140
M.G. Sarpietro et al. / International Journal of Pharmaceutics 436 (2012) 135–140
4. Conclusion
Jackson, J.K., Hung, T., Letchford, K., Burt, H.M., 2007. The characterization of
paclitaxel-loaded microspheres manufactured from blends of poly(lactic-co-
glycolic acid) (PLGA) and low molecular weight diblock copolymers. Int. J. Pharm.
342, 6–17.
Starting from the evidence that only a small amount of pacli-
taxel can be incorporated into liposomes, we conjugated the drug
to 1,1ꢀ,2-trisnorsqualenoic acid with the aim to obtain a molecule
with a stronger affinity with the phospholipid bilayers and that can,
consequently, be incorporated and retained in the lipid system. The
results obtained clearly indicate an improved incorporation effi-
ciency of squalenoyl–paclitaxel with respect to paclitaxel into the
liposome, probably due to its stronger lipophilic character. In addi-
tion, liposome can retain the incorporated squalenoyl–paclitaxel
and hence a lipid system could be considered as a possible carrier
for the prodrug.
Kanehisa, M.I., Tsong, T.Y., 1978. Cluster model of lipid phase transitions with appli-
cation to passive permeation of molecules and structure relaxations in lipid
bilayers. J. Am. Chem. Soc. 100, 424–432.
Lambros, M.P., Rahman, Y.E., 2004. Effects of cyclosporin A on model lipid mem-
branes. Chem. Phys. Lipids 131, 63–69.
Lewis, R.N.A.H., Mak, N., McElhaney, R.N., 1987. A differential scanning calorimetric
study of the thermotropic phase behavior of model membranes composed of
phosphatidylcholines containing linear saturated fatty acyl chains. Biochemistry
26, 6118–6126.
Liu, Y., Pan, J., Feng, S.-S., 2010. Nanoparticles of lipid monolayer shell and biodegrad-
able polymer core for controlled release of paclitaxel: effects of surfactants
on particles size, characteristics and in vitro performance. Int. J. Pharm. 395,
243–250.
Lohner, K., Prenner, E.J., 1999. Differential scanning calorimetry and X-ray diffrac-
tion studies of the specificity of the interaction of antimicrobial peptides with
membrane–mimetic systems. Biochim. Biophys. Acta 1462, 141–156.
Marsh, D., Watts, A., Knowles, P.F., 1977. Cooperativity of the phase transi-
tion in single and multibilayer lipid vesicles. Biochim. Biophys. Acta 465,
500–514.
Meng, S., Su, B., Li, W., Ding, Y., Tang, L., Zhou, W., Song, Y., Li, H., Zhou, C., 2010.
Enhanced antitumor effect of novel dual-targeted paclitaxel liposomes. Nano-
pp.).
Mu, L., Feng, S.-S., 2003. A novel controlled release formulation for the anticancer
drug paclitaxel (Taxol®): PLGA nanoparticles containing vitamin E TPGS. J. Con-
trol. Release 86, 33–48.
Nanda, R., Sasmal, A., Nayak, P.L., 2011. Preparation and characterization of
chitosan–polylactide composites blended with Cloisite 30B for control release
of the anticancer drug paclitaxel. Carbohydr. Polym. 83, 988–994.
Paolino, D., Celia, C., Trapasso, E., Cilurzo, F., Fresta, M., 2012. Paclitaxel-loaded
ethosomes®: potential treatment of squamous cell carcinoma, a malignant
transformation of actinic keratoses. Eur. J. Pharm. Biopharm. Available online
5 March.
Sarpietro, M.G., Micieli, D., Rocco, F., Ceruti, M., Castelli, F., 2009. Conjugation of squa-
lene to acyclovir improves the affinity for biomembrane models. Int. J. Pharm.
382, 73–79.
Sarpietro, M.G., Ottimo, S., Giuffrida, M.C., Rocco, F., Ceruti, M., Castelli, F., 2011. Syn-
thesis of n-squalenoyl cytarabine and evaluation of its affinity with phospholipid
bilayers and monolayers. Int. J. Pharm. 406, 69–77.
Sarpietro, M.G., Rocco, F., Micieli, D., Ottimo, S., Ceruti, M., Castelli, F., 2010. Interac-
tion of acyclovir and its squalenoyl–acyclovir prodrug with DMPC in monolayers
at the air/water interface. Int. J. Pharm. 395, 167–173.
Sharma, D., Chelvi, T.P., Ralhan, R., 1998. Thermosensitivity liposomal taxol formu-
lation: heat-mediated targeted drug delivery in murine melanoma. Melanoma
Res. 8, 240–244.
References
Ahmad, I., Masters, G.R., Schupsky, J.J., Nguyen, J., Ali, S., Janoff, A.S., Mayhew, E., 1999.
Growth inhibition of a human ovarian tumor by a novel paclitaxel derivative in
SCID mice. Oncol. Res. 11, 273–280.
Alcaro, S., Ventura, C.A., Paolino, D., Battaglia, D., Ortuso, F., Cattel, L., Puglisi, G.,
Fresta, M., 2002. Preparation, characterization, molecular modeling and in vitro
activity of paclitaxel–cyclodextrin complexes. Bioorg. Med. Chem. Lett. 12,
1637–1641.
Ali, S., Minchey, S., Janoff, A., Mayhew, E., 2000. A differential scanning calorimetry
study of phosphocholines mixed with paclitaxel and its bromoacylated taxanes.
Biophys. J. 78, 246–256.
Balasubramanian, S.V., Straubinger, R.M., 1994. Taxol–lipid interactions: taxol-
dependent effects on the physical properties of model membranes. Biochemistry
33, 8941–8947.
Bhardwaj, V., Ankola, D.D., Gupta, S.C., Schneider, M., Lehr, C.-M., Ravi Kumar, M.N.V.,
2009. PLGA nanoparticles stabilized with cationic surfactant Safety studies and
application in oral delivery of paclitaxel to treat chemical-induced breast cancer
in rat. Pharm. Res. 26, 2495–2503.
Castelli, F., Sarpietro, M.G., Micieli, D., Stella, B., Rocco, F., Cattel, L., 2007.
Enhancement of gemcitabine affinity for biomembranes by conjugation with
squalene: differential scanning calorimetry and Langmuir–Blodgett studies
using biomembrane models. J. Colloid Interface Sci. 316, 43–52.
Ceruti, M., Crosasso, P., Brusa, P., Arpicco, S., Dosio, F., Cattel, L., 2000. Preparation,
characterization, cytotoxicity and pharmacokinetics of liposomes containing
water-soluble prodrugs of paclitaxel. J. Control. Release 63, 141–153.
Chakravarthi, S.S., De, S., Miller, D.W., Robinson, D.H., 2010. Comparison of anti-
tumor efficacy of paclitaxel delivered in nano- and microparticles. Int. J. Pharm.
383, 37–44.
Choi, J.-S., Jo, B.-W., 2004. Enhanced paclitaxel bioavailability after oral administra-
tion of pegylated paclitaxel prodrug for oral delivery in rats. Int. J. Pharm. 280,
221–227.
Constantinides, P.P., Tustian, A., Kessler, D.R., 2004. Tocol emulsions for drug solu-
bilization and parenteral delivery. Adv. Drug Deliv. Rev. 56, 1243–1255.
De, S., Miller, D.W., Robinson, D.H., 2005. Effect of particle size of nanospheres and
microspheres on the cellular-association and cytotoxicity of paclitaxel in 4T1
cells. Pharm. Res. 22, 766–775.
Dosio, F., Harivardhan Reddy, L., Ferrero, A., Stella, B., Cattel, L., Couvreur, P., 2010.
Novel nanoassemblies composed of squalenoyl–paclitaxel derivatives: synthe-
sis, characterization, and biological evaluation. Bioconjug. Chem. 21, 1349–1361.
Fjallskog, M.L., Frii, L., Bergh, J., 1993. Is Cremophor, solvent for paclitaxel, cytotoxic?
Lancet 342, 876.
Greenwald, R.B., Choe, Y.H., McGuire, J., Conover, C.D., 2003. Effective drug delivery
by PEGylated drug conjugates. Adv. Drug Deliv. Rev. 55, 217–250.
Greenwald, R.B., Gilbert, C.W., Pendri, A., Conover, C.D., Xia, J., Martinez, A., 1996.
Drug delivery systems: water soluble taxol 2¢-poly(ethylene glycol) ester pro-
drugs design and in vivo effectiveness. J. Med. Chem. 39, 424–431.
Gregoriadis, G., 1988. Liposome as Drug Carriers: Recent Trends and Progress. John
Wiley and Sons, Chichester.
Shieh, M.F., Chu, I.M., Lee, C.J., Kan, P., Hau, D.M., Shieh, J.J., 1997. Liposomal delivery
system for taxol. J. Ferment. Bioeng. 83, 87–90.
Singer, J.W., Baker, B., De Vries, P., Kumar, A., Shaffer, S., Vawter, E., Bolton, M.,
Garzone, P., 2003. Poly-(l)-glutamic acid-paclitaxel (CT-2103) [XYOTAX], a
biodegradable polymeric drug conjugate: characterization, preclinical pharma-
cology, and preliminary clinical data. Adv. Exp. Med. Biol. 519, 81–99.
Skwarczynski, M., Hayashi, Y., Kiso, Y., 2006. Paclitaxel prodrugs: toward smarter
delivery of anticancer agents. J. Med. Chem. 49, 7253–7269.
Torchilin, V.P., 2005. Recent advances with liposomes as pharmaceutical carries. Nat.
Rev. 4, 145–160.
Vyas, D.M., 1995. Paclitaxel (Taxol®) formulation and prodrugs. In: Farina, V. (Ed.),
The Chemistry and Pharmacology of Taxol and its Derivatives. Elsevier Science,
B.V.
Wani, M.C., Taylor, H.L., Wall, M.E., Coggon, P., McPhail, A.T., 1971. Plant antitumor
agents. Part VI. The isolation and structure of taxol, a novel antileukemic and
antitumor agent from Taxus brevifolia. J. Am. Chem. Soc. 93, 2325–2327.
Weiss, R.B., Donehower, R.C., Wiernik, P.H., Ohnuma, T., Gralla, R.J., Trump, D.L., Baker
Jr., J.R., Van Echo, D.A., Von Hoff, D.D., Leyland-Jones, B., 1990. Hypersensitivity
reactions from taxol. J. Clin. Oncol. 8, 1263–1268.
Han, J., Davis, S.S., Papandreou, C., Melia, C.D., Washington, C., 2004.
Design and evaluation of an emulsion vehicle for paclitaxel. I. Physic-
ochemical properties and plasma stability. Pharm. Res. 21, 1573–1580,
Zhao, L., Feng, S.-S., Go, M.L., 2004. Investigation of molecular interactions between
paclitaxel and DPPC by Langmuir film balance and differential scanning
calorimetry. J. Pharm. Sci. 93, 86–98.