs are assessed on human vaginal (VK2/E6E7) and endocervical (End1/E6E7) epithelial cell lines and in female C57BL/6 mice, respectively. The results show that the MPs are successfully formulated with an average diameter ranging from 2 to 3 μm with a drug loading of 7-12% w/w. The drug release profile of these MPs primarily follows the Baker-Lonsdale and Korsmeyer-Peppas models. The MPs exhibit high mucoadhesion (20-50 folds) compared to native AGMPs. The multilayer MPs are noncytotoxic. Histological and immunochemical analysis of the mice genital tract shows neither signs of damage nor inflammatory cell infiltrate. These data highlight the potential use of TCS-coated AG-based multilayer MPs templates for the topical vaginal delivery of anti-HIV/AIDS microbicides.
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA.
authors.forename: Jianing
authors.initials: J
authors.lastname: Meng
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Agrahari
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA.
authors.forename: Miezan J
authors.initials: MJ
authors.lastname: Ezoulin
authors.affiliation: Department of Chemistry, University of Missouri-Kansas City, Kansas City, Missouri, 64110, USA.
authors.forename: Sudhaunshu S
authors.initials: SS
authors.lastname: Purohit
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA.
authors.forename: Agostino
authors.initials: A
authors.lastname: Molteni
authors.affiliation: School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dim
authors.affiliation: Department of Chemistry, University of Missouri-Kansas City, Kansas City, Missouri, 64110, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Oyler
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA. youanb@umkc.edu.
authors.forename: Bi-Botti C
authors.initials: BC
authors.lastname: Youan
mesh_terms: D000282:Administration, Intravaginal; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002460:Cell Line; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D008810:Mice, Inbred C57BL; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D000068698:Tenofovir / Q000008:administration & dosage*; D018675:Toxicity Tests
chemical_list: D000464:Alginates; D019380:Anti-HIV Agents; D006603:Hexuronic Acids; D013438:Sulfhydryl Compounds; D020723:Glucuronic Acid; D048271:Chitosan; D000068698:Tenofovir
keywords: microbicide; microparticles; mucoadhesive; spray drying; thiolated chitosan