Micelle-templated, poly(lactic-<em>co</em>-glycolic acid) nanoparticles for hydrophobic drug delivery

Abstract

Purpose Poly(lactic- co -glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches. Methods Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, “PolyDots”), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene- b -ethylene oxide) (PS- b -PEO) micelles. Results PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS- b -PEO micelles (ie, ~7%). Increasing the PLGA:PS- b -PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray. Conclusion Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications.

<p>Comparative Encapsulation Efficiency of Lutein in Micelles Synthesized via Batch and High Throughput Methods</p>

“…Additionally, all vehicles experienced a slight increase in diameter with lutein addition, which suggests lutein encapsulation. 41 Particle diameter increase is characteristic of drug addition to the nanoparticle and is commonly associated with evidence of encapsulation. However, there is no expected correlation between loaded carrier size among different systems and encapsulation efficiency, as final carrier size is dictated by amphiphile geometry and size.…”

“…Previously, we have observed virtually no release in PBS over 7 days and that release is “smart”, occurring primarily as a result of endosomal rupture. 41 Thus, this study focused on the effect of synthesis method on lutein encapsulation across the three delivery vehicles. II sonication processes uniformly resulted in lower encapsulation efficiencies than scalable EM-NP processes ( Table 2 ), suggesting that the kinetically driven nature of EM-NP may allow for greater drug loading.…”

“…Histogram plots were fitted using a three parameter logarithmic equation via SigmaPlot 14.0, as lognormal distribution is expected for drug-loaded micelles. 41 Particle size mean, standard deviation, and polydispersity were determined using the following equations:…”

Systemic Review of Biodegradable Nanomaterials in Nanomedicine

“…A micelle is defined as a collection of amphiphilic molecules that can self-assemble in water into a spherical vesicle [19]. Micelles can be formed by either lipid-or polymer-based amphiphilic molecules [20][21][22]. Lipid-based micelles are composed of small molecules that have a hydrophilic head group and a hydrophobic tail, which is the hydrocarbon portion of long fatty acids [23].…”

“…Meanwhile modifications of the nanoparticles have also been made for better delivery efficiency. For example, micelle-templated Polylactic-co-glycolic acid (PLGA) nanoparticles have been developed for hydrophobic drug delivery with increased stability and loading capacity [21].…”