Insulin loaded PLGA microspheres: effect of zinc salts on encapsulation, release, and stability.
The purpose of this study was to investigate the effect of three zinc salts (i.e., zinc oxide, zinc carbonate, and zinc acetate) on insulin encapsulation efficiency (EE), stability, and in vitro release kinetics from poly(lactic-co-glycolic acid) (PLGA) microspheres. Microspheres were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation technique and characterized. Integrity of the encapsulated insulin and stability of the released insulin was assessed using a wide range of comprehensive analytical techniques. The EE of the formulation prepared without the addition of a zinc salt was 69%, the secondary structure of the encapsulated insulin in this formulation was found to be altered. Further, desamido insulin and aggregates were observed during in vitro release. When insulin was encapsulated with a zinc salt, EE increased significantly, secondary structure was unaltered, and no degradation or aggregation products were found. Initial burst release and release kinetics were markedly changed with the addition of zinc salts. More than 87% of the encapsulated insulin was released over a 2-week period with the addition of a zinc salt. In conclusion, zinc salts can be useful to increase the EE and stability of insulin in PLGA microspheres prepared by w/o/w technique.
Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo 58105, USA.
Chandrasekar
C
Manoharan
Jagdish
J
Singh
D002254:Carbonates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D009821:Oils / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry; D019345:Zinc Acetate / Q000737:chemistry; D017967:Zinc Compounds / Q000737:chemistry*; D015034:Zinc Oxide / Q000737:chemistry
D002254:Carbonates; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D009821:Oils; D011994:Recombinant Proteins; D017967:Zinc Compounds; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C036650:zinc carbonate; D019345:Zinc Acetate; D015034:Zinc Oxide