Formulation of LDL Targeted Nanostructured Lipid Carriers Loaded with Paclitaxel: A Detailed Study of Preparation, Freeze Drying Condition, and In Vitro Cytotoxicity

Abstract

In the present study, cholesterol nanostructured lipid carriers with various oleic acid content loaded with paclitaxel (PTX) were prepared by solvent emulsification-diffusion method using a Taguchi design. Size, zeta potential, entrapment efficiency, drug loading, and release percent of NLCs were measured. The results indicated that the most effective factors on the size were oleic acid content and surfactant percent. Zeta potential was more affected by the drug content. Drug to-lipid weight ratio was the most effective factor on entrapment efficiency and drug release from NLC. In the present work, the effect of lyophilization on the particle size and release properties of NLCs was also evaluated. The results revealed no differences between the characteristics of NLCs before and after freeze drying by using 25% w/w sorbitol as cryoprotectant. Cytotoxicity studies indicate that PTX associated with the NLC is also effective in HT-29 cell lines and enters the cancer cells selectively through the LDL receptor endocytic pathway. The IC 50 values of free PTX solubilized in Cremophor EL and NLC-born PTX after 72 h exposure were 8.32 ± 1.35 ng/mL and 5.24 ± 0.96 ng/mL, respectively.

In vivopharmacokinetics, biodistribution and anti-tumor effect of paclitaxel-loaded targeted chitosan-based polymeric micelle

“…Untreated cells were taken as the negative control with 100% viability and the blank culture medium was used as a blank control. Cell viability for DOI: 10.3109/10717544.2014.954281 each sample was calculated using following equation (Emami et al, 2012 Folate competition assays 4T1 cells were exposed to a constant drug concentration of 1.17 mM, while being maintained in growth media supplemented with free folate molecules within the concentration rang of 0-500 mg/L. The viabilities of the cells were then quantified, as described above.…”

“…administration (Kim et al, 2001). Application of Taxol Õ is also limited by its short-term physical stability since PTX tends to precipitate out of the aqueous media upon dilution (Emami et al, 2012). Hence, many attempts have been devoted to substitute the Cremophor Õ EL-based formulation with alternative carriers which enable delivering PTX selectively to the tumor tissues with significantly reduced adverse effects on normal cells.…”

Preparation of Fe3O4/Reduced Graphene Oxide Nanocomposites with Good Dispersibility for Delivery of Paclitaxel

“…For improving the bioavailability of PTX, some groups made different carriers to load PTX such as hydrogels [2,3], gel system [4], implantable chitosan film [5], nanogel [6], nanoparticles [7,8], and nanostructured lipid carrier [9].…”

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

“…33,34 Alternatively, LDL-mimicking nanocarriers without protein, including lipid nanoparticles and Emuls, have emerged as promising candidates for the targeted delivery of antineoplastic drugs. 17,21,33,35,36 In our previous study, a novel lipid Emul resembling the structure of LDL, which is composed of a PTX-CH complex surrounded by a phospholipid monolayer, was prepared and the in vitro and in vivo antitumor efficacy evaluated in a TNBC model. 26,27 The resulting lipid PTX-CH Emul exhibited superior in vitro antitumor efficacy, higher specificity …”