Travoprost Liquid Nanocrystals: An Innovative Armamentarium for Effective Glaucoma Therapy.

To date, the ophthalmic application of liquid crystalline nanostructures (LCNs) has not been thoroughly reconnoitered, yet they have been extensively used. LCNs are primarily made up of glyceryl monooleate (GMO) or phytantriol as a lipid, a stabilizing agent, and a penetration enhancer (PE). For optimization, the D-optimal design was exploited. A characterization using TEM and XRPD was conducted. Optimized LCNs were loaded with the anti-glaucoma drug Travoprost (TRAVO). Ex vivo permeation across the cornea, in vivo pharmacokinetics, and pharmacodynamic studies were performed along with ocular tolerability examinations. Optimized LCNs are constituted of GMO, Tween® 80 as a stabilizer, and either oleic acid or Captex® 8000 as PE at 25 mg each. TRAVO-LNCs, F-1-L and F-3-L, showed particle sizes of 216.20 ± 6.12 and 129.40 ± 11.73 nm, with EE% of 85.30 ± 4.29 and 82.54 ± 7.65%, respectively, revealing the highest drug permeation parameters. The bioavailability of both attained 106.1% and 322.82%, respectively, relative to the market product TRAVATAN®. They exhibited respective intraocular pressure reductions lasting for 48 and 72 h, compared to 36 h for TRAVATAN®. All LCNs exhibited no evidence of ocular injury in comparison to the control eye. The findings revealed the competence of TRAVO-tailored LCNs in glaucoma treatment and suggested the potential application of a novel platform in ocular delivery.

Cubosomal lipid nanoassemblies with pH-sensitive shells created by biopolymer complexes: A synchrotron SAXS study.

We report a strategy for sustainable development of pH-responsive cubic liquid crystalline nanoparticles (cubosomes), in which the structure-defining lyotropic nonlamellar lipid and the eventually encapsulated guest molecules can be protected by pH-sensitive polyelectrolyte shells with mucoadhesive properties. Bulk non-lamellar phases as well as pH-responsive polyelectrolyte-modified nanocarriers were formed by spontaneous assembly of the nonlamellar lipid monoolein and two biopolymers tailored in nanocomplexes with pH-dependent net charge. The mesophase particles involved positively charged N-arginine-modified chitosan (CHarg) and negatively charged alginate (ALG) chains assembled at different biopolymer concentrations and charge ratios into a series of pH-responsive complexes. The roles of Pluronic F127 as a dispersing agent and a stabilizer of the nanoscale dispersions were examined. Synchrotron small-angle X-ray scattering (SAXS) investigations were performed at several N-arginine-modified chitosan/alginate ratios (CHarg/ALG with 10, 15 and 20 wt% ALG relative to CHarg) and varying pH values mimicking the pH conditions of the gastrointestinal route. The structural parameters characterizing the inner cubic liquid crystalline organizations of the nanocarriers were determined as well as the particle sizes and stability on storage. The surface charge variations, influencing the measured zeta-potentials, evidenced the inclusion of the CHarg/ALG biopolymer complexes into the lipid nanoassemblies. The polyelectrolyte shells rendered the hybrid cubosome nanocarriers pH-sensitive and influenced the swelling of their lipid-phase core as revealed by the acquired SAXS patterns. The pH-responsiveness and the mucoadhesive features of the cubosomal lipid/polyelectrolyte nanocomplexes may be of interest for in vivo drug delivery applications.

Delineating penetration enhancer-enriched liquid crystalline nanostructures as novel platforms for improved ophthalmic delivery.

Liquid crystalline nanostructures (LCNs), for instance cubosomes, have been widely used as a promising carrier for drug delivery through the last few years. To date, the ophthalmic application of these platforms was not well explored, and the effect of integrating penetration enhancers (PEs) into LCNs has not been investigated yet. Hence, the present work aimed coupling novel PEs into glyceryl monooleate-based cubosomes for ocular administration. Various enhancers viz, free fatty acids (oleic and linoleic acids), natural terpenes (D-limonene and cineole), medium-chain triglycerides (Captex® 1000 and Captex® 8000), mono-/di-glycerides (Capmul® MCM, Capmul® PG-8, and Capmul® PG-12) were tested at different amounts. The morphology of the formed LCNs was investigated using transmission electron microscopy (TEM). The crystallinity and thermal behavior studies were also conducted. The ocular safety of optimized formulae was tested via hen's egg test-chorioallantoic membrane (HET-CAM), rabbit eye Draize test, and histopathological examinations of ocular tissues. Confocal laser scanning microscopy (CLSM) was utilized to assess the enhanced permeation of fluorescently-labeled LCNs across corneal layers. The acceptable formulations exhibited relatively homogenous particle nano-sizes ranging from 139.26 ± 3.68 to 590.56 ± 24.86 nm carrying negative surface charges. TEM images, X-ray patterns and DSC thermograms demonstrated the influential effect of PEs in developing altered crystalline structures. The ocular compatibility of optimized LCNs was confirmed. The corneal distribution using CLSM proved the disseminated fluorescence intensity of LCNs enriched with oleic acid, Captex® 8000 and Capmul® MCM. Selected LCNs showed good physical stability upon storage and lyophilization. The results demonstrated the efficiency of tailored PE-modified LCNs in enhancing the ocular transport with no evidence of any irritation potential, and hence suggested their prospective applicability in ophthalmic drug delivery.