title: Kanamycin Sulphate Loaded PLGA-Vitamin-E-TPGS Long Circulating Nanoparticles Using Combined Coating of PEG and Water-Soluble Chitosan.
abstract: Kanamycin sulphate (KS) is aMycobacterium tuberculosisprotein synthesis inhibitor. Due to its intense hydrophilicity, KS is cleared from the body within 8 h. KS has a very short plasma half-life (2.5 h). KS is used in high concentrations to reach the therapeutic levels in plasma, which results in serious nephrotoxicity/ototoxicity. To overcome aforementioned limitations, the current study aimed to develop KS loaded PLGA-Vitamin-E-TPGS nanoparticles (KS-PLGA-TPGS NPs), to act as an efficient carrier for controlled delivery of KS. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to KS-PLGA-TPGS NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was raised for surface modification of NPs. Surface modified NPs (KS-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetics and in vivo biodistribution following intramuscular administration were investigated. NPs surface charge was close to neutral +3.61 mV and significantly affected by the WSC coating. KS-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long drew-out the blood circulation half-life with resultant reduced kidney sequestrationvis-à-visKS-PLGA-TPGS NPs. The studies, therefore, indicate the successful formulation development of KS-PEG-WSC NPs with reduced frequency of dosing of KS indicating low incidence of nephrotoxicity/ototoxicity.
authors.affiliation: Pharmaceutics Division, Faculty of Pharmacy, Al-Ameen College of Pharmacy, Bangalore, Karnataka 560027, India.
authors.forename: Sanaul
authors.initials: S
authors.lastname: Mustafa
authors.affiliation: Pharmaceutics Division, Faculty of Pharmacy, Al-Ameen College of Pharmacy, Bangalore, Karnataka 560027, India.
authors.forename: V Kusum
authors.identifier: 0000-0002-3265-8929
authors.initials: VK
authors.lastname: Devi
authors.affiliation: Pharmaceutics Division, Faculty of Pharmacy, Al-Ameen College of Pharmacy, Bangalore, Karnataka 560027, India.
authors.forename: Roopa S
authors.identifier: 0000-0003-4840-4429
authors.initials: RS
authors.lastname: Pai