Organic solvent-free low temperature method of preparation for self assembled amphiphilic poly(ϵ-caprolactone)-poly(ethylene glycol) block copolymer based nanocarriers for protein delivery.
Degradation and denaturation of labile biomolecules during preparation of micelles by organic solvent at high temperature are some of the limitations for fabrication of advanced polymer based protein delivery systems. In this paper, effectiveness of heat-chill method for preparation of micelles containing large labile biomolecules was investigated using insulin as a model protein molecule. Micelles (average size, <120 nm) were prepared using amphiphilic diblock and triblock copolymers of poly(ethylene glycol) (PEG) and poly(ϵ-caprolactone) (PCL). Micelles were prepared by heating PEG-PCL block copolymers with distilled water at 60 °C followed by sudden chilling in an ice-water bath. Effects of molecular architecture on morphology, stability and protein loading capacity of micelles were investigated. Micelles prepared using high molecular weight block copolymers exhibited good colloidal stability, encapsulation efficiency and insulin release characteristics. Insulin retained its secondary structure after micelles preparation as confirmed by CD spectroscopic study. Furthermore, in vitro cytotoxicity test suggested that the prepared micellar nanoparticles possessed biocompatibility. In a nut shell, heat-chill method of micellar nanoparticles preparation is well suited for encapsulating labile proteins and other allied biomolecules which degrade in presence of toxic organic solvents and at elevated temperatures.
Rubber Technology Centre, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.
Sanal Sebastian
SS
Payyappilly
Rubber Technology Centre, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.
Sudipta
S
Panja
Rubber Technology Centre, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.
Pijush
P
Mandal
School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.
Santanu
S
Dhara
Rubber Technology Centre, Indian Institute of Technology, Kharagpur, West Bengal 721302, India. Electronic address: santanuchat71@yahoo.om.
Santanu
S
Chattopadhyay
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004339:Drug Compounding; D016503:Drug Delivery Systems; D007328:Insulin / Q000008:administration & dosage; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D013816:Thermodynamics
D004337:Drug Carriers; D007328:Insulin; D008823:Micelles; D011091:Polyesters; D011506:Proteins; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols
Amphiphilic nanoparticles; Biodegradable; Block copolymers; Gene delivery; Heat–chill; Insulin; Micellar nanoparticle; Organic solvent free; PEG-PCL; Polycaprolactone; Polyethylene glycol; Polymer micelle; Protein degradation; Protein delivery; Protein denaturation