Investigating a Curcumin-Loaded PLGA-PEG-PLGA Thermo-Sensitive Hydrogel for the Prevention of Alzheimer’s Disease

Abstract

In Alzheimer’s disease (AD), the most common cause of dementia, patients generally forget to take pills or skip medication due to side effects, affecting the treatment efficacy. In this study, we combined a poly(lactic-co-glycolic acid), (PLGA)-poly(ethylene glycol), and (PEG)-PLGA thermo-sensitive hydrogel with curcumin (PGC) to deliver an intramuscular injection that could continuously release curcumin and maintain it at a constant level in blood to prevent AD development or progression. We evaluated the drug release profile and cytotoxicity of PGC and its effects on AD pathology through in vitro and in vivo studies and on cognitive function through an aluminum-chloride-induced AD rat model. In the in vitro study, PGC exhibited a lack of cytotoxicity, excellent anti-inflammatory and antioxidant properties, and microglial modulation. In the Morris water maze test, the PGC injection-administered AD rats presented well-focused searching behavior with the shortest swimming path and longest retention times in the quadrant where the platform was initially located. Furthermore, PGC reduced amyloid-beta aggregation and deposition and significantly increased hippocampal activity. This study demonstrated that intramuscular PGC injection can effectively prevent AD development or progression in rats without inducing toxicity; therefore, this strategy could help overcome the present challenges in AD management in humans.

Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review

“…Lin et al [ 57 ] evaluated the combination of PLGA-PEG-PLGA thermo-sensitive hydrogel with CUR (PGC) in preventing and decreasing the progression of AD. In vitro studies demonstrated that PGC did not exert cytotoxicity but had excellent anti-inflammatory and antioxidant properties and microglial modulation.…”

Next-Generation Hydrogels as Biomaterials for Biomedical Applications: Exploring the Role of Curcumin

“…This is the result of various parameters including enhanced mechanical characteristics and degradation of hydrogels in a finely tuned, highly controlled manner. The most frequently investigated natural polymers used for hydrogel preparation are chitosan, dextrin, lignin, hyaluronic acid, carrageenan, tannic acid, alginic acid, and collagen. − Synthetic and semisynthetic polymers can also be used for hydrogel preparation . These polymers mainly include polyethylene glycol (PEG), poly lactic acid, poly lactic coglycolic acid (PLGA), and poly vinyl alcohol (PVA) as well as carboxymethyl cellulose (CMC), hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose. − Based on the monomers used for the preparation of the polymeric network, hydrogels may contain homo-polymeric, co-polymeric, or multi-polymeric networks. , While polymerization of a single type of monomers results in the formation of homo-polymeric networks, co-polymeric or multi-polymeric networks result from the polymerization of two or more types of monomers. , …”

“…The biocompatibility, swelling behavior, and low toxicity of hydrogels make them suitable candidates for biomedical applications including drug delivery. − One of the major obstacles for drug development is the administration of hydrophobic drugs with low solubility in aqueous media . Considering the unique properties of hydrogels, this delivery system can be used as a promising vehicle for formulation of low soluble hydrophobic therapeutics. ,, This approach enables researchers and patients to apply these therapeutic agents via oral, topical or parenteral routes of administration …”

“…13−20 Synthetic and semisynthetic polymers can also be used for hydrogel preparation. 21 These polymers mainly include polyethylene glycol (PEG), poly lactic acid, poly lactic coglycolic acid (PLGA), and poly vinyl alcohol (PVA) as well as carboxymethyl cellulose (CMC), hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose. 21−29 Based on the monomers used for the preparation of the polymeric network, hydrogels may contain homo-polymeric, co-polymeric, or multi-polymeric networks.…”

“…38 Considering the unique properties of hydrogels, this delivery system can be used as a promising vehicle for formulation of low soluble hydrophobic therapeutics. 21,39,40 This approach enables researchers and patients to apply these therapeutic agents via oral, topical or parenteral routes of administration. species.…”