title: Polymeric emulsion and crosslink-mediated synthesis of super-stable nanoparticles as sustained-release anti-tuberculosis drug carriers.
abstract: This study focused on evaluating four emulsion-based processing strategies for polymeric nanoparticle synthesis to explicate the mechanisms of nanoparticle formation and the influence on achieving sustained-release of two anti-tuberculosis drugs, isoniazid and rifampicin. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were formulated with and without sorbitan mono-oleate as a stabilizer using emulsion-solvent-surfactant-evaporation (ESSE) and emulsion-solvent-evaporation (ESE) approaches. An alginate solution gelled by ionic crosslinking with calcium chloride was employed to prepare alginate hydrogel nanoparticles via reverse-emulsion-cationic-gelification (RECG) and reverse-emulsion-surfactant-cationic-gelification (RESCG) approaches. In vitro drug release analysis was performed. The size, zeta potential and morphology of the nanoparticles were analyzed. Molecular mechanics energy relationships (MMER) were employed to explore the spatial disposition of alginate and PLGA with respect to the emulsifying profile of sorbitan monooleate and to corroborate the experimental findings. Results revealed that particle size of the PLGA nanoparticles was influenced by the stabilizer concentration. Nanoparticles synthesized by the ESSE approach had smaller sizes of 240±8.7 nm and 195.5±5.4 nm for rifampicin- and isoniazid-loaded nanoparticles, respectively. This was a substantial size reduction from nanoparticles generated by the ESE approach (>1000 nm). The RESCG approach produced stable and higher nanoparticle yields with desirable size (277±1.0 nm; 289±1.2 nm), a low polydispersity index (27.1±0.3 mV; 28.5±0.5 mV) and drug entrapment efficiency of 73% and 75% for isoniazid and rifampicin, respectively. Drug release from the ESSE and RESCG synthesized nanoparticles displayed desirable release of the two anti-TB drugs with sustained zero-order kinetics over a period of 8h. MMER supported the mechanisms of nanoparticle formation with a sphericalized interlaced network configuration.
authors.affiliation: University of the Witwatersrand, Department of Pharmacy and Pharmacology, Johannesburg, South Africa.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Riaz A
authors.initials: RA
authors.lastname: Khan
authors.forename: Caragh S
authors.initials: CS
authors.lastname: Murphy
authors.forename: Debbie-Leigh
authors.initials: DL
authors.lastname: Jarvis
mesh_terms: D000464:Alginates / Q000737:chemistry; D002122:Calcium Chloride / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000378:metabolism*; D004339:Drug Compounding / Q000379:methods*; D004655:Emulsions / Q000737:chemistry / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006601:Hexoses / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007538:Isoniazid / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D055601:Organic Chemistry Phenomena; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012293:Rifampin / Q000378:metabolism; D013057:Spectrum Analysis; D013816:Thermodynamics; D014376:Tuberculosis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D006601:Hexoses; D006603:Hexuronic Acids; D020100:Hydrogels; C018665:sorbitan monooleate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid; D002122:Calcium Chloride; D007538:Isoniazid; D012293:Rifampin