FORMULATION AND CHARACTERIZATION OF TIMOLOL MALEATE-LOADED NANOPARTICLES GEL BY IONIC GELATION METHOD USING CHITOSAN AND SODIUM ALGINATE
Keywords:Timolol maleate, Nanoparticles, Infantile hemangioma
Objective: The objectives of this study were to formulate and characterize nanoparticles gel of timolol maleate (TM) by ionic gelation method using chitosan (CS) and sodium alginate (SA).
Methods: Optimization was carried out by factorial design using Design Expert®10.0.1 software to obtain the concentration of CS, SA, and calcium chloride (CaCl2) to produce the optimum formula of TM nanoparticles. The optimum formula was characterized for particle size, polydispersity index, entrapment efficiency, Zeta potential, and molecular structure. Hydroxy Propyl Methyl Cellulose (HPMC) K15 was incorporated into optimum formula to form nanoparticles gel of TM and carried out in vivo release study using the Franz Diffusion Cell.
Results: TM nanoparticles was successfully prepared with concentration of CS, SA, and CaCl2 of 0.01 % (w/v), 0.1 % (w/v), and 0.25 % (w/v), respectively. The particle size, polydispersity index, entrapment efficiency, and Zeta potential were found to be 200.47±4.20 nm, 0.27±0.0154, 35.23±4.55 %, and-5.68±1.80 mV, respectively. The result of FTIR spectra indicated TM-loaded in the nanoparticles system. In vitro release profile of TM-loaded nanoparticles gel showed controlled release and the Korsmeyer-Peppas model was found to be the best fit for drug release kinetics.
Conclusion: TM-loaded CS/SA nanoparticles gel was successfully prepared and could be considered as a promising candidate for controlled TM delivery of infantile hemangioma treatment.
Ariwibowo L, Budiyanto A, Danarti R. Efikasi terapi topikal kortikosteroid ultrapoten, solusio, dan gel timolol maleat 0,5% terhadap hemangioma infantil superfisial. Sari Pediatri 2016;17:428-34.
Pope E, Krafchik BR, Macarthur C, Stempak D, Stephens D, Weinstein M. Oral versus high dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial. Pediatrics 2007;119:1239-47.
Callahan AB, Yoon MK. Infantile hemangiomas: a review. Saudi J Ophthalmol 2012;26:283–91.
Weissenstein A, Straeter A, Villalon G, Bittmann S. Topical timolol for small infantile hemangioma: a new therapy option. Turk J Pediat 2012;54:156-8.
Danarti R, Ariwibowo L, Radiono S, Budiyanto A. Topical timolol maleate 0.5% for infantile hemangioma: its effectiveness compared to ultrapotent topical corticosteroids-a single center experience of 278 cases. Dermatology 2016;232:566–71.
McMahon P, Oza V, Frieden IJ. Topical timolol for infantile hemangiomas: putting a note of caution in “cautiously optimistic”: commentary. Pediatric Dermatol 2012;29:127–30.
Mohanraj VJ, Chen Y. Nanoparticles-a review. Trop J Pharm Res 2006;5:561-73.
Sarangi MK, Padhi S. Solid lipid nanoparticles–a review. J Crit Rev 2016;3:5-12.
Kasar PD, Kale KS, Phadtare DG. Nanoplex: a review of nanotechnology approach for solubility and dissolution rate enhancement. Int J Curr Pharm Res 2018;10:6-10.
Lertsutthiwong P, Rojsitthisak P. Chitosan-alginate nanocapsules for encapsulation of tumeric oil. Pharmazie 2011;66:911–5.
Martien R, Irianto IDK, Farida V, Sari P. Perkembangan teknologi nanopartikel sebagai sistem penghantaran obat. Majalah Farmaseutik 2012;8:134-44.
Li P, Dai YN, Zhang JP, Wang AQ, Wei Q. Chitosan-alginate nanoparticles as a novel drug delivery system for nifedipine. Int J Biomed Sci 2008;4:221-8.
Muhtadi WK, Novitasari L, Martien R, Danarti R. Factorial design as the method in the optimization of timolol maleate-loaded nanoparticle prepared by ionic gelation technique. Int J Appl Pharm 2019;11:66-70.
Ilka R, Mohseni M, Kianirad M, Naseripour M, Ashtari K, Mehravi B. Nanogel-based natural polymers as smart carriers for the controlled delivery of timolol maleate through the cornea for glaucoma. Int J Biol Macromol 2018;109:955–62.
Daemi H, Barikani M. Synthesis and characterization of calcium alginate nanoparticles, sodium homopolymannuronate salt and its calcium nanoparticles. Sci Iranica 2012;19:2023–8.
Manish K, Kulkarni GT. Development and process optimization of variables for preparation of novel polymeric nanoparticles containing azelastine hydrochloride. J Pharm Res 2012;5:4884-7.
Raditya I, Effiniora A, Mahdi J. Preparasi nanogel verapamil hidroklorida menggunakan metode gelasi ionik antara kitosan-natrium tripolifosfat sebagai sediaan antihipertesi. Jurnal Farmasi Indonesia 2013;6:201-10.
Pham DT, Saelim S, Tiyaboonchai W. Design of experiments model for the optimization of silk fibroin based nanoparticles. Int J Appl Pharm 2018;10:195-201.
Galih P, Ronny M, Retno M. Chitosan nanoparticle as a delivery system for polyphenols from meniran extract (Phyllanthus niruri L.): formulation, optimization, and immunomodulatory activity. Int J Appl Pharm 2019;11:50-8.
Sumathi R, Tamizharasi S, Sivakumar T. Formulation and evaluation of polymeric nanosuspension of naringenin. Int J Appl Pharm 2017;9:60-70.
Manimekalai P, Dhanalakshmi R, Manavalan R. Preparation and characterization of ceftriaxone sodium encapsulated chitosan nanoparticles. Int J Appl Pharm 2017;9:10-5.
Morsi N, Ghorab D, Refai H, Teba H. Preparation and evaluation of alginate/chitosan nanodispersions for ocular delivery. Int J Pharm Pharm Sci 2015;7:234-40.
Huang J, Peng T, Li Y, Zhan Z, Zeng Y, Huang Y, et al. Ocular cubosome drug delivery system for timolol maleate: preparation, characterization, cytotoxicity, ex vivo, and in vivo evaluation. AAPS PharmSciTech 2017;18:2919-26.
Yap KYL, Chan SY, Lim CS. Infrared-based protocol for the identification and categorization of ginseng and its products. Food Res Int 2007;40:643–52.
Hussain Z, Sahudin S. Preparation, characterisation and colloidal stability of chitosan-tripolyphosphate nanoparticles: optimisation of formulation and process parameters. Int J Pharm Pharm Sci 2016;8:297-308.
Chaiyasan W, Srinivas SP, Tiyaboonchai W. Development and characterization of topical ophthalmic formulations containing lutein-loaded mucoadhesive nanoparticles. Int J Pharm Pharm Sci 2016;8:261-6.
Sarkar T, Ahmed AB. Development and in vitro characterisation of chitosan loaded paclitaxel nanoparticle. Asian J Pharm Clin Res 2016;9 Suppl 3:145-8.
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25–35.
Mukhopadhyay P, Chakrabortya S, Bhattacharyab S, Mishrab R, Kundua PP. pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery. Int J Bio Macromol 2015;72:640–8.
Nagarwal RC, Kumar R, Pandit JK. Chitosan coated sodium alginate–chitosan nanoparticles loaded with 5-FU for ocular delivery: in vitro characterization and in vivo study in rabbit eye. Eur J Pharm Sci 2012;47:678–85.