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ORIGINAL/BRIEF
Year : 2012  |  Volume : 4  |  Issue : 5  |  Page : 17-18  

Design and characterization of anionic PEGylated liposomal formulation loaded with paclitax for ovarian cancer


Department of Pharmacy, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, Gujarat, India

Date of Web Publication21-Mar-2012

Correspondence Address:
K Makwana
Department of Pharmacy, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-7406.94122

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   Abstract 

Despite its strong antitumor activity, paclitaxel (Taxol® ) has limited clinical applications due to its low aqueous solubility and hypersensitivity caused by cremophor EL and ethanol which is the vehicle used in the current commercial product. In an attempt to develop a pharmaceutically acceptable formulation that could replace Taxol® , we have prepared PEGylated liposomes containing paclitaxel to improve its solubility and physicochemical stability. Its percent drug entrapment (PDE), mean particle size, zeta potential and in vitro release profile were determined. The optimized PEGylated liposomes provided high percent entrapment efficiency (64.29%) and mean particle size of 228.6 nm. The electroflocculation method showed 5 mol% of DSPE-mPEG2000 was required to obtain maximum stability for PEGylated liposome. In vitro release data showed its long circulating characteristic. Paclitaxel loaded PEGylated liposomes can be considered a promising long circulating paclitaxel delivery with absence of side effects related to Taxol® .

Keywords: Antitumor activity, electroflocculation, in vitro release, thin film hydration


How to cite this article:
Makwana K, Tandel H. Design and characterization of anionic PEGylated liposomal formulation loaded with paclitax for ovarian cancer. J Pharm Bioall Sci 2012;4, Suppl S1:17-8

How to cite this URL:
Makwana K, Tandel H. Design and characterization of anionic PEGylated liposomal formulation loaded with paclitax for ovarian cancer. J Pharm Bioall Sci [serial online] 2012 [cited 2020 Aug 9];4, Suppl S1:17-8. Available from: http://www.jpbsonline.org/text.asp?2012/4/5/17/94122

Paclitaxel (PTX) is one of the most useful anticancer agent which has been used for various cancers including primary epithelial ovarian carcinoma, breast cancer, head and neck cancers and non-small cell lung cancer. Paclitaxel is indicated as monotherapy for the treatment of metastatic ovarian cancer where standard platinum-based therapy fails. Paclitaxel is a hydrophobic molecule and poorly soluble in water, for which reason it is solubilized in a 50:50 mixture of cremophor el (polyethoxylated castor oil) and ethanol but cremophor has been associated with number of side effects, including hypersensitivity, nephrotoxicity, neurotoxicity. It also dissolves phthalate plastics from commonly-used PVC bags and intravenous infusion line. The use of cremophor as a vehicle also appears to alter the biochemical properties of lipoproteins, such as HDL. to overcome these problems, new aqueous-based formulation of paclitaxel that do not require solubilisation by cremophor, is currently being developed. One of this aqueous based formulation is liposomes. liposomes are biologically inert, free from antigenic, pyrogenic and allergic reactions. Liposomal preparations are expected to be accumulated preferentially in many types of solid tumors due to the enhanced permeability and retention (EPR) effect, because solid tumors possess unique pathophysiological characteristics that are not observed in normal tissues, such as extensive angiogenesis, defective vascular architecture and impaired lymphatic drainage.


   Materials and Methods Top


Material

Paclitaxel obtained as gift sample from SUN pharmaceuticals, HSPC (Hydrogenated soya phosphatidyl choline), DPPG (1,2-Dipalmitoyl-sn-glycero-3-phospho-rac-glycerol), Cholesterol, mPEG-DSPE (N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine), All lipids were provided by lipoid (Germany).

Methods

Liposomal formulation of paclitaxel was prepared by Thin film hydration method and optimized based on following evaluation parameters: (1) Percent Drug Entrapment: Analysis method was RP-HPLC with UV as detector at 229nm. (2) Zeta potential: Using malvern zeta sizer. (3) Mean particle size: Using malvern zeta sizer. PEGylated liposomes were prepared by Pre-insertion technique and amount of mPEG-DSPE was optimized based on 'sodium sulphate induced flocculation test'. Prepared optimized formulation was evaluated by different parameters. It includes zeta potential, mean particle size, in vitro release study.


   Results and Discussions Top


Sodium sulphate induced flocculation test is to evaluate formulation for protection provided by PEGylation against salts present in blood plasma. Normal Sodium (Na) level in blood plasma is 135-145 mM/L (i.e. 0.135M to 0.145M), that can be correlated to 0.2 M concentration of sodium sulphate used. Study demonstrated that 5 mol% mPEG-DSPE concentration prevents liposomes maximum from flocculation at 0.2 M concentration of electrolyte (data not shown). Zeta potential of prepared formulation was found to be -21.2 mV. Mean particle size was found to be 228.6 nm with PDI 0.193. In vitro release study showed 16% drug release within 48 hrs that showed its prolonged release in release media [Table 1], [Figure 1].
Figure 1: In vitro release study

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Table 1: Evaluation parameters

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   Conclusion Top


In present investigation, an attempt was made to overcome the problems associated with vehicle used in marketed formulation of paclitaxel (Taxol® ) by developing novel aqueous based liposomal formulation which was found to be stable and long circulating. Negative zeta potential showed stability against aggregation. Mean particle size of 228.6 nm and PEGylation will escape RES uptake and allow to accumulate preferentially in ovarian cancer cells. In vitro release study showed it to be having prolonged release. So, it can be concluded that the prepared formulation would avoid lethal systemic toxicities of paclitaxel by targeting to the tumor and also avoid toxicities related to vehicle, cremophor EL. [1],[2]

 
   References Top

1.Crosasso P, Ceruti M, Brusa P, Arpicco S, Dosio F, Cattel L. Preparation, characterization and properties of sterically stabilized paclitaxel-containing liposomes. J Control Release 2000;63:19-30.  Back to cited text no. 1
    
2.Yang T, Cui FD, Choi MK, Cho JW, Chung SJ, Shim CK, et al. Enhanced solubility and stability of PEGylated liposomal paclitaxel: In vitro and in vivo evaluation. Int J Pharm 2007;338:317-26.  Back to cited text no. 2
    


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