Biodegradable preparation, characterization and In vitro evaluation of stealth docetaxel lipid nanoemulsions for efficient cytotoxicity
Keywords:
Docetaxel, DSPE-PEG 5000, DPPE-PEG 5000, Stealth Lipid Nanoemulsions, cytotoxicityAbstract
Docetaxel is currently used in treatment of breast and ovarian cancers, administered in the form of parenteral IV infusion. Lipid nanoemulsion (LNE) delivery system is biocompatible, biodegradable and easy to prepare. The aim of this study was to develop stable parenteral pegylated docetaxel lipid nanoemulsions (LNEs) for improving cytotoxicity. The O/W LNEs were prepared by homogenization and ultrasonication process. The globule sizes and zeta potentials were measured by using Malvern Zetasizer. The sizes of oil globules varied from 70.2 to 243.3 nm and zeta potential from î25.5 to î40.2mV. During in vitro drug release studies, the cumulative percentage drug released within 15 h from pegylated lipid nanoemulsions, PLNE-3 and PLNE-6 was 84.02μ4.79 and 88.51μ4.5 respectively. The total drug content and entrapment efficiencies for the prepared LNEs were determined by HPLC. The in vitro cell line studies were performed on two cell lines (MCF-7 and Hela cell lines). When compared to drug solution, PLNE-6 was found to have 1.55 and 1.6 folds more cytotoxic activity on MCF-7 and Hela cell lines respectively. The IC 50 values of pegylated LNEs on both the cell lines was statistically significant when compared to DS, P<0.05. In conclusion, stealth LNEs were prepared, characterized and found to be stable and superior in delivery of docetaxel to cancer cell lines in comparison to plain LNE and drug solution.
References
. Ringel I, Horwitz SB. A semisynthetic
analogue of Taxol. J Natl Cancer Inst
: 83: 288-91.
. Diaz JF, Andreu JM. Assembly of
purified GDP-tubulin into microtubules
induced by Taxol and Taxotere:
reversibility, ligand stoichiometry, and
competition. Biochemistry 1993: 32:
-55.
. Kintzel PE, Michaud LB, Lange MK.
Docetaxel-associated epiphora.
Pharmacotherapy 2006: 26: 853-67.
. Jain RK, Stylianopoulos T. Delivering
nanomedicine to solid tumors, Nat.
Rev.Clin. Oncol. 2010: 7: 653ă664.
. Matsumura Y, Maeda H. A new concept
for macromolecular therapeutics in
cancer chemotherapy: mechanism of
tumoritropic accumulation of proteins
and the antitumor agent smancs, Cancer
Res. 1986: 46: 6387ă92.
. Gabizon A, Shmeeda H, Zalipsky S.
Pros and cons of the liposome platform
in cancer drug targeting. J. Liposome
Res. 2006: 16: 175ă183.
. Moghimi SM, Patel HM. Serummediated recognition of liposomes by
phagocytic cells of the reticulo
endothelial system ă the concept of
tissue specificity. Adv. Drug Deliv. Rev.
: 32: 45ă60.
. Gabizon A, Papahadjopoulos D.
Liposome formulations with prolonged
circulation time in blood and enhanced
uptake by tumors. Proc. Natl. Acad. Sci.
U.S.A. 1988: 85: 6949ă6953.
. Ishida O, Maruyama K, Sasaki K,
Iwatsuru M. Size-dependent
extravasation and interstitial localization
of polyethylene glycol liposomes in solid
tumor-bearing mice. Int. J. Pharm. 1999:
: 49ă56.
. Lundberg BB, Mortimer BC, Redgrave
TG. Submicron lipid emulsions
containing amphipathic polyethylene
glycol for use as drug-carriers with
prolonged circulation time. Int. J.
Pharmaceutics. 1996: 134: 119-127.
. Lundberg B. A submicron lipid emulsion
coated with amphipathic polyethylene
glycol for parenteral administration of
paclitaxel (taxol). J. Pharm.Pharmacol.
: 49: 16ă21.Bareford LM, Swaan
PW. Endocytic mechanisms for targeted
drug delivery. Adv Drug Deliv Rev
:59(8):748-58.
. Lundberg BB. Preparation of drugcarrier emulsions stabilized with
phosphatidyl choline- surfactant
mixtures. J. Pharm. Sci. 1994: 83: 72-
. Patlolla RR, Vobalaboina V.
Pharmacokinetics and tissue distribution
of Etoposide delivered in parenteral
emulsion. J. Pharm. Sci. 2005: 94 (2):
ă 445.
. Harris JM, Chess RB. Effect of
pegylation on pharmaceuticals. Nat.
Rev. Drug Discov. 2003: 2: 214î221.
. Veronese FM, Pasut G. PEGylation,
successful approach to drug delivery.
Drug Discov Today. 2005:10: 1451î58.
. Kun Gao, Jin Sun, Kai Liu, Xiaohong
Liu, Zhonggui He. Preparation &
Characterization of a Submicron Lipid
Emulsion of Docetaxel: Submicron Lipid
Emulsion of Docetaxel. Drug Dev Ind
Pharm. 2008: 34:1227ă37.
. Ciccolini J, Catalin J, Blachon MF,
Durand A. Rapid high-performance
liquid chromatographic determination of
docetaxel (Taxotere) in plasma using
liquid-liquid extraction . J Chromatogr B
Biomed Sci Appl. 2001: 759: 299-306.
. Prabhakar K, Muzammil Afzal Sd,
Surendar G, Kishan V. Brain specific
delivery of pegylated indinavir submicron
lipid emulsions. Eur. J. Pharm. sci. 2011:
: 423ă432.
. Buszello K, Harnisch S, Müller RH,
Müller BW. The influence of alkali fatty
acids on the properties and the stability
of parenteral O/W emulsions modified
with Solutol HS15®. Eur. J. Pharm.
Biopharm. 2000: 49 (2): 143ă149.
. Krishna G, Wood GC, Sheth BB.
Improving emulsification efficacy of
lecithin by formulation design. I. Effect of
adding secondary surfactant. PDA J.
Pharm. Sci. Technol. 1998: 52: 331-336.
. Shotton E, Davis SS. A note on the
stability of emulsion on high dilution. J.
Pharm Pharmacol. 1968: 20(11): 825-
. Washington C, Chawla A, Christy N,
Davis SS. The electrokinetic properties
of phospholipid stabilized fat emulsions.
Int. J. Pharmaceut. 1989:54: 191-197.
. Duncan R, Kopecek J, Lloyd JB. Drug
targeting to lysosomes. Biochem Soc
Trans 1984: 12(6):913-5.
. Groves MJ, Herman CJ. The
redistribution of bulk aqueous phase
phospholipids during thermal stressing
of phospholipid-stabilized emulsions, J
Pharm Pharmacol. 1993: 45: 592-596.
. Joanna R, Suzanne G, Khalid MD N,
Pascal D, Allen C, Leroux JC. Longcirculating poly (ethylene glycol)-coated
emulsions to target solid tumors. Eur. J.
Pharm Biopharm. 2007: 67: 329ă338.
. Meyer S, Berrut S, Goodenough TIJ,
Rajendram VS, Pinfield VJ, Povey MJW.
A comparative study of ultrasound and
laser light diffraction techniques for
particle size determination in dairy
beverages. Meas. Sci. Technol. 2006:
: 289-297.
. Papahadjopoulos D, Allen TM, Gabizon
A, Matthay K, Huang SK, Lee KD,
Woodle MC, Lasic DD, Redemann C.
Sterically stabilized liposomes:
Improvements in pharmacokinetics and
antitumor therapeutic efficacy. Proc Natl
Acad Sci., USA 1991: 24: 11460ă11464.
. Senior J, Delgado C, Fisher D, Tilcock
C, Gregoriadis, G. Influence of surface
hydrophilicty of liposomes on their
interaction with plasma protein and
clearance from the circulation: Studies
with poly (ethylene glycol) coated
vesicles. Biochim Biophys Acta 1991:
: 77ă82.
