Injectable Supramolecular Hydrogel from Insulin-Loaded Triblock PCL-PEG-PCL Copolymer and γ-Cyclodextrin with Sustained-Release Property

Abstract

Abstract. Supramolecular hydrogels formed by cyclodextrins and polymers have been widely investigated as a biocompatible, biodegradable and controllable drug delivery system. In this study, a supramolecular hydrogel based on biodegradable poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) triblock copolymers and γ-cyclodextrin (γ-CD) was prepared through inclusion complexation as an injectable, sustained-release vehicle for insulin. The triblock copolymer PCL-PEG-PCL was synthesised by the ring-opening polymerisation method, using microwave irradiation. The polymerisation reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The supramolecular hydrogel was prepared in aqueous solution by blending an aqueous γ-CD solution with an aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. In vitro insulin release through the hydrogel system was studied. The relative surface hydrophobicity of standard and released insulin from the SMGel was estimated using 8-anilino-1-naphthalene sulfonic acid (ANS). Results of 1 HNMR and gel permeation chromatography revealed that microwave irradiation is a simple and reliable method for synthesis of PCL-PEG-PCL copolymer. Gelation occurred within a minute. The supramolecular hydrogel obtained by mixing 10.54% (w/v) γ-CD and 2.5% (w/v) copolymer had an excellent syringeability. Insulin was released up to 80% over a period of 20 days. Insulin kept its initial folding after formulating and releasing from SMGel. A supramolecular hydrogel based on complexation of triblock PCL-PEG-PCL copolymer with γ-cyclodextrin is a suitable system for providing sustained release of therapeutic proteins, with desirable flow behaviour.

Biocompatible Polymers Combined with Cyclodextrins: Fascinating Materials for Drug Delivery Applications

“…The PCL/PEG copolymers and CD-based supramolecular hydrogels (SMGels) with their reversible sol-gel transition properties were widely explored as injectable biomaterials capable of establishing versatile drug delivery systems [70,86,118]. The SMGel based on α-CD [87,119], β-CD [64], or γ-CD [86] and PCL/PEG copolymers of various microstructure were developed and investigated due to their controlled drug release and site-specific drug delivery triggered by various stimuli. The advantage of SMGel is the dynamic nature of their structure that can be easily broken by shear forces because it is composed of weak noncovalent interaction.…”

Injectable and thermosensitive TGF-β1-loaded PCEC hydrogel system for in vivo cartilage repair

“…PCEC hydrogel has been employed to delivery various drugs such as hydrophobic, hydrophilic and protein ones owing to its unique amphiphilic micelle-like structure 40 – 43 . Additionally, researches have proved the protection and bioactivity preservation of PCEC hydrogel analogies to proteins like insulin 43 . Our release results may still seem fast and we ascribed this to the insufficiency of hydrogel protection.…”

Immunoadjuvant potential of cross-linked dextran microspheres mixed with chitosan nanospheres encapsulated with tetanus toxoid

“…The structural stability of released TT from nanospheres was detected by sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS–PAGE) and compared with native TT as perviosly described (Khodaverdi et al. 2015 ). Antigen samples were diluted with Tris-buffer (pH 6.8) with 2% SDS and electrophoresis of samples was performed using a Bio-RadMiNi-Protein II electrophoresis system at a constant voltage of 200 V in a Tris/glycine/SDS buffer.…”