Development and Evaluation of Diclofenac Sodium Loaded-N-Trimethyl Chitosan Nanoparticles for Ophthalmic Use

Abstract

The ophthalmic preparation of diclofenac sodium (DC) for relieving ocular inflammation is presently available in the market only as an eye drop solution. Due to its low occular bioavailability, it requires frequent application leading to low patients' compliance and quality of life. This study was conducted to develop formulations of DC loaded-N-trimethyl chitosan nanoparticles (DC-TMCNs) for ophthalmic use to improve ocular biavailabiltiy of DC. DC-TMCNs varied in formulation compositions were prepared using ionic gelation technique and evaluated for their physicochemical properties, drug release, eye irritation potential, and ophthalmic absorption of diclofenac sodium. N-Trimethyl chitosan (TMC) with a 49.8% degree of quaternization was synthesized and used for DC-TMCNs production. The obtained DC-TMCNs had particle size in a range of 130-190 nm with zeta potential values of +4 to +9 mV and drug entrapment efficiencies of more than 70% depending on the content of TMC and sodium tripolyphosphate (TPP). The optimized DC-TMCNs formulation contained TMC, DC, and TPP at a weight ratio of TMC/DC/TPP = 3:1:1. Their lyophilized product reconstituted with phosphate buffer solution pH 5.5 possessed a drug release pattern that fitted within the zero-order model. The eye irritation tests showed that DC-TMCNs were safe for ophthalmic use. The in vivo ophthalmic drug absorption study performed on rabbits indicated that DC-TMCNs could improve ophthalmic bioavailability of DC. Results of this study suggested that DC-TMCNs had potential for use as an alternative to conventional DC eye drops for ophthalmic inflammation treatment.

Ocular delivery of cyanidin-3-glycoside in liposomes and its prevention of selenite-induced oxidative stress

“…TMC has been proved as a potential enhancer in ophthalmic ofloxacin solutions for the topical treatment of endophthalmitis at the concentration of 0.001% w/v 23 . The TMC nanoparticles made by using ionic gelation technique loading with diclofenac sodium could improve ophthalmic bioavailability of diclofenac sodium for ophthalmic inflammation treatment 24 . In our previous work, with the formation of N-trimethyl chitosan chloride (TMC)-coated cationic liposomes, we proved that the obtained cationic liposomes for drugs with poor solubility could reduce rapid precorneal drug loss and improve poor corneal permeability 25,26 .…”

“…To our knowledge, there are few reports on the use of TMC in the application of such formulation loaded with C3G for cataracts treatment 23,24 .…”

A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride

“…18,19 Furthermore, LPs have suitable particle size (PS) and ζ-potential (ZP), which can improve precorneal residence ability and drug uptake. 20 Therefore, LPs may be a good candidate for enhancing the ocular bioavailability of topically administered drugs.…”

“…The data of in vitro release studies were fitted to several drug-releasing models to determine the mechanism of drug release from the Mt-BH-LPs. ) of different volumes (10,20,30,50,80, and 100 µL) with different dissolving times (0.5, 2, and 4 hours) in Dulbecco's Modified Eagle's Medium/F12 were added to the cells (100 µL per well). After 24 hours' exposure, the culture medium was removed and the cell substrate washed with phosphate-buffered saline, and then 180 µL of fresh medium and 20 µL of MTT (5 mg⋅mL ) were added to each well for 4 hours' treatment.…”

“…Mt-Bh liposomes for ophthalmic drug delivery (10,20,30,50,80, 100 µL) for 2 hours was Betoptic  BH  Mt-BH-LPs  blank LPs. From these results, it is clear that Mt-BH-LPs can effectively maintain superior cell viability within an appropriate range.…”