Raloxifene/SBE-β-CD Inclusion Complexes Formulated into Nanoparticles with Chitosan to Overcome the Absorption Barrier for Bioavailability Enhancement

Abstract

Raloxifene (RXF) is a hormone-like medication used for treating postmenopausal osteoporosis and estrogen-dependent breast cancer, yet associated with bad low bioavailability due to poor solubility. This study was intended to develop cyclodextrin/chitosan nanoparticles (ccNPs) for oral delivery of RXF in order to enhance the oral bioavailability. RXF-loaded ccNPs (RXF-ccNPs) were prepared by cyclodextrin inclusion followed by complexation with chitosan. RXF-ccNPs were fully characterized by particle size, morphology and in vitro drug release. The oral delivery efficacy and transepithelial transport potential were evaluated by pharmacokinetics, in situ single-pass intestinal perfusion, cellular uptake and ex vivo imaging. The resulting RXF-ccNPs were around 165 nm in particle size with a narrow distribution. The oral bioavailability of RXF was enhanced by 2.6 folds through ccNPs compared to RXF suspensions in rats. It was shown that RXF-ccNPs could improve the intestinal permeability of RXF, increase the cellular uptake of RXF and facilitate its transport across the absorptive epithelia. The results indicate that our developed ccNPs based on sulfobutylether-β-cyclodextrin and oligochitosan are a promising vehicle to orally deliver poorly water-soluble drugs over and above RXF.

RETRACTED: Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment

“…RLX has been reported to stimulate gene promoters regulated by ERβ subtype that guards against tumor formation in response to estrogen; therefore, it exhibits anti-tumor activity in breast cancer cells [ 6 ]. Nevertheless, RLX suffers from poor aqueous solubility and exposure to dramatic pre-systemic metabolism that lead to diminished bioavailability that does not surpass 2% [ 7 , 8 ].…”

Green Nanotechnology in the Formulation of a Novel Solid Dispersed Multilayered Core-Sheath Raloxifene-Loaded Nanofibrous Buccal Film; In Vitro and In Vivo Characterization

“…For the purpose of enhancing RLX bioavailability, Wang et al [ 84 ] reported the formulation of RLX inclusion complex using sulfo-butyl-ether-β-cyclodextrin followed by conjugation to chitosan to form RLX-loaded cyclodextrin/chitosan nanoparticles (RLX-ccNPs). The enhancement of oral bioavailability of RLX-ccNPs relative to RLX suspensions was about 3.60-fold.…”

Combined Approach of Cyclodextrin Complexationand Nanostructured Lipid Carriers for the Development of a Pediatric Liquid Oral Dosage Form of Hydrochlorothiazide

“…The effectiveness of simultaneously exploiting the advantages of both CD and nano-lipid carriers by joining them in a unique drug delivery system, by loading the drug-CD system into the lipid nanoparticles, has recently been reported [32,33,34,35]. In particular, loading into SLN of HCT as HPβCD binary system rather than as plain drug allowed to enhance the entrapment efficiency from 57% up to 66%, to prolong the formulation stability at 4 °C from 1 to 3 months, and to improve the drug release, with an almost 3-times increase of the released amount after 6 h [21].…”