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VIBHUTI AGRAHARI, Sulabh P Patel, Ashim K Mitra; Novel Pentablock Copolymer Based Nanoformulations for Sustained Ocular Delivery of Protein Therapeutics. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4628.
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In this study, protein encapsulated sustained release nanoformulation has been synthesized and evaluated using novel tailor made pentablock (PB) copolymer for the treatment of posterior segment eye diseases. The effect of block arrangements of PB copolymers on encapsulation efficiency (EE), drug loading (DL) and release profile was studied.
Hydrophobic and hydrophilic PB copolymers with different block ratios of PEG/PCL/PLA were synthesized by ring-opening copolymerization method and characterized by 1H-NMR spectroscopy, gel permeation chromatography (GPC) and X-ray diffraction (XRD) analysis. The hydrophobic PB copolymer (PCL-PLA-PEG-PLA-PCL) was utilized to prepare nanoparticles (NPs) while hydrophilic polymer (PEG-PCL-PLA-PCL-PEG) was used for the preparation of thermosensitive gel. The NP preparation method was optimized to improve entrapment efficiency (EE) and drug loading (DL) of protein macromolecules. Cytotoxicity (MTS and LDH) assays were performed on HCEC and ARPE-19 cell lines to study the in vitro cell viability. In addition, biocompatibility study of the PB copolymers was evaluated on macrophage (RAW 264.7) cell line.
The molecular weight and purity of the PB copolymers were confirmed by 1H-NMR and GPC. XRD study revealed that the arrangement of polymeric blocks controls the crystalline or amorphous nature of PB copolymer. The solvent evaporation (W1/0/W2) NP preparation method was successfully optimized and a remarkably improved EE (~ 46% to 76%) and DL (~15% to 18%) have been observed. Results of in vitro studies depicted zero ordered drug release of NPs for a significantly longer period of time (~ 90 days) without showing any burst release effect. PB copolymers demonstrated higher cell viability on HCEC and ARPE-19 cell lines. The in vitro biocompatibility assay exhibited negligible release of cytokines suggesting the biocompatible nature of PB copolymers.
Novel PB copolymer based nanoformulations were successfully prepared and optimized. Results showed that the PB copolymers can be used as a platform for the treatment of posterior segment ocular diseases.
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