Nanolipid carrier-based thermoreversible gel for localized delivery of docetaxel to breast cancer

Abstract

Intratumoral and intralesional administration of anticancer drugs in gels and implantable formulations is gaining much importance on account of its advantage of site-specific delivery with highly dependable freedom from unwanted side effects. Nanolipid carriers (NLC) are the preferred vehicle due to their improved properties particularly drug loading. In the present investigation, glyceryl monostearate–oleic acid NLCs loaded with docetaxel were prepared by emulsification and ultrasonication technique and were incorporated in thermoreversible pluronic F127 gel (TRPgel) for intralesion injection to breast tissue. The NLCs were spherical particles of 113 nm size with a negative zeta potential of −32.8 and 85 % drug entrapment. In vitro drug release profile of the NLC showed 96 % drug release in 48 h following Higuchi release kinetics. NLC incorporated TRPgel showed mucoadhesive force of 3.07 dynes/cm2 and gelling temperature in the range of 32 to 37 °C. The drug entrapped gel was also subjected to in vitro cytotoxicity study in human B-16 and HeLa cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo drug distribution study in breast tissue in healthy Wistar rats. The MTT assay revealed that docetaxel-loaded NLC incorporated into gel showed lower cytotoxicity than docetaxel. However, in vivo breast tissue distribution studies showed high tissue drug concentration, sustained over a period of 60 h in comparison to docetaxel and docetaxel-loaded NLCs. These results suggest that nanolipid carrier of docetaxel in TRPgel could be a promising carrier system to deliver drug to tumor by intralesional administration for improving therapeutic benefits of docetaxel.

Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma

“…Encapsulation into NLC DTX and HGel-NLC DTX determined significant (p < 0.05) reduction in the toxicity of DTX against all evaluated cell lines, within 24 h of treatment, as shown by the increased IC 50 values (Table 2). Similar changes in cytotoxic response were observed by other authors that used lipid nanocarriers for DTX delivery [11,57] or a thermoreversible gel containing adsorbed NLC DTX for the treatment of breast cancer [58]. In all cases, the authors attributed the decrease in cytotoxicity (regarding DTX T-HYD ) to the sustained release of docetaxel from such hybrid systems, which also explains the increase in cytotoxicity registered after 72 h of treatment (Figure S4).…”

Development and characterization of arteether-loaded nanostructured lipid carriers for the treatment of malaria

“…Th e prepared emulsion was then sonicated for 2 min for further reduction in size. Finally, the formulation was refrigerated at 2 ° C -5 ° C for 15 -20 min (Vohra et al 2013). …”

Self‐Assembled Antimitotic Peptide Vesicle Designed fromα,β‐Tubulin Heterodimer Interface for Anticancer Drug Delivery

“…Nevertheless, higher toxicity at its effective dose as well as numerous side effects limited their combined application [15] . In this context it is quite important to achieve a low but steady concentrations of microtubule‐targeted drugs in the vicinity of tumour micro‐environment for long durations as compare to sharply rising and falling drug concentrations, which will have deleterious effect on healthy cells [16–19] . Peptide based therapeutics emerge as prominent and quite successful modulator of tubulin dynamics through achieving facile protein‐peptide interaction [20–22] .…”

“…[15] In this context it is quite important to achieve a low but steady concentrations of microtubule-targeted drugs in the vicinity of tumour micro-environment for long durations as compare to sharply rising and falling drug concentrations, which will have deleterious effect on healthy cells. [16][17][18][19] Peptide based therapeutics emerge as prominent and quite successful modulator of tubulin dynamics through achieving facile protein-peptide interaction. [20][21][22] Comparatively low toxicity and more selectivity renders them a successful candidature towards the development of new anticancer drug.…”