Poly lactic acid based injectable delivery systems for controlled release of a model protein, lysozyme.
The objective of this study was to evaluate the critical formulation parameters (i.e., polymer concentration, polymer molecular weight, and solvent nature) affecting the controlled delivery of a model protein, lysozyme, from injectable polymeric implants. The conformational stability and biological activity of the released lysozyme were also investigated. Three formulations containing 10%, 20%, and 30% (w/v) poly lactic acid (PLA) in triacetin were investigated. It was found that increasing polymer concentration in the formulations led to a lower burst effect and a slower release rate. Formulation with a high molecular weight polymer showed a greater burst effect as compared to those containing low molecular weight. Conformational stability and biological activity of released samples were studied by differential scanning calorimeter and enzyme activity assay, respectively. The released samples had significantly (P < 0.05) greater conformational stability and biological activity in comparison to the control (lysozyme in buffer solution kept at same conditions). Increasing polymer concentration increased both the conformational stability and the biological activity of released lysozyme. In conclusion, phase sensitive polymer-based delivery systems were able to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over an extended period.
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
Khaled
K
Al-Tahami
Amanda
A
Meyer
Jagdish
J
Singh
D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D003627:Data Interpretation, Statistical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry*; D016982:Micrococcus luteus / Q000187:drug effects; D008968:Molecular Conformation; D008970:Molecular Weight; D009113:Muramidase / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D019999:Pharmaceutical Solutions; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*
D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D019999:Pharmaceutical Solutions; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D009113:Muramidase