Development and validation of high-performance liquid chromatography method for the simultaneous quantification of rivastigmine hydrogen tartrate and asiaticoside co-loaded in niosomes: A Box-Behnken design approach.

Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, is considered as the first-line therapy for mild to moderate Alzheimer's disease. Asiaticoside (AS), a pentacyclic triterpenoid saponin, is well known as cognitive enhancer due to its antioxidant effect. Based on the hypothesis of their synergistic therapeutic potential, RHT and AS were co-encapsulated in niosomal formulation. A simple, precise, and accurate high-performance liquid chromatography method was developed for simultaneous quantitative analysis. The chromatographic parameters were optimized by Box-Behnken experimental design. The separation was performed on a reversed-phase Phenomenex C18 (150 mm × 4.6 mm, 5 µm) column at 30 °C under the UV detection of 210 nm. The optimized mobile phase consisted of a mixture of 20 mM potassium dihydrogen phosphate buffer (pH 2.6) and acetonitrile (72:28 % v/v) under the isocratic mode at the flow rate of 0.9 mL/min. The developed method was fully validated under the ICH guidelines and could be successfully applied for simultaneous quantitative analysis of RHT and AS in niosomal formulation.

Celecoxib/Cyclodextrin Eye Drop Microsuspensions: Evaluation of In Vitro Cytotoxicity and Anti-VEGF Efficacy for Retinal Diseases.

Celecoxib (CCB), a cyclooxygenase-2 inhibitor, is capable of reducing oxidative stress and vascular endothelial growth factor (VEGF) expression in retinal cells and has been shown to be effective in the treatment of diabetic retinopathy and age-related macular degeneration. However, the ocular bioavailability of CCB is hampered due to its very low aqueous solubility. In a previous study, we developed 0.5% (w/v) aqueous CCB eye drop microsuspensions (MS) containing randomly methylated ß-cyclodextrin (RMßCD) or γ-cyclodextrin (γCD) and hyaluronic acid (HA) as ternary CCB/CD/HA nanoaggregates. Both formulations exhibited good physicochemical properties. Therefore, we further investigated their cytotoxicity and efficacy in a human retina cell line in this study. At a CCB concentration of 1000 µg/mL, both CCB/RMßCD and CCB/γCD eye drop MS showed low hemolysis activity (11.1 ± 0.3% or 4.9 ± 0.2%, respectively). They revealed no signs of causing irritation and were nontoxic to retinal pigment epithelial cells. Moreover, the CCB eye drop MS exhibited significant anti-VEGF activity by reducing VEGF mRNA and protein levels compared to CCB suspended in phosphate buffer saline. The ex vivo transscleral diffusion demonstrated that a high quantity of CCB (112.47 ± 37.27 µg/mL) from CCB/γCD eye drop MS was deposited in the porcine sclera. Our new findings suggest that CCB/CD eye drop MS could be safely delivered to the ocular tissues and demonstrate promising eye drop formulations for retinal disease treatment.

Physicochemical and Stability Evaluation of Topical Niosomal Encapsulating Fosinopril/γ-Cyclodextrin Complex for Ocular Delivery.

This study aimed to develop a chemically stable niosomal eye drop containing fosinopril (FOS) for lowering intraocular pressure. The effects of cyclodextrin (CD), surfactant types and membrane stabilizer/charged inducers on physiochemical and chemical properties of niosome were evaluated. The pH value, average particle size, size distribution and zeta potentials were within the acceptable range. All niosomal formulations were shown to be slightly hypertonic with low viscosity. Span® 60/dicetyl phosphate niosomes in the presence and absence of γCD were selected as the optimum formulations according to their high %entrapment efficiency and negative zeta potential values as well as controlled release profile. According to ex vivo permeation study, the obtained lowest flux and apparent permeability coefficient values confirmed that FOS/γCD complex was encapsulated within the inner aqueous core of niosome and could be able to protect FOS from its hydrolytic degradation. The in vitro cytotoxicity revealed that niosome entrapped FOS or FOS/γCD formulations were moderate irritation to the eyes. Furthermore, FOS-loaded niosomal preparations exhibited good physical and chemical stabilities especially of those in the presence of γCD, for at least three months under the storage condition of 2-8 °C.

Cyclodextrin-based formulation of carbonic anhydrase inhibitors for ocular delivery - A review.

Carbonic anhydrase inhibitors (CAIs) are used as systemic and topical agents for lowering intraocular pressure (IOP) in patients with glaucoma. Owing to the wide distribution of CAs and their physiological functions in various tissues, systemic administration of CAIs may lead to unwanted side effects. Thus, exploration of drugs targeting the specific CA isoenzyme in ocular tissues and application of the same as topical eye drops would be desirable. However, the anatomical and physiological barriers of the eyes can limit drug availability at the site. The very low aqueous solubility of CAI agents can further hamper drug bioavailability, consequently resulting in insufficient therapeutic efficacy. Solubilization of drugs using cyclodextrin (CD) complexes can enhance both solubility and permeability of the drugs. The use of CD for such purposes and development and testing of topical CAI eye drops containing CD have been discussed in detail. Further, pharmaceutical nanotechnology platforms were discussed in terms of investigation of their IOP-lowering efficacies. Future prospects in drug discovery and the use of CD nanoparticles and CD-based nanocarriers to develop potential topical CAI formulations have also been described here.