Analysis of 2-oxothiazolidine-4-carboxylic acid by hydrophilic interaction liquid chromatography: application for ocular delivery using chitosan nanoparticles

Abstract

Oxidative damage due to low levels of glutathione (GSH) is one of the main causes of cataract formation. It has been reported that 2-oxothiazolidine-4-carboxylic acid (OTZ), a cysteine prodrug, can increase the cellular level of GSH. Currently, there is no analytical method to separate and quantify OTZ from aqueous humour samples for cataract research. The present study aims to develop and validate a hydrophilic interaction liquid chromatography (HILIC) method for the quantification of OTZ in simulated aqueous humour (SAH). The developed method was validated according to FDA guidelines. Accuracy, precision, selectivity, sensitivity, linearity, lower limit of quantification (LLOQ), lower limit of detection (LLOD) and stability were the parameters assessed in the method validation. The developed method was found to be accurate and precise with LLOQ and LLOD of 200 and 100 ng/mL, respectively; method selectivity was confirmed by the absence of any matrix interference with the analyte peak. The constructed calibration curve was linear in the range of 0.2-10 μg/mL, with a regression coefficient of 0.999. In addition, the OTZ was found to be stable in SAH after three freeze/thaw cycles. Chitosan nanoparticles loaded with OTZ were formulated by the ionic gelation method. The nanoparticles were found to be uniform in Analytical and Bioanalytical Chemistry 407 (8) (2015) 2645-2659. 10.1007/s00216-015-8494-8 ISSN 1618-2642 (Print), 1618-2650 (Online) Published 10 Feb 2015 2 shape and well dispersed with average size of 153 nm. The in vitro release of OTZ from the nanoparticles was quantified using the developed analytical method over 96 h. Permeation of OTZ through excised bovine cornea was measured using HILIC. The lag time and the flux were 0.2 h and 3.05 μg/cm 2 h, respectively.

Characterization of drug delivery vehicles using atomic force microscopy: current status

“…Using different formulation methods, aggregations of nanoparticles were observed using AFM that were not visible employing other techniques. AFM revealed nanoparticles of chitosan containing 2-oxothiazolidine-4-carboxylic acid for ocular delivery to be spherical, of uniform shape and with limited aggregation, supporting SEM investigations [57]. [58]; however, these sizes were smaller than those measured using laser diffraction measurements and this was attributed to sample drying and a slight flattening effect caused by the AFM probe.…”

A hybrid ocular delivery system of cyclosporine-A comprising nanomicelle-laden polymeric inserts with improved efficacy and tolerability

“…A blank sample was introduced between the analyses; the absence of any interference between the matrix peaks with the analyte peaks was considered an acceptable indication of method selectivity. Finally, linear regression analysis was used to test for method linearity [12]. The calibration curve in acetonitrile was linear (r 2 =1) over the concentration range studied (0.05 -10.0 µg/mL).…”

Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments

“…Ganciclovir [156], indomethacin [133], and L-2-oxothiazolidine-4-carboxylic acid [157] were also encapsulated in CS NPs for cataract treatment. Kalam et al studied the encapsulation and in vitro release of indomethacin from CS NPs [133].…”

“…Several drugs have been loaded in CS NPs aiming at treating various eye conditions: levofloxacin [ 135 , 152 , 153 ] and diclofenac [ 131 ] as antibacterial factors; lomefloxacin [ 140 ], ciprofloxacin [ 154 ], moxifloxacin hydrochloride [ 155 ], acetazolamide [ 136 ]; brimonidine for glaucoma therapy [ 144 ]; ganciclovir [ 156 ], indomethacin [ 133 ]; L-2-oxothiazolidine-4-carboxylic acid, which is involved in cataract treatment [ 157 ]; ketorolac tromethamine [ 138 , 142 , 145 ], bevacizumab [ 132 ], ranibizumab [ 158 ], celecoxib [ 159 ], doxorubicin [ 147 , 148 , 160 ], metronidazole [ 139 ]; dexamethasone [ 143 , 151 , 161 ], which is anti-inflammatory; bovine lactoferrin [ 150 ]; daptomycin for the treatment of bacterial endophthalmitis [ 129 ]; tobramycin sulfate [ 162 ], curcumin [ 146 ], rosmarinic acid [ 163 ], cardamom essential oil [ 164 ], and plant extracts [ 163 , 165 ]. Those NPs have been either administered as such or incorporated into other drug delivery formulations (see Chapter 3.4).…”