Optimization and Evaluation of Poly(lactide-co-glycolide) Nanoparticles for Enhanced Cellular Uptake and Efficacy of Paclitaxel in the Treatment of Head and Neck Cancer

Abstract

The particle size (PS) and encapsulation efficiency (EE%) of drug-loaded nanoparticles (NPs) may inhibit their cellular uptake and lead to possible leakage of the drug into the systemic circulation at the tumor site. In this work, ultra-high paclitaxel-loaded poly(lactide-co-glycolide) NPs (PTX-PLGA-NPs) with ultra-small sizes were prepared and optimized by adopting the principles of quality by design (QbD) approach. The optimized PTX-PLGA-NPs showed ultra-small spherical particles of about 53 nm with EE% exceeding 90%, a relatively low polydispersity index (PDI) of 0.221, an effective surface charge of −10.1 mV, and a 10-fold increase in the in vitro drug release over 72 h relative to free drug. The cellular viability of pharynx carcinoma cells decreased by almost 50% in 24 h following treatment with optimized PTX-PLGA-NPs, compared to only 20% from the free drug. The intracellular uptake of PTX-PLGA-NPs was highly favored, and the antitumor activity of PTX was remarkably improved with a reduction in its half maximal inhibitory concentration (IC50), by almost 50% relative to free drug solution. These results suggest that the optimal critical formulation parameters, guided by QbD principles, could produce PLGA-NPs with remarkably high EE% and ultra-small PS, resulting in enhanced cellular uptake and efficacy of PTX.

A Tri-Stimuli Responsive (Maghemite/PLGA)/Chitosan Nanostructure with Promising Applications in Lung Cancer

“…All the characteristics bands of the polymers (CS and PLGA) were present in the spectrum of these magnetopolymeric particles, hence demonstrating that the shell observed in Figure 2 corresponded well to the PLGA and CS shells onto the γ -Fe 2 O 3 nuclei. Chemical groups identified in the spectra were: (A) overlapped stretching vibrations from N–H and O–H bonds (at ≈3400 cm −1 ) [ 109 , 110 , 111 ]; (B) C–H bond stretching vibration of −CH, −CH 2 , and −CH 3 groups (at ≈2850 cm −1 ) [ 109 , 110 , 112 ]; (C) C = O bond stretching vibration of a carboxylic acid (at ≈1750 cm −1 ), probably from the PLGA shell [ 111 , 113 , 114 ]; (D) C = O bond stretching vibration of an amide group, presumably from the CS coating (≈1630 cm −1 ) [ 110 , 112 , 115 ]; (E) asymmetric CH 2 bending vibration (at ≈1450 and ≈1380 cm −1 ) [ 110 , 112 , 113 ], and O–H bending vibration, probably from the carboxylic group in the PLGA shell (at ≈1420 cm −1 ) [ 104 ]; (F) C–O bond stretching vibrations from a −OH group (at ≈1280 cm −1 ) [ 116 ]; (G) C–O bond stretching vibration from the carboxylic group in PLGA (at ≈1160 cm −1 ) [ 104 , 116 ]; (H) C–O–C bond stretching vibration from PLGA (at ≈1130 and ≈1080 cm −1 ) [ 97 , 104 , 112 ]; (I) medium band characteristic of alkanes (at ≈890 cm −1 ) [ 117 ]; (J) CH rocking vibration characteristic of –CH long chains (at ≈800 cm −1 ) [ 104 , 117 ]; and, (K) Fe–O bond vibration from pure iron oxide NPs (at ≈560 cm −1 ) [ 104 , 118 , 119 ].…”

In Situ-Forming Microparticles for Controlled Release of Rivastigmine: In Vitro Optimization and In Vivo Evaluation

“…SAIB, a highly lipophilic water-insoluble sugar and an FDA-approved food additive, was used as a non-polymeric matrix former in the fabrication of RV-ISM systems to test its ability to control the drug release in situ, while making use of its undeniable favorable properties, such as its high solubility in a wide range of organic solvents which result in the formation of low-viscosity solutions compared to more common polymers, in addition to its biocompatibility, biodegradability, in vivo tolerability and low cost [ 23 ]. The more expensive and more viscous PLGA is, an FDA-approved biodegradable and biocompatible copolymer, the more widely it is used in the fabrication of drug delivery systems (DDS) that enhance the pharmaceutical characteristics of many drugs [ 40 ]. The attractive features of PLGA-based DDS, such as small size, high structural integrity, colloidal stability, ease of fabrication, controlled release capability and surface functionalization, make them very attractive therapeutic delivery vehicles [ 41 , 42 ].…”

Engineered Sumoylation-Deficient Prdx6 Mutant Protein-Loaded Nanoparticles Provide Increased Cellular Defense and Prevent Lens Opacity

“…In this work, we used 6-week-old SCR rats to inject TAT-HA-Prdx6 analog-NPs in the SCR eyes. These animals develop posterior cortical cataracts at 9 weeks old and mature or severe cataracts after 10 week onwards (S. Shumiya, 1995) [ 71 ]. Before treatment, four-week-old cataractous (Cat+) and noncataractous (Cat-) SCRs were identified via performing genomic polymerase chain reaction (PCR) with genomic DNA from the rat’s tails and primers specific to lanosterol synthetase (Lss) [ 72 ].…”

“…Subconjuctival Administration of TAT-HA-Prdx6 Analog-NPs Prevented Lens Opacity and Delayed the Progression of Cataract Formation in SCRs While in vitro studies conducted would be very useful for documenting the characterization and cytoprotective potential of formulated Prdx6-NPs, we acknowledge that the results obtained from the in vitro studies could only be considered if they could be reproduced in vivo. Considering the wide range of protective and survival activities of Prdx6 [3,4,8,9,14,15,34,39,[91][92][93][94][95][96][97], we chose to use the SCR (a model for cataract), which shows a spectrum of biochemical and morphological changes, including oxidative-induced cell biological changes during the progression of cataract [14,71,[98][99][100]. Since the SCRs generally develop cataracts at the 9th week, we used 6-week-old rats, administering TAT-HA-Prdx6 analog-NPs by the subconjuctival route.…”