Abstract
This investigation focused on the design of an injectable nano-enabled thermogel (nano-thermogel) system to attain controlled delivery of p11 anti-angiogenic peptide for proposed effective prevention of neovascularisation and to overcome the drawbacks of the existing treatment approaches for ocular disorders characterised by angiogenesis, which employ multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) antibodies. Synthesis of a polyethylene glycol-polycaprolactone-polyethylene glycol (PEG-PCL-PEG) triblock co-polymer was undertaken, followed by characterisation employing Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) to ascertain the chemical stability and integrity of the co-polymer instituted for nano-thermogel formulation. The p11 anti-angiogenic peptide underwent encapsulation within poly(lactic-co-glycolic acid) (PLGA) nanoparticles via a double emulsion solvent evaporation method and was incorporated into the thermogel following characterisation by scanning electron microscopy (SEM), zeta size and zeta-potential analysis. The tube inversion approach and rheological analysis were employed to ascertain the thermo-sensitive sol-gel conversion of the nano-thermogel system. Chromatographic assessment of the in vitro release of the peptide was performed, with stability confirmation via Tris-Tricine PAGE (Polyacrylamide Gel Electrophoresis). In vitro biocompatibility of the nano-thermogel system was investigated employing a retinal cell line (ARP-19). A nanoparticle size range of 100–200 nm and peptide loading efficiency of 67% was achieved. Sol-gel conversion of the nano-thermogel was observed between 32–45 °C. Release of the peptide in vitro was sustained, with maintenance of stability, for 60 days. Biocompatibility assessment highlighted 97–99% cell viability with non-haemolytic ability, which supports the potential applicability of the nano-thermogel system for extended delivery of peptide for ocular disorder treatment.
Highlights
Retinopathy of prematurity (RP), age-related macular degeneration (AMD) and diabetic retinopathy (DR) are angiogenesis-related ocular diseases, which are prevalent from youth to old age and are principally attributed to the occurrence of irreversible blindness globally [1,2,3]
It was observed that as the agitation time of the second emulsion increased, the particle size decreased from 416 nm to 110 nm. This reduction in particle size is a common observation, with the increasing shear rate from the increased stirring speed reducing the droplet size of the emulsion and the nanoparticles formed, as observed for example by Geng et al [31] for their poly(lactic-co-glycolic acid) (PLGA)
This study focused on an anti-angiogenic hexapeptide, having the PDZ binding motif (Ser-Asp-Val) possessing high affinity to alpha v beta 3 integrin molecules whose anti-angiogenic effect has been already studied and established using human endothelial cells
Summary
Retinopathy of prematurity (RP), age-related macular degeneration (AMD) and diabetic retinopathy (DR) are angiogenesis-related ocular diseases, which are prevalent from youth to old age and are principally attributed to the occurrence of irreversible blindness globally [1,2,3]. Even though these diseases affect all age groups, the pathology of these diseases are similar and include abnormal neovascularisation. Growth of new blood vessels from the retina of DR and RP patients leads to bleeding inside the vitreous and ends in fibrosis and visual loss [4].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
