title: Controlling chitosan-based encapsulation for protein and vaccine delivery.
abstract: Chitosan-based nano/microencapsulation is under increasing investigation for the delivery of drugs, biologics and vaccines. Despite widespread interest, the literature lacks a defined methodology to control chitosan particle size and drug/protein release kinetics. In this study, the effects of precipitation-coacervation formulation parameters on chitosan particle size, protein encapsulation efficiency and protein release were investigated. Chitosan particle sizes, which ranged from 300 nm to 3 μm, were influenced by chitosan concentration, chitosan molecular weight and addition rate of precipitant salt. The composition of precipitant salt played a significant role in particle formation with upper Hofmeister series salts containing strongly hydrated anions yielding particles with a low polydispersity index (PDI) while weaker anions resulted in aggregated particles with high PDIs. Sonication power had minimal effect on mean particle size, however, it significantly reduced polydispersity. Protein loading efficiencies in chitosan nano/microparticles, which ranged from 14.3% to 99.2%, were inversely related to the hydration strength of precipitant salts, protein molecular weight and directly related to the concentration and molecular weight of chitosan. Protein release rates increased with particle size and were generally inversely related to protein molecular weight. This study demonstrates that chitosan nano/microparticles with high protein loading efficiencies can be engineered with well-defined sizes and controllable release kinetics through manipulation of specific formulation parameters.
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, USA.
authors.forename: Bhanu Prasanth
authors.initials: BP
authors.lastname: Koppolu
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, USA.
authors.forename: Sean G
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, USA.
authors.forename: Sruthi
authors.initials: S
authors.lastname: Ravindranathan
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, USA.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Jayanthi
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, USA.
authors.forename: Thallapuranam K
authors.initials: TK
authors.lastname: Suresh Kumar
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, USA. Electronic address: zaharoff@uark.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Zaharoff
mesh_terms: D002151:Calorimetry; D011232:Chemical Precipitation; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D055767:Immobilized Proteins / Q000737:chemistry*; D008970:Molecular Weight; D009994:Osmolar Concentration; D010316:Particle Size; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry; D012996:Solutions; D013010:Sonication; D013431:Sulfates / Q000737:chemistry; D013816:Thermodynamics; D014612:Vaccines / Q000008:administration & dosage*; D014867:Water / Q000737:chemistry
chemical_list: D055767:Immobilized Proteins; D012996:Solutions; D013431:Sulfates; D014612:Vaccines; C039217:fluorescein isothiocyanate bovine serum albumin; D014867:Water; C012036:sodium sulfate; D012710:Serum Albumin, Bovine; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate
keywords: Chitosan particles; Microencapsulation; Nanoencapsulation; Precipitation–coacervation; Protein encapsulation; Vaccine delivery