Effects of Particle Geometry for PLGA-Based Nanoparticles: Preparation and In Vitro/In Vivo Evaluation

Abstract

The physicochemical properties (size, shape, zeta potential, porosity, elasticity, etc.) of nanocarriers influence their biological behavior directly, which may result in alterations of the therapeutic outcome. Understanding the effect of shape on the cellular interaction and biodistribution of intravenously injected particles could have fundamental importance for the rational design of drug delivery systems. In the present study, spherical, rod and elliptical disk-shaped PLGA nanoparticles were developed for examining systematically their behavior in vitro and in vivo. An important finding is that the release of the encapsulated human serum albumin (HSA) was significantly higher in spherical particles compared to rod and elliptical disks, indicating that the shape can make a difference. Safety studies showed that the toxicity of PLGA nanoparticles is not shape dependent in the studied concentration range. This study has pioneering findings on comparing spherical, rod and elliptical disk-shaped PLGA nanoparticles in terms of particle size, particle size distribution, colloidal stability, morphology, drug encapsulation, drug release, safety of nanoparticles, cellular uptake and biodistribution. Nude mice bearing non-small cell lung cancer were treated with 3 differently shaped nanoparticles, and the accumulation of nanoparticles in tumor tissue and other organs was not statistically different (p > 0.05). It was found that PLGA nanoparticles with 1.00, 4.0 ± 0.5, 7.5 ± 0.5 aspect ratios did not differ on total tumor accumulation in non-small cell lung cancer.

Elucidating shape-mediated drug carrier mechanics of hematite nanomaterials for breast cancer therapeutics

“…43 We speculate that the ellipsoidal nanoparticles with a high aspect ratio may improve the adhesion on the cell membrane, inducing the micropinocytosis pathway as discussed before. 44–46 Modelling studies reported that the elongated nanomaterials would initially bind to the cells in an inclined tip insertion state and swing nonuniformly, subsequently progressing to the upright restricted rotation with insertion, followed by free rotation thus facilitating the cellular uptake veiling. 47 Thus, we conclude that due to the high cellular uptake rate, the EHNP exhibited excellent anticancer efficacy with less IC 50 concentration compared to SHNP and free drugs.…”

Size-Dependent Polymeric Nanoparticle Distribution in a Static versus Dynamic Microfluidic Blood Vessel Model: Implications for Nanoparticle-Based Drug Delivery

“…21 Indeed, several studies highlight the importance of NP physicochemical properties in determining their interaction with cells. 72,73 Despite the mechanism of NP transcytosis being still unclear, NPs tend to be mainly internalized by clathrinmediated endocytosis (CME), caveolin-mediated endocytosis (CVME), or micropinocytosis. 74 Subsequently, the cargo of NPs is translocated through the cytoplasm and released by an exocytosis mechanism.…”

“…Thus, the rod shape could reduce the NP association with the endothelium compared with the spherical shape . Indeed, several studies highlight the importance of NP physicochemical properties in determining their interaction with cells. , …”

“… 21 Indeed, several studies highlight the importance of NP physicochemical properties in determining their interaction with cells. 72 , 73 …”

Formulation, optimization and characterization of raloxifene hydrochloride loaded PLGA nanoparticles by using Taguchi design for breast cancer application

“…In recently, Kaplan M and colleagues developed spherical PLGA NPs by double emulsion solvent evaporation technique. Authors reported spherical NPs exhibited higher cellular uptake in A549 cancer cell than elliptical and rod shape NPs (Kaplan et al, 2023).…”