Oil-free eye drops containing Cyclosporine A/cyclodextrin/PVA supramolecular complex as a treatment modality for dry eye disease.

According to the global mapping of dry eye disease (DED), nearly 5 to 50 % of people suffer from DED, and this number is on the rise. The drug of choice Cyclosporine A (CsA) exhibits poor ocular bioavailability due to high molecular weight and lipophilicity. Moreover, formulations of CsA currently available are in the form of oil-based emulsions that are known to cause ocular irritation and pain. In this study, sulfobutylether-ß-cyclodextrin (SBE-ß-CD) based binary and ternary supramolecular complexes of CsA were developed as completely oil-free, and particle-free eye drops to treat DED. The physicochemical characterizations were supplemented with relevant in silico studies, to ascertain the findings. Further, the efficacy of the complexes was evaluated in the scopolamine-induced mouse model of DED. The complexation improved the CsA solubility by ~21-fold, with ~4-fold improvement in dissolution and transcorneal permeation. The non-irritancy and non-toxicity were confirmed by hen's egg chorioallantoic membrane assay and cytotoxicity assay using human corneal epithelial cells, respectively. The in vivo treatment with the ternary CD complex demonstrated better management of the dry eye supported by the tear volume assessment, corneal fluorescein staining, and histopathological studies of the cornea, lacrimal gland, and harderian gland. The study demonstrates the potential of the supramolecular complex as an alternative to the oil-based formulation of eye drops for drugs that show low solubility and poor corneal permeation.

Colloidal nanostructured lipid carriers of pentoxifylline produced by microwave irradiation ameliorates imiquimod-induced psoriasis in mice.

Psoriasis is a chronic inflammatory disease occurring due to a large cascade of molecular and biological processes. Pentoxifylline (PTX) has a profound anti-inflammatory activity and is clinically indicated in the management of psoriasis. PTX is highly hydrophilic and thus is permeation-limited to exert its action on the psoriatic lesions. Colloidal nanostructured lipid carriers (NLCs) is a boon for dermal drug delivery, but incorporation of hydrophilic medicaments is not only difficult to be achieved but is accompanied by suboptimal loading, erratic drug release and time-consuming. The present study was designed to develop NLCs incorporating PTX using the recently explored thin lipid film based microwave assisted rapid technique. Prior to the formulation, the crystal structure of PTX was analyzed by molecular modeling. NLCs formed within 4 min having a size of <200 nm, PDI of <0.250 and a surface charge <-28 mV. PTX was loaded and encapsulated to an extent of 10% and 90% in the NLCs. The drug flux was 4.848 µg/cm2/h at the end of 24 h with a detection of 14% in the receptor fluid indicating a higher retention of PTX within the skin (>84%). In addition, the PTX loaded NLCs were tested against imiquimod-induced psoriasis in mouse model. Histological examinations clearly showed a higher levels of remodeling of the skin layers compared to disease control. These results justify NLCs to be a promising topical delivery system for PTX during psoriasis and can be rapidly produced without the requirement of complex equipment and conditions.

Pectin-based silver nanocomposite film for transdermal delivery of Donepezil.

A novel pectin-based silver nanocomposite film has been synthesized with the aid of microwave, using green technology and its capacity to adsorb and deliver anti-Alzheimer's drug Donepezil (DPZ) has been investigated. The nanocomposite exhibited excellent adsorption and release efficiency. The pristine and the drug loaded films were characterized using FTIR, TGA, XRD and FESEM-EDS techniques. The DPZ release capacity of the nanocomposite in phosphate buffer saline solution was found to be 94.33 ±â€¯2.12% during 5 days period. Along with the drug, about 92 kcps silver nanoparticles were observed to be released from the film leading to enhanced activity of the system. The drug release followed zero order kinetics and non-Fickian type of diffusion. Toxicity studies of the nanocomposite film conducted with sheep erythrocytes showed <9% hemolysis indicating the non-toxic and blood compatible nature. Further, the antimicrobial activity of the nanocomposite film against S. aureus and E. coli was quite significant compared to the standard antibiotics. These results reveal the nanocomposite film to be appropriate for the transdermal application avoiding the contamination due to the continuous contact of sweat and moisture from the skin.

Development of MART for the Rapid Production of Nanostructured Lipid Carriers Loaded with All-Trans Retinoic Acid for Dermal Delivery.

All-trans retinoic acid (ATRA) has been regarded as a wonder drug for many dermatological complications; however, its application is limited due to the extreme irritation, and toxicity seen once it has sufficiently concentrated into the bloodstream from the skin. Thus, the present study was aimed to increase the entrapment of ATRA and minimize its transdermal permeation. ATRA incorporated within nanostructured lipid carriers (NLCs) were produced by a green and facile thin lipid-film based microwave-assisted rapid technique (MART). The optimization was carried out using the response surface methodology (RSM)-driven artificial neural network (ANN) coupled with genetic algorithm (GA). The liquid lipid and surfactants were seen to play a very crucial role culminating in the particle size (< 70 nm), zeta potential (< - 32 mV), and entrapment of ATRA (> 98%). ANN-GA-optimized NLCs required a minimal quantity of the surfactants, formed within 2 min and were stable for 1 year at different storage conditions. The optimized NLC-loaded creams showed a skin retention (ex vivo) to an extent of 87.42% with no detectable drug in the receptor fluid (24 h) in comparison to the marketed cream which released 47.32% (12 h) of ATRA. The results were in good correlation with the in vivo skin deposition studies. The NLCs were biocompatible and non-skin irritant based on the primary irritation index. In conclusion, the NLCs were seen to have a very high potential in overcoming the drawbacks of ATRA for dermal delivery and could be produced conveniently by the MART.

Application of pectin­zinc oxide hybrid nanocomposite in the delivery of a hydrophilic drug and a study of its isotherm, kinetics and release mechanism.

Pectin-based gel and its nanocomposite with zinc oxide have been compared for their capacity to release Donepezil for the possible use as an implantable drug delivery platform for the treatment of Alzheimer's disease. Adsorption capacities of the samples were determined as a function of pH, temperatures, concentrations of the drug, and the mass of the adsorbent. The nanocomposite exhibited significant adsorption compared to the parent gel. Adsorption data for the nanocomposite system fits well with Langmuir model and followed pseudo-first order kinetics, while that of the parent polymeric system followed pseudo-second-order kinetics. Donepezil adsorbed polymeric samples were prepared and evaluated for tensile strength, swelling index, folding endurance and characterized by FTIR, FESEM, EDS, XRD and TGA techniques. The desorption of zinc oxide was also monitored using the dynamic light scattering technique. The in vitro drug release study indicated desorption of Donepezil to the maximum extent of ~88% and 46% during 5 days period from the nanocomposite and the parent gel respectively. The developed systems showed negligible (<10%) percentage of hemolysis after incubation with sheep erythrocytes. In conclusion, the developed pectin-based nanocomposite can be explored as a potential platform for the development of implantable drug delivery systems for chronic diseases.