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• W2256518062 endingPage "2922" @default.
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• W2256518062 abstract "The purpose of this investigation is to design and synthesize novel pentablock (PB) copolymer (PB-1: PCL-PLA-PEG-PLA-PCL) based nanoformulations suspended in a thermosensitive gelling copolymer (PB-2: mPEG-PCL-PLA-PCL-PEGm) termed as composite nanoformulation. The composite nanoformulation was prepared to provide a sustained delivery of macromolecules over a longer duration with negligible burst release effect. The delivery system was designed to be utilized for the treatment of posterior segment ocular diseases such as age-related (wet) macular degeneration, diabetic retinopathy, and diabetic macular edema. The novel PB copolymers were characterized for their functional groups by Fourier transform infrared spectroscopy, molecular weight and purity by (1)H NMR spectroscopy, and gel permeation chromatography. X-ray diffraction analysis was used to determine the crystallinity of copolymers. The size distribution of PB-1 nanoparticles (NPs) prepared using emulsification-solvent evaporation method was found to be ∼150 nm analyzed by nanoparticle tracking analysis. The % encapsulation efficiency and % drug loading were found to be 66.64% w/w ± 1.75 and 18.17% w/w ± 0.39, respectively, (n = 3). Different weight percentages (15 and 20 wt %) of the PB-2 copolymer have been utilized for in vitro release studies of IgG-Fab from composite nanoformulation. A negligible burst release with continuous near zero-order release has been observed from the composite nanoformulation analyzed up to 80 days. In vitro cell viability and biocompatibility studies performed on ocular (human corneal epithelial and retinal pigment epithelium) and mouse macrophage (RAW 264.7) cell lines showed that the synthesized PB copolymer based composite nanoformulations were safe for clinical applications. On the basis of the results observed, it is concluded that PB copolymer based composite nanoformulations can serve as a platform for ocular delivery of therapeutic proteins. In addition, the composite nanoformulation may provide minimal side effects associated with frequent intravitreal injections." @default.
• W2256518062 created "2016-06-24" @default.
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• W2256518062 date "2016-02-26" @default.
• W2256518062 modified "2023-10-11" @default.
• W2256518062 title "Composite Nanoformulation Therapeutics for Long-Term Ocular Delivery of Macromolecules" @default.
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• W2256518062 doi "https://doi.org/10.1021/acs.molpharmaceut.5b00828" @default.
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