FORMULATION AND EVALUATION OF DOCETAXEL TRIHYDRATE LOADED SELF-ASSEMBLED NANOCARRIERS FOR TREATMENT OF HER2 POSITIVE BREAST CANCER

Nilesh Ramesh Rarokar, Pramod Bhujangrao Khedekar

Abstract


Human Epidermal Growth Factor Receptor 2-positive (HER2-positive) breast cancer tend to be more aggressive among all breast cancers. Breast cancers with HER2 gene amplification or HER2 protein overexpression are called HER2-positive. It tends to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers. HER2 positive breast cancer is often treated with chemotherapy drugs called anthracylines (e.g. doxorubicine, epirubicine), taxanes (e.g. Docetaxel, peclitaxel) as well as some others, usually in combination of two or more chemotherapy drugs1 but the development of potential drug delivery system by using nanotechnology is also the important aspect for the proper treatment of HER2 positive breast cancer. The aim of this study was to develop DTX-loaded self assembled nanocarriers (SANs) for treatment of HER2 positive breast cancer and also to evaluate their efficacy to release the drug by controlled manner. SANs were prepared from a glyceryl monooleate, Pluronic® F127 (0.5 – 1.5 % w/v) and Pluronic® F68 (0.25-1.0 %w/v) in different concentration with or without docetaxel trihydrate (DTX) (2.0%w/v) by high pressure homogenization, before preparation compatibility of drug and polymers was studied by differential scanning calorimetry (DSC) and FTIR spectroscopy. Prepared SANs was then subject to different evaluation test particle size, zeta potential, % entrapment efficiency, drug content, in vitro drug release study, measurement of pH, and stability study. Particle size of SANs prepared with Pluronic® F127 was found in the range of 170 nm to 280 nm whereas SANs with Pluronic® F68 was found between 200 to 240 nm and it shows more negative zeta potential value than -30 mV. More than 90 % of DTX was found to be entrapped in SANs formulations loaded with DTX 2.0% w/v. Drug released study revealed that formulation F9 containing 0.25% PF68 shows 89.59 % release after 12 h and F5 containing 1.0% PF127 releases 96.56% drug after 12 h. Results of one month stability study shows that the SANs formulations were found to be stable over a one month. Hence, the DTX-loaded SANs was act as an potential drug carrier to fulfill the demand of cancer therapeutics.


References


Sevcikova K, Vertakova-Krakovska B, Spanik S, Neoadjuvant Treatment in Patients with HER2-Positive Breast Cancer. ISRN Oncology, 2013; 1-8.

Rizwan SB, Boyd BJ, Rades T, Hook S, Bicontinuous cubic liquid crystals as sustained delivery systems for peptides and proteins, Expert Opinion on Drug Delivery, 2010; 7(10):1133-1144

Bei D, Marszalek J, Youan BC, Formulation of Dacarbazine Loaded Cubosomes—Part I: Influence of Formulation Variables, AAPS Pharm Sci Tech. 2009; 10(3):1032-1039.

Fontell, K., Mandell, L., and Ekwall, P., "Isotropic Mesophases in Systems Containing Amphiphilic Compounds," Acta Chem. Scand. 1968; 22:3209-23.

Shah JC, Sadhale Y, Chilukuri DM, Cubic phase gels as drug delivery systems, Adv Drug Deliver Rev. 2001; 47:229–250.

Burrows R, Collett JH, Attwood D, The release of drugs from monoglyceride-water liquid crystalline phases, Int. J. Pharm. 1994; 111:283-293.

Drummond CJ, Fong C, Surfactant self assembly objects as novel drug delivery vehicles, Current Openion Colloid Interface Science (2000) 449-456.

Barauskas J, Johnsson M, Joabsson F, Tiberg F. Cubic phase nanoparticles (cubosome): principles for controlling size, structure, and stability. Langmuir 2005; 21(6):2569–77.

Barauskas J, Johnsson M, Tiberg F. Self-assembled lipid superstructures: beyond vesicles and liposomes. Nano Lett. 2000; 5(8):1615–19.

Rarokar NR, Saoji SD, Raut NA, Taksande JB, Khedekar PB, Dave VS. Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative Approach for the Controlled Delivery of Docetaxel. AAPS PharmSciTech. 2015; 17:436-445.

Fong W, Hanley T, Boyd B, Stimuli responsive liquid crystals provide ‘on-demand’ drug delivery in vitro and in vivo, J. Control. Release. 2009; 135:218-226.

Dong YD, Larson I, Hanley T, Boyd BJ, Bulk and dispersed aqueous phase behaviour of phytantriol: effect of vitamin E acetate and F127 polymer on liquid crystal nanostructure, Langmuir, 2006; 22:9512-9518.

Luzzati V, Tardieu A, Gulik-Kryzwicki T, Rivas E, Riess-Husson F, Nature (London) 1968; 220:485-487.

Gaikwad V, et al. Formulation and evaluation of In-Situ gel of metoprolol tartrate for nasal delivery. J Pharm Res. 2010; 3:788-793.

Maghsoudi A, Shojaosadati SA, Vasheghani Farahani E. 5hFluorouracil-loaded BSA nanoparticles: formulation optimization and in-vitro release study. AAPS Pharm Sci Tech. 2008; 9(4):1092–6.


Full Text: PDF

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

footer_848
ISSN: 2250-1177  This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.