Thermoresponsive gelatin/monomethoxy poly(ethylene glycol)-poly(D,L-lactide) hydrogels: formulation, characterization, and antibacterial drug delivery.
OBJECTIVE
The primary objective of this study was to prepare novel thermoresponsive binary component hydrogels composed of gelatin and monomethoxy poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PDLLA) diblock copolymer and to obtain optimal formulations capable of forming gels upon a narrow temperature range between body temperature and room temperature.


METHODS
MPEG-PDLLA diblock copolymers with a lower critical solution temperature (LCST) feature were synthesized by using a ring-opening polymerization method. The starting weight ratio of MPEG/DLLA was varied to obtain a series of copolymers with a wide range of molecular weight and hydrophilicity. The copolymers were characterized by 1H nuclear magnetic resonance (1H NMR) and thermogravimetric analysis. MPEG (2K)-PDLLA (1:4) was chosen to construct hydrogels with gelatin. To obtain optimal thermoresponsive formulation, various hydrogels were formulated and quantified in terms of sol-gel phase transition kinetics and rheological properties. Selected hydrogels were studied as drug carrier for gentamicin sulfate.


RESULTS
Gelatin/MPEG-PDLLA hydrogels underwent gelation in less than 15 min when 30 wt.% MPEG (2K)-PDLLA (1:4) was mixed with 10, 50, or 100 mg/mL gelatin. Hydrogels showed rapid gelation when 100 mg/mL gelatin was mixed with 15, 20, or 25 wt.% MPEG-PDLLA as temperature fell from 37 degrees C to room temperature. The viscosity of hydrogels depended on the frequency applied in the rheological tests, the environment temperature, and the concentration of both polymer components. The time needed for 50% gentamicin sulfate release was 5 days or longer at room temperature, and the release lasted up to 40 days. 1H NMR confirmed that MPEG-PDLLA hydrolyzed under in vitro situations.


CONCLUSIONS
The incorporation of a second polymer component MPEG-PDLLA into the gelatin hydrogel could modify the thermal characteristic of gelatin and the resulting binary component hydrogels obtained different thermal characteristics from the individual polymer components. Formulation of gelatin/MPEG-PDLLA hydrogels could be varied for obtaining such gels that can undergo gelation promptly upon a narrow temperature change.
Yang
Hu
H
School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Kao
Weiyuan John
WJ
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D005780:Gelatin / Q000737:chemistry*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008970:Molecular Weight; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
D000900:Anti-Bacterial Agents; D020100:Hydrogels; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D005780:Gelatin