Preparation and evaluation of nanoparticles for ocular delivery of diclofenac sodium

  • Naz Jamal Ibrahim Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
  • Tara Abdulrahman Abdullah Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Keywords: Chondroitin sulfate (CS), Chitosan (CH), Nanoparticles (NPs), Diclofenac sodium (DS)


Background and objective: Ocular drug delivery research is challenging due to the presence of anatomical and physiological barriers. The ophthalmic preparation of diclofenac sodium (DC) for relieving ocular inflammation is presently available in the market only as an eye drop solution with low ocular bioavailability. The goal of our study was to prepare and evaluate an eye drop formulation, containing a nanocarrier, chondroitin sulfate (CS)-chitosan (CH)-nanoparticles (NPs) (CS/ CH-NPs) is being evaluated for improving the bioavailability of diclofenac sodium into the eye.

Methods: Formulation was developed and optimized for three different variables (chondroitin sulfate, chitosan, and initial drug concentration). The developed formula was evaluated by various in-vitro parameters such as particles' size, entrapment efficacy, zeta potential, and in vitro release profile.

Results: The particles' size, entrapment efficacy, and zeta potential of the best formulation were found to be 251.1±15.12nm, 73.2±5.3%, and 38.89±5.05mV, respectively. Furthermore, the best formulation showed a biphasic release profile, initial burst release in the first hour, followed by sustained release within 24hours.

Conclusion: Promising results of in-vitro studies indicated that CS-CH-NPs could be a potential substitute for improved ocular delivery of diclofenac sodium.


Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol 2013; 2:47–64.

Teodora I, Mihaela VG, Lacramioara P, Valentina A, Andreea-Letitia A, Cristina-Elena D. Strategies for improving ocular drug bio availability and corneal wound healing with chitosan-based delivery systems. Polymers 2018; 10:221.

Baranowski P, Karolewicz B, Gajda M, Pluta J. Ophthalmic Drug Dosage Forms: Characterisation and Research Methods. Sci. World J 2014; 2014:1–14.

Rupenthal ID. Ocular Drug Delivery Technologies: Exciting Times Ahead. ON drug Delivery 2015; 54:7–11.

Anita U, Lidia T. Design of chondroitin sulfate- based polyelectrolyte nanoplexes: Formation of nanocarriers with chitosan and a case study of salmon calcitonin. Carbohydr Polym 2017; 156:276–84.

Ali M. Nanocarriers of nanotechnology in retinal diseases. Saudi J Ophthalmol 2014; 28:304–9.

Guinedi AS, Mortada ND, Mansour S, Hathout RM. Preparationand evaluation of reverse-phase evaporation and multilamellarniosomes as ophthalmic carriers of acetazolamide. Int J Pharm 2005; 306:71–82.

Gupta H, Jain S, Mathur R, Mishra P, Mishra AK, Velpandian T. Sustained ocular drug delivery from a temperature and pH triggered novel in situ gel system. Drug Deliv 2007; 14:507–15.

De la Fuente M, Ravina M, Paolicelli P, Sanchez A, Seijo B, Alonso MJ. Chitosan-based nanostructures: a delivery platform for ocular therapeutic chitosan [J]. Adv Drug Deliv Rev 2010; 62(1):100–17.

Mun EA, Morrison PWJ, Williams AC, Khutoryanskiy VV. On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein [J]. Mol Pharm 2014; 11(10):3556–64.

Chen WB, Wang LF, Chen JS, Fan SY. Characterization of polyelectrolyte complexes between chondroitin sulfate and chitosan in the solid state. J Biomed Mater Res 2005; 75(1):128–37.

Kouchak M, Avadi M, Abbaspour M, Jahangiri A, Kargar Boldaji S. Effect of different molecular weights of chitosan on preparation and characterization of insulin loaded nanoparticles by ion gelation method. Int J Drug Dev Res 2012; 4(2):271–7.

Vicekjot B, Gurpreet K. Preparation and characterization of polyelectrolyte complexes of Hibiscus esculentus (Okra) gum and chitosan. Int J Biomater 2018; 2018:4856287.

Thunemann AF, Müller M, Dautzenberg H, Joanny J, Löwen H. Polyelectrolytes with Defined Molecular Architecture II. Vol. 166. Berlin, Heidelberg: Springer Berlin Heidelberg: Polyelectrolyte Complexes; 2004. P. 113–71 (Advances in Polymer Science).

Araújo J, Gonzalez E, Egea MA, Garcia ML, Souto EB. Nanomedicines for ocular NSAIDs: safety on drug delivery. Nanomedicine 2009; 5:394–401.

Ahuja M, Sharma SK, Majumdar DK. In vitro corneal permeation of diclofenac from oil drops. Yakugaku Zasshi 2007; 127:1739–45.

Attama AA, Reichl S, Müller-Goymann CC. Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int J Pharm 2008; 355:307–13.

Agnihotri SM, Vavia PR. Diclofenac-loaded bio-polymericnano-suspensions for ophthalmic application. Nanomedicine 2009; 5:90–5.

Yosra A, Jiaxin L, Sujay P, Ali S, IIva D. Nanoparticle cross-linked collagen shields for sustained delivery of pilocarpine hydrochloride. Int J Pharm 2016; 501:96–101.

Kirandeep K, Gurpreet K. Formulation and evaluation of chitosan- chondroitin sulfate based nasal inserts for zolmitriptan. BioMed Res Int 2013; 2013:958465.

Chander PD, Shailendra KS, Sanjeev K, Ashok KD, Aakash D. Development and characterization of nanoparticles of Glibenclamide by solvent displacement method. Acta Poloniae Pharmaceutica- drug Research 2010; 67(2):283–90.

Kaskoos RA. Investigation of moxifloxacin loaded chitosan-dextran nanoparticles for topical instillation into eye: In-vitro and ex- vivo evaluation. Int J Pharm Investg 2014;4:167–73.

Aydin RS, Mehlika Pulat. 5-Fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: Evaluation of controlled release kinetics. J Nanomater 2012; 2012:313961.

Usha G, Sree H, Balakeshwa R, Prakash R. Improved intraocular bioavailability of ganciclovir by mucoadhesive polymer based ocular microspheres: development and simulation process in Wister rats. Daru Journal of Pharmaceutical Sciences 2015; 23(1):49.

Ameeduzzafar, Ali J, Bhatnagar A, Kumar N, Ali A. Chitosan nanoparticles amplify the ocular hypotensive effect of cateolol in rabbits. Int J Biol Macromol 2014; 65:479–91.

Javier PQ, Hazel P, Carlos P. Chitosan based self-assembled nanoparticles in drug delivery. Polymers 2018; 10(3):235.

Megha A, Negar DP, Nalini S, Agarwal MK. Chitosan nanoparticles based drug delivery: An update. IJAMR 2015; 2(4):1–13.

How to Cite
Ibrahim, N., & Abdullah, T. (2019). Preparation and evaluation of nanoparticles for ocular delivery of diclofenac sodium. Zanco Journal of Medical Sciences (Zanco J Med Sci), 23(2), 290-298.
Original Articles