title: Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: In Vitro and in Vivo Evaluations.
abstract: It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can enhance the drug loading of tenofovir, a model low molecular weight and highly water-soluble drug molecule, and improve its mucoadhesivity and in vivo safety. To test this hypothesis, poly(ethylene oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analyzed using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, fluorescence imaging and periodic acid colorimetric method, respectively. In vivo safety studies are performed in C57BL/6 mice followed by H&E and immunohistochemical (CD45) staining analysis of genital tract. The mean diameters of PEO, PEO/TCS, and PEO/TCS-PLA NFs are 118.56, 9.95, and 99.53 nm, respectively. The NFs exhibit smooth surface. The drug loading (13%-25%, w/w) increased by 10-fold compared to a nanoparticle formulation due to the application of the electrospinning technique. The NFs are noncytotoxic at the concentration of 1 mg/mL. The PEO/TCS-PLA core/shell NFs mostly exhibit a release kinetic following Weibull model (r2= 0.9914), indicating the drug release from a matrix system. The core/shell NFs are 40-60-fold more bioadhesive than the pure PEO based NFs. The NFs are nontoxic and noninflammatory in vivo after daily treatment for up to 7 days. Owing to their enhanced drug loading and preliminary safety profile, the TCS core/shell NFs are promising candidates for the topical delivery of HIV/AIDS microbicides such as tenofovir.
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics Division of Pharmaceutical Sciences, University of Missouri-Kansas City , Kansas City, Missouri 64108, United States.
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, United States.
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, United States.
authors.forename: Miezan J
authors.initials: MJ
authors.lastname: Ezoulin
authors.affiliation: Department of Chemistry, University of Missouri-Kansas City , Kansas City, Missouri 64110, United States.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Missouri-Kansas City , Kansas City, Missouri 64110, United States.
authors.forename: Sudhaunshu S
authors.initials: SS
authors.lastname: Purohit
authors.affiliation: School of Medicine, University of Missouri-Kansas City , Kansas City, Missouri 64108, United States.
authors.forename: Agostino
authors.initials: A
authors.lastname: Molteni
authors.affiliation: School of Medicine, University of Missouri-Kansas City , Kansas City, Missouri 64108, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dim
authors.affiliation: Department of Chemistry, University of Missouri-Kansas City , Kansas City, Missouri 64110, United States.
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, United States.
authors.forename: Bi-Botti C
authors.initials: BC
authors.lastname: Youan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D057139:Nanofibers / Q000008:administration & dosage / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D000068698:Tenofovir / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018894:Reverse Transcriptase Inhibitors; D013438:Sulfhydryl Compounds; D048271:Chitosan; D000068698:Tenofovir
keywords: coaxial electrospinning; drug loading; mucoadhesion; nanofiber; water-soluble drug