An injectable biodegradable hydrogel was prepared for temperature-responsive pulsatile release of insulin. Triblock copolymer of poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) was prepared by ring opening bulk copolymerization and characterized using FT-IR, (1) HNMR, and gel permeation chromatography. Aqueous solution of PECE formed an injectable hydrogel, which was solution at room temperature and transformed into gel at 37°C. The temperature-responsive sol-gel transition and crystallinity of PECE hydrogel was studied and compared with pluronic, a well-studied nonbiodegradable injectable hydrogel. In vitro release study revealed that insulin release profile of PECE was similar to pluronic, and its viscosity was 1/30(th) of pluronic sol at 10,000 s(-1) shear rate. Release behavior of insulin from PECE hydrogels followed Fickian diffusion of first order. Insulin retained its secondary structure after release as confirmed by circular dichroism spectrum. A threefold increase in Fickian diffusion coefficient was evidenced when temperature was increased from 34 to 40°C because of crystalline melting of PCL part of PECE. Pulsatile release of insulin showed a correlation coefficient of 0.90 with the change of temperature.
A new method is developed for preparation of amphiphilic block copolymer micellar nanoparticles and investigated as a delivery system for celecoxib, a hydrophobic model drug. Biodegradable block copolymers of poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) were synthesized by ring opening copolymerization and characterized thoroughly using FTIR, (1)H NMR and GPC. The block copolymer was dispersed in distilled water at 60 °C and then it was chilled in an ice bath for the preparation of the micellar nanoparticles. Polymers self-assembled to form micellar nanoparticles (<50 nm) owing to their amphiphilic nature. The prepared micellar nanoparticles were analyzed using HR-TEM, DLS and DSC. The cytotoxicity of the polymer micellar nanoparticles was investigated against HaCaT cell lines. The study of celecoxib release from the micellar nanoparticles was carried out to assess their suitability as a drug delivery vehicle. Addition of the drug to the system at low temperature is an added advantage of this method compared to the other temperature assisted nanoparticle preparation techniques. In a nutshell, polymer micellar nanoparticles prepared using the heat-chill method are believed to be promising for the controlled drug release system of labile drugs, which degrade in toxic organic solvents and at higher temperatures.
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