Solid lipid nanoparticles of paclitaxel strengthened by hydroxypropyl-β-cyclodextrin as an oral delivery system

Abstract

The objective of this study was to evaluate the potential of surface-modified paclitaxel (PTX)-incorporated solid lipid nanoparticles with hydroxypropyl-β-cyclodextrin (smPSH). The smPSH released 89.70 ± 3.99% of its entrapped PTX within 24 h when placed in dissolution medium containing sodium lauryl sulfate. The cellular uptake of PTX from smPSH in Caco-2 cells was 5.3-fold increased compared to a PTX solution based on a Taxol formulation. Moreover, smPSH showed an increased cytotoxicity compared to PTX solution. In addition, AUC (5.43 µg•h/ml) and Cmax (1.44 µg/ml) of smPSH were higher than those (1.81 µg•h/ml and 0.73 µg/ml) of PTX solution. The drug concentration of smPSH (11.12 ± 4.45 ng/mg of lymph tissue) in lymph nodes was higher than that of the PTX solution (0.89 ± 0.75 ng/mg of lymph tissue), suggesting that more PTX was transported to the lymphatic vessels in the form of smPSH. In conclusion, smPSH have a potential as an alternative delivery system for oral administration of PTX.

Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-β-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection

“…Therefore, the small PSC particle size might improve the rate and amount of cellular uptake. 19 Because NSC was prepared using the same method as that of PSC, the high fluorescence observed for NSC is consistent with the results obtained previously.…”

“…As a reference, the viability of Caco-2 cells treated with PTX solution for 72 hours was 71.45. 19 The inhibition efficiency of PS and PSC containing 5 µM and 10 µM PTX increased upon increasing the incubation time from 24 hours to 48 hours. The cell viability after treatment with PSC significantly decreased upon increasing the incubation time up to 72 hours at both PTX concentrations.…”

“…The resultant SLNs had improved in vitro cytotoxicity 19 and oral bioavailability. 20 Herein, we aimed to decrease the burst release of PTX, reduce its renal toxicity, prolong its anticancer activity, and enhance its absorption.…”

“…19 Briefly, 100 mg stearic acid was melted at 80°C in a water bath. PTX (5 mg) was dissolved in ethanol (0.25 mL) by vortexing, and the solution was warmed to 80°C in a water bath.…”

Effect of integrin receptor-targeted liposomal paclitaxel for hepatocellular carcinoma targeting and therapy

“…However, various reports have indicated that Cremophor EL may induce a number of serious side effects, including acute neurotoxicity, hypersensitivity, cardio toxicity and nephrotoxicity (11). Recently, an albumin-bound PTX nanoparticle (Abraxane™) became the first Cremophor EL-free PTX agent approved for the treatment of various types of cancer, including lung, breast and pancreatic cancer, by the Food and Drug Administration (Silver Spring, MA, USA) (5,9). The application of this agent in cancer treatment may reduce the toxicities associated with PTX-based therapy and increase the loading efficiency of PTX to >85% [1:9 (w/w) PTX and albumin mixture].…”