Self-Assembled Nanomicellar Formulation of Docetaxel as a Potential Breast Cancer Chemotherapeutic System

Abstract

Docetaxel (DTX) is classified as a class IV drug that exhibits poor aqueous solubility (6–7 µg/mL in water) and permeability (P-glycoprotein substrate). The main objective of this study was to construct, characterize, and evaluate docetaxel loaded nanomicellar formulation in vitro for oral delivery to enhance the absorption and bioavailability of DTX, as well as to circumvent P-gp efflux inhibition. Formulations were prepared with two polymeric surfactants, hydrogenated castor oil-40 (HCO-40) and D-α-Tocopherol polyethylene glycol 1000 succinate (VIT E TPGS) with solvent evaporation technique, and the resulting DTX nanomicellar formulations were characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier Transform Infrared Spectroscopy (FT–IR), X-ray powder diffraction (XRD), and transmission electron microscopy (TEM). Proton NMR, FT–IR, and XRD data indicated that DTX was completely encapsulated within the hydrophobic core of the nanomicelles in its amorphous state. TEM data revealed a smooth spherical shape of the nanomicellar formulation. The optimized formulation (F-2) possessed a mean diameter of 13.42 nm, a zeta potential of −0.19 mV, with a 99.3% entrapment efficiency. Dilution stability study indicated that nanomicelles were stable up to 100-fold dilution with minimal change in size, poly dispersity index (PDI), and zeta potential. In vitro cytotoxicity study revealed higher anticancer activity of DTX nanomicelles at 5 µM compared to the native drug against breast cancer cell line (MCF-7) cells. The LC–MS data confirmed the chemical stability of DTX within the nanomicelles. In vitro drug release study demonstrated faster dissolution of DTX from the nanomicelles compared to the naked drug. Our experimental results exhibit that nanomicelles could be a drug delivery system of choice to encapsulate drugs with low aqueous solubility and permeability that can preserve the stability of the active constituents to provide anticancer activity.

Co-Delivery of siRNA and Docetaxel to Cancer Cells by NLC for Therapy

“…DTX, DTX-loaded NLCs, and empty NLCs were dissolved in deuterated DMSO (DMSO- d 6 ) for NMR ( 1 H NMR) analysis in the formulations. Analyses of the samples were performed by using an NMR (Bruker 500 MHz UltraShield NMR, Germany) device …”

“…Analyses of the samples were performed by using an NMR (Bruker 500 MHz UltraShield NMR, Germany) device. 12 …”

Ternary inclusion complex of docetaxel using ß-cyclodextrin and hydrophilic polymer: Physicochemical characterization and in-vitro anticancer activity

“…Afterward, the suspension in vials was withdrawn and filtered (0.22 μm pores size). The filtrate was then analyzed by UV-Visible spectroscopy (Schimadzu, UV-1800) at 230 nm for estimation of DOCE content (Alshamrani et al, 2022). A phase solubility diagram was then plotted between β-CD concentration and DOCE concentration and the values of stability constant (K s ) and complexation efficiency (CE) were calculated from obtained curve using Equation ( 1) and (2).…”

“…The FTIR spectrum of β-CD revealed the vibration of free -OH groups between 3,300 and 3,500 cm −1 and for -CH stretching at 2,926.23 cm −1 . Docetaxel showed characteristic IR absorption peaks at 3,369, 2,982, 1,717, 1,437, 1,241, and 707 cm −1 attributed to -OH, -CH asymmetric stretch, C=O stretch, C=C stretch, C-O stretch, and C-H bend, respectively (Lim et al, 2015;Alshamrani et al, 2022). The peaks corresponding to C=C and C-O stretching vibrations were absent in the binary complex, DOCE-β-CD-BC, emphasizing the complexation of N-tert-butyl group of DOCE in β-CD cavity.…”

“…A number of approaches have been utilized to enhance aqueous solubility of docetaxel such as liposomes, PEGylated liposomes, polymeric, metallic, and hybrid nanoparticles, selfemulsifying formulations, self-assembled nanomicells, dendrimers, etc. However, all these formulations have a limitation in terms of cost, stability, and scale-up (Alshamrani et al, 2022;Campani et al, 2022;Muhammad et al, 2018;Vakili-Ghartavol et al, 2020;Zawilska et al, 2021). Therefore, a well-established, complexation technique with cyclodextrin for solubility enhancement of docetaxel is chosen for the present work.…”