title: Comparative study of kanamycin sulphate microparticles and nanoparticles for intramuscular administration: preparation in vitro release and preliminary in vivo evaluation.
abstract: Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. KS is polycationic, a property responsible for KS poor oral absorption half-life (2.5 h) and rapid renal clearance, which results in serious nephrotoxicity/ototoxicity. The current study aimed to develop KS-loaded PLGA vitamin-E-TPGS microparticles (MPs) and nanoparticles (NPs) to reduce the dosing frequency and dose-related adverse effect. In vitro release was sustained up to 10 days for KS PLGA-TPGS MPs and 13 days for KS PLGA-TPGS NPs in phosphate-buffered saline (PBS) pH 7.4. The in vivo pharmacokinetic test in Wistar rats showed that the AUC0-∞of KS PLGA-TPGS NPs (280.58 μg/mL*min) was about 1.62-fold higher than that of KS PLGA-TPGS MPs (172.30 μg/mL*min). Further, in vivo protein-binding assay ascribed 1.20-fold increase in the uptake of KS PLGA-TPGS NPs through the alveolar macrophage (AM). The studies, therefore, could provide another useful tool for successful development of KS MPs and NPs.
authors.affiliation: a Pharmaceutics Division, Faculty of Pharmacy , Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
authors.forename: Sanaul
authors.initials: S
authors.lastname: Mustafa
authors.affiliation: a Pharmaceutics Division, Faculty of Pharmacy , Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
authors.forename: V Kusum
authors.initials: VK
authors.lastname: Devi
authors.affiliation: a Pharmaceutics Division, Faculty of Pharmacy , Al-Ameen College of Pharmacy , Bangalore , Karnataka , India.
authors.forename: Roopa S
authors.initials: RS
authors.lastname: Pai
mesh_terms: D000818:Animals; D007273:Injections, Intramuscular; D007612:Kanamycin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007612:Kanamycin
keywords: Microparticles; PLGA; in vivo distribution; nanoparticles; pharmacokinetic