Tuning the Size of Poly(lactic‐co‐glycolic Acid) (PLGA) Nanoparticles Fabricated by Nanoprecipitation

Abstract

Polymeric nanoparticles (PNPs) are promising drug carriers in cancer treatment. Size of the particles has a significant impact on drug loading, in vivo distribution, extravasation, intratumor diffusion and cell uptake, and thus is critical for the successful development of a drug delivery regime. However, methods for manufacturing PNPs of defined size are yet to be established. The goal of this study is to establish a method that can be used to fabricate PNPs with controlled size. The factors that could impact the size of PNPs fabricated by nano-precipitation are systematically investigated. The factors studied include polymer concentration, organic solvent, temperature, aqueous phase ionic strength, organic phase injection rate, aqueous phase agitation rate, gauge of the needles, and final polymer concentration. Polymer concentration, the choice of organic solvent, temperature, and the ionic strength of the aqueous phase are shown to have a significant impact on the size of PNPs, and the effect of these factors can be attributed to a single parameter, the diffusion coefficient of the solvent in water, D pw . It is possible that by tightly control these four parameters, nanoparticles with highly predictable and desirable size with narrow size distribution can be fabricated.

Sustained in vitro interferon-beta release and in vivo toxicity of PLGA and PEG-PLGA nanoparticles

“…Zeta potential values of the nanoparticles (17.7 mV and 18.8 mV for PLGA-IFN and PEG-PLGA-IFN, respectively) might not indicate stable suspension of the nanoparticles, nevertheless, their agglomeration was not observed, which must be due to the steric repulsion resulted from the PVA adsorption that impedes the aggregation. These values are in accordance with the zeta potential result of À15 mV found by Huang et al 21 using 10 mg ml À1 polymer concentration similar to our optimal experiments. They also stated that the zeta potential depended on the polymer concentration.…”

“…To prepare blank nanoparticles without BSA, the nanoprecipitation method was utilized. 21 5 mg of Resomer 752 H or Resomer RGP t 50106 was dissolved in 0.5 ml acetone under magnetic stirring. A water phase with a volume of 2.0 to 4.0 ml was composed of an aqueous solution (1.0% w/v) of the emulsifying agent PVA.…”

Nanoparticle-mediated local delivery of pioglitazone attenuates bleomycin-induced skin fibrosis

“…We targeted the particle size 200-400 nm, hoping to enable both the cellular uptake of the particles and retention at the lesion site as a depot drug. Generally, cells internalize particles of 100-200 nm via receptor-mediated endocytosis and larger particles via phagocytosis [23]. Nonprofessional phagocytes may exhibit some phagocytic activity, but to a lower extent [24].…”

“…In addition to the cellular uptake, the distribution of nanoparticles in the body after administration also depends on the nanoparticle size [23]. In general, small drug molecules (<1 kDa) are thought to be preferentially absorbed by the blood capillaries after subcutaneous injection.…”

Role of self‐assembly conditions and amphiphilic balance on nanoparticle formation of PEG‐PDLLA copolymers in aqueous environments

“…The ability to modulate, on demand, the final NP size and stability simply through tuning the formulation parameters is a potential strategy to achieve optimum physical characteristics without requiring the synthesis of new polymers each time. While investigations into the self‐assembly behavior of PLGA and PCL polymers have been analyzed and reported in detail in previous literature, as well as one example of a PEGylated block copolymer (poly(ethylene glycol)‐ b ‐poly( N ‐2‐benzoyloxypropyl methacrylamide) (mPEG‐ b ‐p(HPMA‐Bz)), to our knowledge, this process has not been explored in detail for PEG‐PDLLA polymers . Therefore, to provide important insights into the tunable parameters that influence self‐assembly of these clinically relevant materials, this work presents a complete study of NP formation and assessment of stability.…”