A preliminary study on MeO‐PEG‐PLGA‐PEG‐OMe nanoparticles as intravenous carriers

Abstract

To develop an intravenous nanoparticle delivery system for a cancer drug (i.e., DHAQ, mitoxantrone), the synthesis of a biodegradable polyester polymer with hydrophilic polyethylene glycol chains, preparation of DHAQ-loaded nanoparticles from such polymer and biodistribution of the drug-loaded particles were investigated in this article. Biodegradable monomethoxy poly(ethylene glycol)-poly (lactide-co-glycolide)-monomethoxy poly(ethylene glycol) (MeO-PEG-PLGA-PEG-OMe, PELGE) copolymers were synthesized by ring-opening polymerization as the drug carriers. A double emulsion method with dextran-70 as an emulsifier was employed to prepare the nanoparticles. DHAQ-PELGE nanoparticles and free DHAQ were employed for the in vivo biodistribution studies after intravenous administration through the tail veins in mice. At various time intervals, the mice were sacrificed and several organs and tissues harvested, including hearts, livers, spleens, lungs, kidneys, and blood. The DHAQ concentrations in the collected tissues and plasmas were determined using high performance liquid chromatography. The DHAQ concentrations in mice plasmas in the experimental groups were significantly higher than those in the control group and 3.72% of total administrations dosages (TAD) of these particles with DHAQ remained in circulation even 96 h after intravenous injection. Compared with the free DHAQ, DHAQ-loaded PELGE nanoparticles had longer circulation properties. Further research should be done for intravenous injection of this material as drug carriers.

PLGA's Plight and the Role of Stealth Surface Modification Strategies in Its Use for Intravenous Particulate Drug Delivery

“…Polyethylene glycol was the first surface coating used to design long-circulating PLGA-based particles and remains the most investigated compound to date. [63] Once PEG has been engineered to attach to the hydrophobic PLGA surface, a variety of favorable physicochemical characteristics can be observed: namely, nearneutral zeta potentials, [64] a dense hydrated brush layer forming the outer shell, [65,66] steric stabilization in biological media, [67,68] and improved entrapment of water-soluble substances. [69,70] Depending on factors, such as PEG corona thickness, brush density, and molecular weight, different stealth properties will be observed.…”

Stimuli-Responsive InjectableIn situ-Forming Hydrogels for Regenerative Medicines

“…Injectable in situ-forming hydrogel using PLGA-PEG-PLGA end-groupfunctionalized triblock copolymers have also been developed. [242][243][244][245][246] These copolymers are barbell shaped and formed through the introduction of alkyl, ester, or histidine groups. Macroscopic gelation is influenced by inter-and intramolecular interactions between the end groups.…”

Drug-loaded nano-microcapsules delivery system mediated by ultrasound-targeted microbubble destruction: A promising therapy method

“…Poly(lactic-co-glycolic acid) (PLGA) copolymer (12,13), one of the most commonly used biodegradable polyester materials, may be used in all types of drug-loaded nano-microcapsules embedding proteins (3), amino acids (3), genes (3), vaccines (9), antigens and growth factors (4). PLGA has been approved by the FDA for human medical use, and is non-toxic and harmless (10,14,15). Its crystallinity, solubility and water absorption capacity are regulated by modifying the proportion of polylactic and polyglycolic acid to control the rate of degradation, in order to meet the needs of the release of different embedded drugs (16)(17)(18)(19).…”