Influence of PEGylation on PLGA nanoparticle properties, hydrophobic drug release and interactions with human serum albumin

Abstract

Objective To evaluate the impact of PEG content on poly(lactic‐co‐glycolic acid) (PLGA) NP physicochemical properties, hydrophobic drug release (rifampicin as a model drug) and human serum protein binding. Methods Rifampicin loaded and unloaded nanoparticles with PEG content of 0–17% (w/w) were prepared by an emulsification–evaporation technique. Nanoparticles were characterized for size, zeta potential and morphology. PEGlyation was confirmed using proton nuclear magnetic resonance (1H NMR). Fluorescence spectroscopy and dynamic light scattering were used to determine nanoparticle‐protein binding, binding constants and stability of nanoparticles in human serum, respectively. Drug loading and release were determined by UV‐VIS spectroscopy and drug release data was mathematically modelled. Key findings A NP PEG content of 17% w/w significantly retarded release of rifampicin from PLGA NPs and altered kinetics of drug release. Stern–Volmer (Ksv) protein binding constants decreased upon PEG incorporation. A 2% w/w PEG was sufficient to significantly reduce protein binding extent to PLGA NPs and maintain particle size distributions. Conclusion The ability to fine tune drug release and formation of protein corona around nanoparticles is crucial to formulation scientists. This study suggests that PLGA NPs with low PEG content might be suitable for extended circulation and rapid drug release and that higher PEG content retards hydrophobic drug release.

A Novel Sustained Anti-Inflammatory Effect of Atorvastatin—Calcium PLGA Nanoparticles: In Vitro Optimization and In Vivo Evaluation

“…Association of polymeric networks modified after PEG addition might produce NPs with smaller diameter [12,19,46]. As our model drug At-Ca is highly hydrophobic, its entrapment will efficiently increase into PLGA hydrophobic core with no tendency for diffusion out to the external hydrophilic PEG surface [47]. Additionally, PEG controls the prolonged release of At-Ca NPs for 72 h due to reducing drug release rates and slowing down its diffusion outside the nanovesicle [47].…”

“…As our model drug At-Ca is highly hydrophobic, its entrapment will efficiently increase into PLGA hydrophobic core with no tendency for diffusion out to the external hydrophilic PEG surface [47]. Additionally, PEG controls the prolonged release of At-Ca NPs for 72 h due to reducing drug release rates and slowing down its diffusion outside the nanovesicle [47]. PEG aids to exhibit sustained anti-inflammatory action of At-Ca PLGA NPs.…”

Physicochemical and Biological Evaluation of Curdlan-Poly(Lactic-Co-Glycolic Acid) Nanoparticles as a Host-Directed Therapy Against Mycobacterium Tuberculosis

“…As the NPs are not protected with polyethylene glycol, they experience a higher extent of protein binding. 27 Both NP size and size distribution remain relatively constant over a 72-h period, whilst the zeta potential of the NPs increased over time. Statistical analysis confirmed there was a significant difference between the PDI observed at the start and after 72 h for the various NPs (p < 0.05).…”

“…This is due to the presence of proteins in the media resulting in the formation of a protein corona which affects the NP size, PDI and zeta potential. As the NPs are not protected with polyethylene glycol, they experience a higher extent of protein binding 27 . Both NP size and size distribution remain relatively constant over a 72-hour period, whilst the zeta potential of the NPs increased over time.…”

pH-Triggered Poly(ethylene glycol)–Poly(lactic acid/glycolic acid)/Croconaine Nanoparticles-Assisted Multiplexed Photoacoustic Imaging and Enhanced Photothermal Cancer Therapy

“…We believe these biocompatible and bioeliminable NPs represent a new generation of nanotheranostic platform to perform diagnosis and anticancer treatment synchronously. 46,47 Briefly, Mal−PEG−PLGA (8 mg) and Croc 815 dye (4 mg) were codissolved in chloroform (200 μL). The organic phase was added and emulsified with a PVA (1%, w/v, 1.0 mL) aqueous solution using probe sonicator TL-ST150 (Tenlin China).…”