Sustained intravitreal delivery of connexin43 mimetic peptide by poly(d,l-lactide-co-glycolide) acid micro- and nanoparticles – Closing the gap in retinal ischaemia

Connexin channel and its role in diabetic retinopathy

“…The in vitro cell study from the same paper confirms that the endothelial cell death is mediated by opening of Cx43 hemichannels. Due to a potential challenge of delivering natural peptides due to poor stability, a follow-up study is reported by using Cx43 mimetic peptides encapsulated into slow release nano- and microparticles (Chen et al, 2015b). The treatment with the above nanoparticles results in retinal ganglion cell rescue, while microparticles exhibit a delayed effect on retinal ganglion cell preservation albeit the initial inflammatory response due to the size of microparticles.…”

“…In another study, Peptide5 is similarly delivered via intraperitoneal injection in albino rat model and this treatment reduces neuronal damages likely by reducing choroid inflammation caused by light damage (Guo et al, 2016). The approaches for new peptide drug formulation and delivery are reported in two papers; in the first paper, Cx43 mimetic peptides are encapsulated into slow-release poly(lactic-co-glycolic) acid nanoparticles and microparticles and a triphasic release is shown in vitro with an initial burst release and following a slow release (Chen et al, 2015b). The sustained intravitreal delivery with these Cx43 mimetic peptide-containing nano- and microparticles increases retinal ganglion cell viability.…”

Translating connexin biology into therapeutics

“…In the case of antisense, the upregulation of new connexin hemichannels following injury is prevented, although this approach also leads to a transient reduction in cell-cell coupling. In a retinal ischaemiareperfusion model both systemic delivery and intraocular injection of Peptide5 reduced vascular leak and inflammation, promoting almost total neuronal survival [9,27,30].…”

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

“…However the most commonly used synthetic polymers consist in aliphatic polyesters such as polycaprolactone (PCL) polylactic acid (PLA), polyglycolic acid (PGA), and PLGA, due to the advantages that characterized such polymers, as stated in the previous section. [80–82] As discussed in the prior section, the desired drug release profile can be engineered through varying the molecular weight of the polymer and copolymer formulation (as well as other formulation variables), allowing the tuning of the duration of release that can range from weeks to months. [83] One example of PLGA microspheres that are capable of providing one-month of release of an ophthalmic medication following subconjunctival injection has been recently developed.…”