A Novel Approach of Drug Localization through Development of Polymeric Micellar System Containing Azelastine HCl for Ocular Delivery

Author(s): Sheetal Devi, Vipin Saini, Manish Kumar*, Shailendra Bhatt, Sumeet Gupta, Aman Deep.

Journal Name: Pharmaceutical Nanotechnology

Volume 7 , Issue 4 , 2019

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Abstract:

Background: Development of polymeric micelles for the management of allergic conjunctivitis to overcome the limitations of topical installation, such as poor patient compliance, poor stromal permeability, and significant adverse effects, increase precorneal residence time and efficacy, and also control the release of drug at the target site.

Objective: The investigation was aimed at developing a polymeric micellar system of Azelastine HCl for Ocular Delivery.

Methods: Drug loaded micelles of tri-block copolymers Pf 127 were prepared by Thin Film hydration method. The polymeric micelles formulations (F1 to F9) were assessed for entrapment efficiency, micelle size, in vitro permeation, ex vivo transcorneal permeation, in vivo Ocular Irritation, and Histology.

Results: Optimized micelles formulation (F3), with the lowest micelle size of 92 nm, least polydispersity value of 0.135, highest entrapment efficiency of 95.30 ± 0.17%, and a cumulative drug permeation of 84.12 ± 1.26% in 8h, was selected to develop pH-sensitive micelles loaded carbopol in situ gel. The optimized in situ gel (G4) proved to be superior in its ex vivo transcorneal permeation when compared with Market Preparation and pure drug suspension, exhibiting 43.35 ± 1.48% Permeation with zero-order kinetics (r2 = 0.9944) across goat cornea. Transmission Electron microscopy revealed spherical polymeric micelles trapped in the gel matrix. A series of experiments showed hydration capability, non-irritancy, and histologically safe gel formulation that had appropriate handling characteristics.

Conclusion: A controlled release pH-sensitive ocular formulation capable of carrying the drug to the anterior section of the eye via topical delivery was successfully developed for the treatment of allergic conjunctivitis.

Keywords: Azelastine HCl, entrapment efficiency, ex vivo transcorneal permeation, histology, in vitro permeation, in vivo ocular irritation, transmission electron microscopy, tri-block copolymers.

[1]
Kuno N, Fujii S. Recent advances in ocular drug delivery systems. Polymers 2011; 3(1): 193-221.
[2]
Danion A, Arsenault I, Vermette P. Antibacterial activity of contact lenses bearing surface-immobilized layers of intact liposomes loaded with levofloxacin. J Pharm Sci 2007; 96(9): 2350-63.
[3]
Lavik E, Kuehn MH, Kwon YH. Novel drug delivery systems for glaucoma. Eye 2011; 25(5): 578-86.
[4]
Short BG. Safety evaluation of ocular drug delivery formulations: techniques and practical considerations. Toxicol Pathol 2008; 36(1): 49-62.
[5]
Gulsen D, Chauhan A. Ophthalmic drug delivery through contact lenses. Invest Ophthalmol Vis Sci 2004; 45(7): 2342-7.
[6]
Gulsen D, Chauhan A. Dispersion of microemulsion drops in HEMA hydrogel: a potential ophthalmic drug delivery vehicle. Int J Pharm 2005; 292(1-2): 95-117.
[7]
Kapoor Y, Chauhan A. Ophthalmic delivery of Cyclosporine A from Brij-97 microemulsion and surfactant-laden p-HEMA hydrogels. Int J Pharm 2008; 361(1-2): 222-9.
[8]
Kim J, Chauhan A. Dexamethasone transport and ocular delivery from poly(hydroxyethyl methacrylate) gels. Int J Pharm 2008; 353(1-2): 205-22.
[9]
Li CC, Chauhan A. Modeling ophthalmic drug delivery by soaked contact lenses. Ind Eng Chem Res 2006; 45(10): 3718-34.
[10]
Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today 2008; 13(3-4): 135-43.
[11]
Jain MR. Drug delivery through soft contact lenses. Br J Ophthalmol 1988; 72(2): 150-4.
[12]
Schultz C, Breaux J, Schentag J, Morck D. Drug delivery to the posterior segment of the eye through hydrogel contact lenses. Clin Exp Optom 2011; 94(2): 212-8.
[13]
Dart JK, Buckley RJ, Monnickendan M, Prasad J. Perennial allergic conjunctivitis: definition, clinical characteristics and prevalence. A comparison with seasonal allergic conjunctivitis. Trans Ophthalmol Soc U K 1986; 105(Pt 5): 513-20.
[14]
Leonardi A, Secchi AG. Vernal keratoconjunctivitis. Int Ophthalmol Clin 2003; 43(1): 41-58.
[15]
Bielory B, Bielory L. Atopic dermatitis and keratoconjunctivitis. Immunol Allergy Clin North Am 2010; 30(3): 323-36.
[16]
Shinde UA, Shete JN, Nair HA, Singh KH. Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride. J Microencapsul 2012; 29(6): 511-9.
[17]
McTavish D, Sorkin EM. Azelastine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1989; 38(5): 778-800.
[18]
Lassig W, Wober W, Höflich C, Bähre M, Roloff A. Topical therapy of allergic rhinitis in childhood: Allergodil nasal spray--non-sedating in children. Curr Med Res Opin 1996; 13(7): 391-5.
[19]
Rosario N, Bielory L. Epidemiology of allergic conjunctivitis. Curr Opin Allergy Clin Immunol 2011; 11(5): 471-6.
[20]
Lenhard G, Mivsek-Music E, PerrinFayolle M, Secchi A. Double-blind, randomised, placebo controlled study of two concentrations of azelastine eye drops in seasonal allergic conjunctivitis or rhinoconjunctivitis Curr Med Res Opin 1997; 14(1): 2 1-8.
[21]
Jiang W, Wang YD, Gan Q. Preparation and characterization of copolymer micelles formed by poly (ethylene glycol)-polylactide block copolymers as novel drug carriers. CJPE 2006; 6: 289-95.
[22]
Wu Y, Yang W, Wang C, Hu J, Fu S. Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate. Int J Pharm 2005; 295(1-2): 235-45.
[23]
Known SK, Kim SY, Ha KW, et al. Pharmaceutical evaluation of Genistein-loaded pluronic micelles for oral delivery. Pharm Res 2007; 30(9): 1138-43.
[24]
Patel R, Patel H. Formulation and evaluation of carbopol gel containing liposomes of ketoconazole. Int J Drug Deliv Tech 2009; 1: 42-5.
[25]
Suryawanshi SS, Kunjwani HK, Kawade JV, Alkunte MA, Yadav DJ. Novel polymeric in-situ gels for ophthalmic drug delivery system. Int J Res Pharm Sci 2012; 2: 67-83.
[26]
Jaiswal M, Kumar M, Pathak K. Zero order delivery of itraconazole via polymeric micelles incorporated in situ ocular gel for the management of fungal keratitis. Colloids Surf B Biointerfaces 2015; 130: 23-30.
[27]
Sun Y, Du L, Liu Y, et al. Transdermal delivery of the in situ hydrogels of curcumin and its inclusion complexes of hydroxypropyl-β-cyclodextrin for melanoma treatment. Int J Pharm 2014; 469(1): 31-9.
[28]
Ammar HO, Salama HA, Ghorab M, Mahmoud AA. Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery. Drug Dev Ind Pharm 2010; 36(11): 1330-9.
[29]
Li J, Wu L, Wu W, et al. A potential carrier based on liquid crystal nanoparticles for ophthalmic delivery of pilocarpine nitrate. Int J Pharm 2013; 455(1-2): 75-84.
[30]
Kumar P, Mohan C, Kanamsrinivasan Uma Shankar M, Gulati M. Physiochemical characterization and release rate studies of soliddispersions of ketoconazole with pluronic F127 and PVP K-30. Iran J Pharm Res 2011; 10(4): 685-94.
[31]
Shawn CO, Dianna PYC, Shoichet MS. Polymeric micelle stability. Nano Today 2011; 7: 53-65.
[32]
Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release 2002; 82(2-3): 189-212.
[33]
Vaidya FU, Sharma R, Shaikh S, Ray D, Aswal VK. Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibit pro-inflammatory cytokines in human breast adenocarcinoma cells. Cancer Rep 2018; 2(1): 1-17.
[34]
Zhao X, Poon Z, Engler AC, Bonner DK, Hammond PT, Paula T. Enhanced stability of polymeric micelles based on postfunctionalized poly(ethylene glycol)-b-poly(γ-propargyl L-glutamate): the substituent effect. Biomacromolecules 2012; 13(5): 1315-22.
[35]
Sahoo SK, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discov Today 2008; 13(3-4): 144-51.
[36]
Khalil RM, Abdelbary GA, Basha M, Awad GEA, El-Hashemy HA. Enhancement of lomefloxacin HCL ocular efficacy via niosomal encapsulation: in vitro characterization and in vivo evaluation. J Liposome Res 2017; 27(4): 312-23.


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Article Details

VOLUME: 7
ISSUE: 4
Year: 2019
Page: [314 - 327]
Pages: 14
DOI: 10.2174/2211738507666190726162000

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