PREPARATION AND EVALUATION OF ANTHRALIN BIODEGRADABLE NANOPARTICLES AS A POTENTIAL DELIVERY SYSTEM FOR THE TREATMENT OF PSORIASIS
Keywords:Anthralin, Nanoparticles, Psoriasis, Poly (caprolactone), Drug delivery, Solubility
Objective: Anthralin is one of the most effective drugs in psoriasis management. However, its side effects and unfavourable physicochemical properties limit its clinical use. Therefore, the objective of this study was to prepare and evaluate poly (ethylene glycol)-block-poly (Îµ-caprolactone) (PEG-b-PCL) nanoparticles as a potential delivery system for anthralin.
Methods: PEG-b-PCL nanoparticles were prepared by the co-solvent evaporation method and evaluated using a variety of techniques. The effect of drug/polymer weight feed ratio on the nanoparticle size, drug loading capacity and encapsulation efficiency were studied. Drug release kinetics were studied using the dialysis bag method. Nanoparticle size was measured using dynamic light scattering and confirmed by transmission electron microscopy measurements.
Results: PEG-b-PCL formed spherical nanoparticles having a diameter of 40 to 80 nm based on the polymer and level of drug loading. The size observed by TEM measurements was slightly smaller than that obtained by DLS due nanoparticle dryness during measurement. Drug loading capacity increased with increasing the drug/polymer ratio and a maximum loading of ~25% was obtained. Anthralin encapsulation in the nano particles resulted in ~120-fold increase in its aqueous solubility. Anthralin was released from the nanoparticles over a prolonged period of time where ~ 45% was released in 48 h.
Conclusion: These results confirm the utility of PEG-b-PCL nanoparticles in enhancing the aqueous solubility and sustaining the release of athralin. Therefore, they might be used as a potential delivery system for the treatment of psoriasis.
Laws PM, Young HS. Update of the management of chronic psoriasis: new approaches and emerging treatment options. Clin Cosmet Invest Dermatol 2010;3:25-37.
Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 2007;370:263-71.
Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol 2014;70:512-6.
De Korte J, Sprangers MA, Mombers FM, Bos JD. Quality of life in patients with psoriasis: a systematic literature review. J Invest Dermatol Symp Proc 2004;9:140-7.
Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol 1999;41:401-7.
Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol 1998;139:846-50.
Parish LC, Millikan LE, Witkowski JA. The modern story of anthralin. Int J Dermatol 1989;28:373-4.
Saraswat A, Agarwal R, Katare OP, Kaur I, Kumar B. A randomized, double-blind, vehicle-controlled study of a novel liposomal dithranol formulation in psoriasis. J Dermatolog Treat 2007;18:40-5.
Agarwal R, Katare OP, Vyas SP. Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int J Pharm 2001;228:43-52.
Mustakallio KK. Irritation, staining and antipsoriatic activity of 10-acyl analogues of anthralin. Br J Dermatol 1981;20:23-7.
Ramsay B, Lawrence CM, Bruce JM, Shuster S. The effect of triethanolamine application on anthralin-induced inflammation and therapeutic effect in psoriasis. J Am Acad Dermatol 1990;23:73-6.
Schaefer H, Farber EM, Goldberg L, Schalla W. Limited application period for dithranol in psoriasis. Preliminary report on penetration and clinical efficacy. Br J Dermatol 1980;102:571-3.
Wilson PD Ive FA. Dithrocream in psoriasis. Br J Dermatol 1980;103:105-6.
Volden G, Bjornberg A, Tegner E, Pedersen NB, Arles UB, Agren S, et al. Short-contact treatment at home with Micanol. Acta Derm Venereol Suppl 1992;172:20-2.
Abdel-Mottaleb MM, Try C, Pellequer Y, Lamprecht A. Nanomedicine strategies for targeting skin inflammation. Nanomedicine (London, England) 2014;9:1727-43.
Soliman GM, Zhang YL, Merle G, Cerruti M, Barralet J. Hydrocaffeic acid-chitosan nanoparticles with enhanced stability, mucoadhesion and permeation properties. Eur J Pharm Biopharm 2014;88:1026-37.
Toh M-R, Chiu GNC. Liposomes as sterile preparations and limitations of sterilisation techniques in liposomal manufacturing. Asian J Pharm Sci 2013;8:88-95.
Sharma A, Soliman GM, Al-Hajaj N, Sharma R, Maysinger D, Kakkar A. Design and evaluation of multifunctional nanocarriers for selective delivery of coenzyme Q10 to mitochondria. Biomacromolecules 2011;13:239-52.
Aliabadi HM, Mahmud A, Sharifabadi AD, Lavasanifar A. Micelles of methoxy poly(ethylene oxide)-b-poly([epsilon]-caprolactone) as vehicles for the solubilization and controlled delivery of cyclosporine A. J Controlled Release 2005;104:301-11.
Soliman GM, Sharma R, Choi AO, Varshney SK, Winnik FM, Kakkar AK, et al. Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on AB miktoarm star polymers. Biomaterials 2010;31:8382-92.
Soliman GM, Attia MA, Mohamed RA. Poly (Ethylene Glycol)-block-Poly(epsilon-Caprolactone) nano micelles for the solubilization and enhancement of antifungal activity of sertaconazole. Curr Drug Delivery 2014;11:753-62.
Soliman GM, Redon R, Sharma A, Mejia D, Maysinger D, Kakkar A. Miktoarm star polymer based multifunctional traceable nanocarriers for efficient delivery of poorly water soluble pharmacological agents. Macromol Biosci 2014;14:1312-24.
Cho EJ, Holback H, Liu KC, Abouelmagd SA, Park J, Yeo Y. Nanoparticle characterization: state of the art, challenges, and emerging technologies. Mol Pharm 2013;10:2093-110.
Mohanty C, Acharya S, Mohanty AK, Dilnawaz F, Sahoo SK. Curcumin-encapsulated MePEG/PCL diblock copolymeric micelles: a novel controlled delivery vehicle for cancer therapy. Nanomedicine 2010;5:433-49.
Gao X, Wang B, Wei X, Rao W, Ai F, Zhao F, et al. Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer. Int J Nanomed 2013;8:971-82.
Liu L, Li CX, Li XC, Yuan Z, An YL, He BL. Biodegradable polylactide/poly (ethylene glycol)/ polylactide triblock copolymer micelles as anticancer drug carriers. J Appl Polym Sci 2001;80:1976-82.
Liu J, Lee H, Allen C. Formulation of drugs in block copolymer micelles: drug loading and release. Curr Pharm Des 2006;12:4685-701.
Modi S, Anderson BD. Determination of drug release kinetics from nanoparticles: overcoming pitfalls of the dynamic dialysis method. Mol Pharm 2013;10:3076-89.
Leo E, Cameroni R, Forni F. Dynamic dialysis for the drug release evaluation from doxorubicinâ€“gelatin nanoparticle conjugates. Int J Pharm 1999;180:23-30.
Fathalla D, Soliman G, Fouad E. Development and in vitro/in vivo evaluation of liposomal gels for the sustained ocular delivery of latanoprost. J Clin Exp Ophthalmol 2015;6:2.