Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Methoxy Poly(ethylene glycol)-b-Poly(d,l-Lactide) Polymeric Micelles Encapsulating Alpinumisoflavone Extracted from Unripe Cudrania tricuspidata Fruit

Abstract

Alpinumisoflavone, a major compound in unripe Cudrania tricuspidata fruit is reported to exhibit numerous beneficial pharmacological activities, such as osteoprotective, antibacterial, estrogenic, anti-metastatic, atheroprotective, antioxidant, and anticancer effects. Despite its medicinal value, alpinumisoflavone is poorly soluble in water, which makes it difficult to formulate and administer intravenously (i.v.). To overcome these limitations, we used methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG-b-PLA) polymeric micelles to solubilize alpinumisoflavone and increase its bioavailability, and evaluated their toxicity in vivo. Alpinumisoflavone-loaded polymeric micelles were prepared using thin-film hydration method, and their physicochemical properties were characterized for drug release, particle size, drug-loading (DL, %), and encapsulation efficiency (EE, %). The in vitro drug release profile was determined and the release rate of alpinumisoflavone from mPEG-b-PLA micelles was slower than that from drug solution, and sustained. Pharmacokinetic studies showed decreased total clearance and volume of distribution of alpinumisoflavone, whereas area under the curve (AUC) and bioavailability were significantly increased by incorporation in mPEG-b-PLA micelles. In vivo toxicity assay revealed that alpinumisoflavone-loaded mPEG-b-PLA micelles had no severe toxicity. In conclusion, we prepared an intravenous (i.v.) injectable alpinumisoflavone formulation, which was solubilized using mPEG-b-PLA micelles, and determined their physicochemical properties, pharmacokinetics, and toxicity profiles.

Optimization and Pharmacokinetic Evaluation of Synergistic Fenbendazole and Rapamycin Co-Encapsulated in Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles

“… 45 In addition, they are biodegradable, biocompatible, nontoxic, and have high vascular permeability at the target site because they are small (< 100 nm). 46 , 47 We used three candidate polymers to design an optimal micelle formulation. Methoxy poly(ethylene glycol)- b -poly(caprolactone) (mPEG- b -PCL) is a diblock copolymer with a hydrophobic PCL core and a hydrophilic PEG shell.…”

Recent Advances and Challenges in Controlling the Spatiotemporal Release of Combinatorial Anticancer Drugs from Nanoparticles

“…Nanoparticles have been widely used as vehicles for cancer treatment because of their several advantages, and various nanocarriers such as liposomes, polymeric micelles, silica nanoparticles, chitosan nanoparticles, and protein nanoparticles are being developed [11][12][13][14][15]. The encapsulation of drugs using nanocarriers can help solubilize various poorly water-soluble drugs using nanocarriers with amphiphilic properties [16]. In addition, it is possible to protect drugs through nano-encapsulation or via nanoparticle uptake through endocytosis [17].…”

Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Soluplus® Polymeric Micelles Encapsulating Fenbendazole

“…The mPEG- b -PLA micelle can hold and carry multiple drugs [ 26 ]. This polymer can also remain in circulation for a long time and has low toxicity [ 27 ]. In cancer treatment, the occurrence of drug resistance owing to P-glycoprotein (P-gp) overexpression is a serious problem [ 28 ].…”