FORMULATION, DEVELOPMENT AND CHARACTERIZATION OF SOLID LIPID NANOPARTICLES OF GEMCITABINE HYDROCHLORIDE
Gemcitabine Hydrochloride is a BCS class III drug of choice in the treatment of cancer, as a single or in combination chemotherapy. However, its bioavailability is a major concern due to its short half-life. Solid lipid nanoparticles (SLN) of Gemcitabine Hydrochloride were prepared to enhance its bioavailability, hence anticancer activity. The Quality by Design approach was applied for theÂ formulation of SLN. The Randomized 32 factorial design was used with responses of particle size and % entrapment efficiency (% EE). The optimized batch of Gemcitabine Hydrochloride loaded SLN containing 1gm of GMS as solid lipid, 1gm of Tween80: Sodium Taurocholate as surfactant:co-surfactant and 5mg of Gemcitabine Hydrochloride was prepared by high shear homogenization method followed by Probe sonication for 15min to form nanoparticulate SLN dispersion. TheÂ Optimized batch of Gemcitabine Hydrochloride loaded SLN that exhausted mean particle size of 126.1nm, zeta potential -28.6 mV and % EE 74.83% respectively. SEM studies revealed three-dimensional nature of SLN with aÂ slightly rough surface. DSC, results exhibited entrapment of Gemcitabine Hydrochloride in SLN. The optimized batch of SLN was evaluated for in-vitro % drug release using cellulose membrane dialysis bags for 24hrs and showed 63.13% CDR at 24 hrs. Anticancer cell line studies were also performed in human lung cancer cell line (A-549). It concludes that Gemcitabine Hydrochloride loaded Solid lipid Nanoparticles was successfully formulated and evaluated to sustain the drug release by bypassing the first pass metabolism.
Key words: Gemcitabine Hydrochloride, SLN, QbD, High shear homogenization, anticancer activity.
2. Abratt RP. Gemcitabine Hydrochloride: Combination of activity and tolerability. Anticancer Drugs, 1995; 6:63-64.
3. Manjunath K, Reddy JS, Venkateswarlu V., Solid lipid nanoparticles as drug delivery systems, Methods Find. Exp. Clin. Pharmacol. 2005; 27:127-144.
4. MÃ¼ller RH, Mehnert W, Lucks JS, Schwarz C, Zur MÃ¼hlen A, Weyhers H, Freitas C, RÃ¼hl D, Solid lipid nanoparticles (SLN) - An alternative colloidal carrier system for controlled drug delivery, Eur. J. Pharm. 1995; 41:62-69.
5. Gohla S, Rainer H, MuÃˆller, Karsten MaÃˆder, Solid lipid nanoparticles (SLN) for controlled drug delivery - A review of the state of art. Eur. J. Pharm. Biopharm. 2000; 50:161-177.
6. Lawrence TS. Radiation sensitizers and targeted therapies, oncology. 2003; 17:23-28.
7. Mokashi AS, Solid lipid nanoparticles of gemcitabine hydrochloride. bentham science publishers 2012; 2:0000-0000.
8. Siekmann B, Westesen K. Investigations on solid lipid nanoparticles prepared by precipitation in o/w emulsions. Eur. J. Pharm. Biopharm.(1996; 43:104-109.
9. Reddy LH. Couvreur, P.Novel Approaches to deliver gemticabine to cancers. Curr.Pharm. Des., 2008; 14:1124-1137.
10. Lionberger RA, Lee LS, Lee L, Raw A ,Yu LX, Quality by design: Concepts for ANDAs, The AAPS Journal, 2008; 10:268â€“276.
11. Nadpara NP, Quality By Design (QBD): A complete Review. Int.J.pharm.sci.Rev.Res. 2012; 17(2):04, 20-28.
12. Skehn P, Storeng R, Scudiero A, Monks J, McMohan D, Vistica D, Jonathan TW, Bokesch H, Kenney S, Boyd M R. New colorimetric cytotoxicity assay for anticancer drug screening J. Natl. Cancer Inst. 1990; 82:1107.
13. Vichai V, Kanyawim K. Sulforhodamine B colorimetric assay for cytotoxicity screening Nature Protocols. 2006; 1:1112-1116.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).