Novel PEG-graft-PLA nanoparticles with the potential for encapsulation and controlled release of hydrophobic and hydrophilic medications in aqueous medium

Abstract

This study concerns the encapsulation and controlled release of both hydrophobic and hydrophilic medications with one polymer, which are delivered together as a combined therapy to treat diseased tissue. To test our hypothesis that the novel PEG-graft-PLA (PEG, polyethylene glycol; PLA, polylactic acid) can deliver both the hydrophobic and hydrophilic medications on account of its amphiphility, charge, and graft structure, PEG-graft-PLA (molecular weight of PEG = 1900) with very low critical micelle concentration was synthesized. One hydrophilic (insulin) and one hydrophobic (naproxen) model medication were loaded in separately during its self-assembly in aqueous solution. The resulting nanoparticles (NPs) were narrowly distributed and spherical, with average particle size around 200 nm, zeta potential >−10 mV, and encapsulation efficiency >50%. The NPs realized controlled release of insulin and naproxen for over 24 and 160 hours, respectively. Specifically, the bioactivity of the insulin released from the NPs was maintained. Owing to encapsulation, both for hydrophobic and hydrophilic medicines, and NPs obtained with similar size and zeta potential, as well as maintenance of bioactivity of loaded protein, we expect the applications of PEG-graft-PLA NPs in combination therapy.

Poly(lactic acid)–poly(ethylene glycol) nanoparticles provide sustained delivery of a Chlamydia trachomatis recombinant MOMP peptide and potentiate systemic adaptive immune responses in mice

“…Here we employed ethyl acetate, an organic solvent of PLA, which in the presence of PEG acts as a surfactant in an ethyl acetate-water system 29 and PVA as the emulsifying agent for fabricating stable PLA-PEG nanoparticles. PLA-PEG-M278 nanoparticles had a −16 mV zeta potential, 73–100 nm size and ~60% encapsulation efficiency, thus corroborating the > −10 mV zeta potential and > 50% encapsulation efficiency attained for other PLA-PEG nanoparticles fabricated with ethyl acetate 28–30 . The inability of PLA-PEG-M278 to affect macrophages viability may have resulted from their non-toxic properties or alternatively to their rapid uptake and processing by macrophages, henceforth greater viability.…”

“…PLA-PEG offers an attractive alternative to conventional adjuvants as a vaccine-delivery system because it can augment the immunogenicity of proteins by providing their controlled slow release to the immune system 1,2,26 . Moreover, PLA-PEG can enhance the protein loading capacity, reduce its burst effect, prevent degradation, and increase the circulation time and bioavailability of proteins without altering their spatial configuration 27,28 . In the present study, we exploited PLA-PEG immune-potentiating and controlled slow release properties as a vaccine-delivery system for M278, a C. trachomatis MOMP peptide.…”

Novel Polymeric Nanoparticles for Intracellular Delivery of Peptide Cargos: Antitumor Efficacy of the BCL-2 Conversion Peptide NuBCP-9

“…Moreover, our results demonstrate that release of NuBCP-9 over time is enhanced by increases in PEG chain length, a finding in concert with greater flexibility, hydrophilicity and hydration of the NP. In turn, the rate of diffusion increases, as does release of the peptide from the NP matrix (20, 45-48). Thus, for NuBCP-9 and potentially other peptide drugs, these findings indicate that PEG chain length is of importance for both loading in and release from polymeric NPs.…”

Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo

“…However, because of its weak hydrophilicity, excessively long degradation time, and low drug loading of polar drugs [20, 21], PLA’s applications are limited. To overcome these shortcomings, PEG was combined with PLA to form a block co-polymer in this study [22–24]. Most kinds of cancer including ovarian cancer over-express FA receptor, and FA was demonstrated to be an excellent tumor-targeting molecule in nano-carrier drug delivery systems [25, 26].…”