PEGylation strategies for active targeting of PLA/PLGA nanoparticles

Abstract

This work evaluates various techniques for the incorporation of poly(ethylene glycol) (PEG) onto biodegradable nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) or poly(lactic acid) (PLA) with the purpose of providing a functional site for surface conjugation of targeting agents and for improving surface properties. The techniques compared were based on NP preparation with blends of PLGA and poloxamer or with block copolymers of PLGA/PLA with PEG. Blending of PLGA with poloxamer 407 resulted in the incorporation of the latter to up to a 43 wt % content. Direct conjugation of heterofunctional NH2-PEG-COOH to the surface of premade NPs was not highly effective. Preparation of copolymers of PLGA with PEG was determined to be more effective and versatile by polymerization of lactide and glycolide dimers onto the hydroxyl group of heterofunctional OH-PEG-COOH than by conjugation of the premade polymers with carbodiimide chemistry. NPs prepared with these copolymers confirmed the surface localization of PEG and proved to be useful for conjugation of mouse immumoglobulin as a model targeting agent.

Spermidine-mediated poly(lactic-<em>co</em>-glycolic acid)&nbsp;nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis

“…36,37 In this regard, NPs based on amphiphilic copolymers of polyethylene glycol (PEG; as a hydrophilic) and PLGA have already been approved by the US Food and Drug Administration (FDA), and PEG-PLGA copolymers are safe and nontoxic after hydrolysis in vivo. 38 In former work at our laboratory, we found that AKF-loaded PLGA microspheres improved the curative effect of AKF in treating acute lung injury via intravenous administration. 39 It can be concluded that the extent of drug accumulation in the lung is closely related to therapeutic efficacy, while it is worth noting that large particles might cause pulmonary capillary embolization, which induces severe side effects.…”

Poly(lactic acid) blends in biomedical applications

“…PEG confined to the surface of the particles improves circulation time in vivo and site specific targeting [115,116]. Novel delivery technologies can be beneficial for drugs with narrow therapeutic index…”

PEGylation of magnetic poly(glycidyl methacrylate) microparticles for microfluidic bioassays

“…Consequently, a rapid and simple method to improve particle surface properties is required. PEG was chosen for its antifouling properties, which have been so far deeply investigated in a relation with proteins, cells, DNA [53][54][55]58 etc.…”

“…There was no significant difference in BSA repellence between CH 3 -PEG 30,000 -NH 2 -PGMA and CH 3 -PEG 2,000 -NH 2 -PGMA microspheres, and the PEG corona around the microspheres dramatically decreased NSA in both cases. [57][58][59] . In our study, improved antifouling properties of magnetic microspheres due to PEGylation enabled their prospective use as a carrier for magnetic separation from complex biological material.…”