Ufasomes Mediated Cutaneous Delivery of Dexamethasone: Formulation and Evaluation of Anti-Inflammatory Activity by Carrageenin-Induced Rat Paw Edema Model
The purpose of study is to formulate and evaluate ufasomal gel of dexamethasone. Ufasomal suspension was made by sonication method using different concentrations of Span 80, Span 20 and cholesterol along with 25 mg of drug. Ufasomal gel was formulated by hydration method using carbopol 940. Ufasomal vesicles appeared as spherical and multilamellar under Transmission Electron Microscope. Ufasomal formulation prepared with drug to oleic acid molar ratio 8:2 (UF-2) produced greater number of vesicles and greater entrapment efficiency. UF-2 was optimized for further evaluation. The transdermal permeation and skin partitioning of from optimized formulation was significantly higher ( ) as compared to plain drug and plain gel formulation which is due to presence of surfactant acting as permeation enhancer. Permeation of optimized formulation was found to be about 4.7 times higher than plain drug gel. Anti-inflammatory activity evaluated by inhibition Carrageenan induced rat paw edema model. Significant reduction of edema ( ) was observed in comparison to the commercial product. Hence oleic acid based vesicles can be used as alternate carrier for topical delivery. 1. Introduction Dexamethasone is a glucocorticoid with a relevant clinical use mainly due to its anti-inflammatory and immunosuppressive effects. However, the great number of side effects, such as hypertension, hydroelectrolytic disorders, hyperglycemia, peptic ulcers, and glucosuria, restricts the use of dexamethasone in prolonged therapy [1]. Topical administration of dexamethasone is clinically used for the treatment of many ocular disorders, or diseases, like uveitis, [2] allergic conjunctivitis, [3] and corneal postoperative period, [4] as well as for the treatment of skin disorders such as atopic dermatitis, [5, 6] allergic dermatitis, eczematous dermatitis, [6, 7] psoriasis, acne rosacea, [8] and phimosis [9]. Over the last years many efforts have been made not only to improve the efficacy and bioavailability of drugs but also to reduce their adverse effects by means of the development of novel drug carrier systems [10]. In the past few decades, considerable attention has been focused on the development of new drug delivery system (NDDS). When the new drug or existing drug is given by altering the formulation and administered through different route, this process is called the novel drug delivery system. The NDDS should ideally fulfill two prerequisites. Firstly, it should deliver the drug at a rate directed by the needs of the body, over the period of treatment. Secondly, it should channel the
References
[1]
B. P. Schimmer and K. L. Parker, As bases farmacológicas da terapêutica, Impressos Universitária SA, Santiago, Chile, 1996.
[2]
S. Munoz-Fernandez and E. Martin-Mola, “Uveitis,” Best Practice and Research Clinical Rheumatology, vol. 20, no. 3, pp. 487–505, 2006.
[3]
J. Shoji, T. Sakimoto, K. Muromoto, N. Inada, M. Sawa, and C. Ra, “Comparison of topical dexamethasone and topical FK506 treatment for the experimental allergic conjunctivitis model in Balb/c mice,” Japanese Journal of Ophthalmology, vol. 49, no. 3, pp. 205–210, 2005.
[4]
F. Yülek, S. Ozdek, G. Gurelik, and B. Hasanreisoglu, “Effect of topical steroids on corneal epithelial healing after vitreoretinal surgery,” Acta Ophthalmologica Scandinavica, vol. 84, no. 3, pp. 319–322, 2006.
[5]
K. Matsumoto, K. Mizukoshi, M. Oyobikawa, H. Ohshima, Y. Sakai, and H. Tagami, “Objective evaluation of the efficacy of daily topical applications of cosmetics bases using the hairless mouse model of atopic dermatitis,” Skin Research and Technology, vol. 11, no. 3, pp. 209–217, 2005.
[6]
A. Trautmann, M. Akdis, P. Schmid-Grendelmeier et al., “Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis,” Journal of Allergy and Clinical Immunology, vol. 108, no. 5, pp. 839–846, 2001.
[7]
C. Levin and H. I. Maibach, “Clinical value of corticosteroids in acute and cumulative experimental irritant dermatitis in man,” Dermatologie in Beruf und Umwelt, vol. 48, no. 5, pp. 179–182, 2000.
[8]
I. C. Valencia and F. A. Kerdel, “Topical corticosteroids Fitzpatrick's dermatology in general medicine,” in Em Fitzpatrick’s Dermatology in General Medicine, I. M. Freedberg, A. Z. Eisen, K. Wolff, K. F. Austen, L. A. Goldsmith, and S. Katz, Eds., pp. 2585–2595, McGraw-Hill Professional, New York, NY, USA, 2003.
[9]
N. Zampieri, M. Corroppolo, V. Zuin, S. Bianchi, and F. S. Camoglio, “Phimosis and topical steroids: new clinical findings,” Pediatric Surgery International, vol. 23, no. 4, pp. 331–335, 2007.
[10]
A. Kidane and P. Bhatt, “Recent advances in small molecule drug delivery,” Current Opinion in Chemical Biology, vol. 9, no. 4, pp. 347–351, 2005.
[11]
V. H. K. Li, J. R. Robinson, and V. H. L. Lee, Controlled Drug Delivery: Fundamentals and Applications, vol. 29, Marcel Dekker, New York, NY, USA, 2nd edition, 1987.
[12]
E. W. Smith and H. I. Maibach, “Percutaneous penetration enhancers: the fundamental,” in Percutaneous Penetration Enhancers, E. W. Smith and H. I. Maibach, Eds., pp. 1–4, CRC Press, Boca Raton, Fla, USA, 1995.
[13]
J. M. Gebicki and M. Hicks, “Ufasomes are stable particles surrounded by unsaturated fatty acid membranes,” Nature, vol. 243, no. 5404, pp. 232–234, 1973.
[14]
W. R. Hargreaves, “Liposomes from ionic, single-chain amphiphiles,” Biochemistry, vol. 17, no. 18, pp. 3759–3768, 1978.
[15]
M. L. Rogerson, P. Walde, B. H. Robinson, and S. Bucak, “Kinetic studies of the interaction of fatty acids with phosphatidylcholine vesicles (liposomes),” Colloids and Surfaces B, vol. 48, no. 1, pp. 24–34, 2006.
[16]
M. Murakami, H. Yoshikawa, K. Takada, and S. Muranishi, “Effect of oleic acid vesicles on intestinal absorption of carboxyfluorescein in rats,” Pharmaceutical Research, vol. 3, no. 1, pp. 35–40, 1986.
[17]
A. Naik, L. A. R. M. Pechtold, R. O. Potts, and R. H. Guy, “Mechanism of oleic acid-induced skin penetration enhancement in vivo in humans,” Journal of Controlled Release, vol. 37, no. 3, pp. 299–306, 1995.
[18]
B. J. Aungst, “Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants,” Pharmaceutical Research, vol. 6, no. 3, pp. 244–247, 1989.
[19]
N. Kanikkannan, K. Kandimalla, S. S. Lamba, and M. Singh, “Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery,” Current Medicinal Chemistry, vol. 7, no. 6, pp. 593–608, 2000.
[20]
J. Guo, Q. Ping, G. Sun, and C. Jiao, “Lecithin vesicular carriers for transdermal delivery of cyclosporin A,” International Journal of Pharmaceutics, vol. 194, no. 2, pp. 201–207, 2000.
[21]
G. M. M. El Maghraby, A. C. Williams, and B. W. Barry, “Skin hydration and possible shunt route penetration in controlled estradiol delivery from ultradeformable and standard liposomes,” Journal of Pharmacy and Pharmacology, vol. 53, no. 10, pp. 1311–1322, 2001.
[22]
M. Singh, M. P. Singh, S. N. Maiti, A. Gandhi, R. G. Micetich, and H. Atwal, “Preparations of liposomal fluconazole and their in vitro antifungal activity,” Journal of Microencapsulation, vol. 10, no. 2, pp. 229–236, 1993.
[23]
S. S. Zao, Q. Du, and D. Y. Cao, “Preparation of liposomal fluconazole gel and in vitro transdermal delivery,” Journal of Chinese Pharmaceutical Sciences, vol. 16, pp. 116–118, 2007.
[24]
S. Jain, P. Jain, R. B. Umamaheshwari, and N. K. Jain, “Transfersomes—a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation,” Drug Development and Industrial Pharmacy, vol. 29, no. 9, pp. 1013–1026, 2003.
[25]
R. C. R. Beck, S. S. Guterres, R. J. Freddo, C. B. Michalowski, I. Barcellos, and J. A. B. Funck, “Nanoparticles containing dexamethasone: physicochemical properties and anti-inflammatory activity,” Acta Farmaceutica Bonaerense, vol. 22, no. 1, pp. 11–15, 2003.
[26]
S. B. Kulkarni, M. Singh, and G. V. Betageri, “Encapsulation, stability and in-vitro release characteristics of liposomal formulations of colchicine,” Journal of Pharmacy and Pharmacology, vol. 49, no. 5, pp. 491–495, 1997.
[27]
J. Lasch, R. Laub, and W. Wohlrab, “How deep do intact liposomes penetrate into human skin?” Journal of Controlled Release, vol. 18, no. 1, pp. 55–58, 1992.
[28]
O. López, A. de la Maza, L. Coderch, C. López-Iglesias, E. Wehrli, and J. L. Parra, “Direct formation of mixed micelles in the solubilization of phospholipid liposomes by Triton X-100,” FEBS Letters, vol. 426, no. 3, pp. 314–318, 1998.
[29]
R. Lobenberg and J. Kreuter, “Macrophage targeting of azidothymidine: a promising strategy for AIDS therapy,” AIDS Research and Human Retroviruses, vol. 12, no. 18, pp. 1709–1715, 1996.
[30]
S. Jain, N. Jain, D. Bhadra, A. K. Tiwary, and N. K. Jain, “Transdermal delivery of an analgesic agent using elastic liposomes: preparation, characterization and performance evaluation,” Current Drug Delivery, vol. 2, no. 3, pp. 223–233, 2005.
[31]
D. P. Cistola, J. A. Hamilton, D. Jackson, and D. M. Small, “lonization and phase behavior of fatty acids in water: application of the Gibbs phase rule,” Biochemistry, vol. 27, no. 6, pp. 1881–1888, 1988.
[32]
P. Walde, T. Namani, K. Morigaki, and H. Hauser, “Formation and properties of fatty acid vesicles (liposomes),” in Liposome Technology, G. Gregoriadis, Ed., pp. 1–20, Informa Healthcare, New York, NY, USA, 3rd edition, 2007.
[33]
C. L. Apel, D. W. Deamer, and M. N. Mautner, “Self-assembled vesicles of monocarboxylic acids and alcohols: conditions for stability and for the encapsulation of biopolymers,” Biochimica et Biophysica Acta, vol. 1559, no. 1, pp. 1–9, 2002.
[34]
M. B. Dowling, J. H. Lee, and S. R. Raghavan, “pH-responsive jello: gelatin gels containing fatty acid vesicles,” Langmuir, vol. 25, no. 15, pp. 8519–8525, 2009.
[35]
P. L. Luisi, P. Walde, M. Blocher, and E. Blochliger, “Matrix effect in the size distribution of fatty acid vesicles,” The Journal of Physical Chemistry B, vol. 102, no. 50, pp. 10383–10390, 1998.
[36]
R. M. Hathout, S. Mansour, N. D. Mortada, and A. S. Guinedi, “Liposomes as an ocular delivery system for acetazolamide: in vitro and in vivo studies,” AAPS PharmSciTech, vol. 8, no. 1, pp. E1–E12, 2007.
[37]
M. Nasr, S. Mansour, N. D. Mortada, and A. A. Elshamy, “Vesicular aceclofenac systems: a comparative study between liposomes and niosomes,” Journal of Microencapsulation, vol. 25, no. 7, pp. 499–512, 2008.
[38]
G. Lawrie, I. Keen, B. Drew et al., “Interactions between alginate and chitosan biopolymers characterized using FTIR and XPS,” Biomacromolecules, vol. 8, no. 8, pp. 2533–2541, 2007.
[39]
C. E. Creutz, “Cis-unsaturated fatty acids induce the fusion of chromaffin granules aggregated by synexin,” Journal of Cell Biology, vol. 91, no. 1, pp. 247–256, 1981.
[40]
P. W. Choppin and D. S. Roos, “Biochemical studies on cell fusion. II. Control of fusion response by lipid alteration,” Journal of Cell Biology, vol. 101, no. 4, pp. 1591–1598, 1985.
