PLGA from PolySciTech used in development of novel hydrogel-supported long-acting injectable formulation

 

All medicinal molecules administered to a patient will eventually be removed from the body by a variety of clearance mechanisms (e.g. excreted in urine, destroyed in the liver, exhaled through lungs etc.) and the rate of this clearance is described as the biological half-life of the particular molecule which is usually in the order of magnitude of minutes to hours. For an injected medicine, this means that to keep a therapeutic dose in a patient there would have to be repeating doses to replace the medicine that is cleared by the body. This is inconvenient and difficult to maintain compliance as patients generally don’t enjoy being repeatedly stabbed with a needle so it is better to provide a long-acting injectable formulation which requires only a single injected of the drug molecule encapsulated in a material which slowly releases the drug out into the bloodstream over an extended period of time. Recently, researchers from Kangwon National University, Chonnam National University, Seoul National University (Korea), Terasaki Institute for Biomedical Innovation, and University of California, Los Angeles, used PLGA (AP059) from PolySciTech (www.polyscitech.com) to create donepezil-loaded microparticles. These particles were subsequently loaded into a novel HA hydrogel system to create a long-acting injectable. This research holds promise to provide for improved drug-release systems in the future. Read more: Hwang, ChaeRim, Song Yi Lee, Han-Jun Kim, KangJu Lee, Junmin Lee, Dae-Duk Kim, and Hyun-Jong Cho. "Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery." Carbohydrate Polymers (2021): 118104. https://www.sciencedirect.com/science/article/pii/S0144861721004914

“Highlights: Hyaluronic acid-dopamine-polyethylene glycol (HD-PEG) was synthesized and identified. HD-PEG was threaded with alpha-cyclodextrin (α-CD) and pH was adjusted to 8.5. Polypseudorotaxane structure and polydopamine bond-based hydrogel was fabricated. Donepezil-loaded microspheres were embedded in hydrogel system for sustained release. Rheological features of injectable hydrogel were tuned for slow biodegradation. Abstract: Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection. Keywords: Crosslinked hydrogel Polypseudorotaxane Polydopamine Single syringe injection Slow biodegradation Sustained drug release”