Biodegradable and biocompatible thermosensitive polymer based injectable implant for controlled release of protein.
This study was aimed at developing a suitable controlled release system for proteins by modifying the structure of thermosensitive copolymer monomethoxy poly(ethylene-glycol)-co-poly(D,L-lactide-co-glycolide)-co-monomethoxy poly(ethylene-glycol) (mPEG-PLGA-mPEG). Eleven mPEG-PLGA-mPEG copolymers were synthesized and characterized by (1)H NMR and gel permeation chromatography (GPC). Thermosensitivity of the copolymers was tested using the tube inversion method. Four of the eleven synthesized copolymers were dissolved in water as injectable solutions at room temperature which turned into gels abruptly at body temperature (37 degrees C), indicating the potential use as in vivo drug delivery system. Lysozyme was used as a model protein to study in vitro release characteristics of the copolymer based delivery system. The copolymer based formulations released lysozyme (quantified by micro-BCA protein assay) over 10-30 days, depending on copolymer structure. The released lysozyme was confirmed to conserve its structural stability by differential scanning calorimetry (DSC) and circular dichroism (CD), and biological activity by specific enzyme activity assay. Furthermore, the copolymer based formulations showed excellent biocompatibility as tested by MTT assay and in vivo histological evaluation. Therefore, the copolymers controlled the in vitro release of lysozyme while conserving protein stability and biological activity, indicating that it is an appropriate delivery system for long term controlled release of proteins.
Tang
Yu
Y
Department of Pharmaceutics, North Dakota State University, Fargo, ND 58105, USA.
Singh
Jagdish
J
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002942:Circular Dichroism; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D004343:Drug Implants; D004355:Drug Stability; D005260:Female; D005782:Gels; D006801:Humans; D009113:Muramidase / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry*; D011098:Polyglactin 910 / Q000009:adverse effects / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D013997:Time Factors
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D005782:Gels; C520330:polyethylene glycol-poly(lactic-co-glycolic acid)-polyethylene glycol; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D009113:Muramidase