Role of mucoadhesive agent in ocular delivery of ganciclovir microemulsion: cytotoxicity evaluation in vitro and ex vivo.

PURPOSE: The aim of the present study was to investigate increase in delivery of drug upon formulation as mucoadhesive microemulsion system and further to investigate possibility of any cytotoxic effects using such formulation. MATERIAL AND METHODS: Considering hydrophilic and small molecular nature of the drug, it was attempted to be formulated as microemulsion, by using pseudo ternary phase diagram method. Thus, three types of microemulsions were prepared; oil in water, water in oil type and chitosan-coated microemulsion. These microemulsions were characterized for several physicochemical properties like size, zeta potential, Polydispersity index, and compared for in vitro cell viability and ex vivo corneal irritation study. RESULTS: All three microemulsions were quite stable, transparent and homogenous systems. They showed similar drug release pattern, but highest ex vivo goat corneal permeation was observed with Chitosan coated microemulsion when compared with ganciclovir solution. CONCLUSION: All microemulsions were found to be non-irritant in in vitro cell viability assay and ex vivo corneal irritation study, indicating the potential of using such systems for delivery of drug to eye.

Triamcinolone Acetonide-Loaded PEGylated Microemulsion for the Posterior Segment of Eye.

Present work investigates the possibility of a polyethyleneglycolylated (PEGylated) microemulsion (ME) to deliver drug to the posterior segment of eye. Triamcinolone acetonide (TA), a widely used drug in intraocular diseases, was selected as the model drug. Based on solubility and emulsification capacity, components of microemulsion were selected and optimum formulation was obtained using a pseudoternary phase diagram. The optimized ratio of Capmul MCM C8 (oil): AccononMC8-2 (surfactant): Transcutol (cosurfactant): deionized water was 5:35.5:4.5:55. This was further PEGylated using 1,2-distearoylphosphatylethanolamine-polyethyleneglycol 2000 (DSPE-PEG 2000). This PEGylated ME loaded with TA was characterized and evaluated in vitro, ex vivo, and in vivo for topical ocular use. The developed PEGylated ME loaded with TA was homogenous, stable, and nonirritable to eye and had the ability to reach the posterior segment of eye on topical instillation.

PEGylated microemulsion for dexamethasone delivery to posterior segment of eye.

Dexamethasone (Dex) is one of the most commonly used anti-vascular endothelial growth factor (anti-VEGF) drugs being used in ocular diseases whether it is associated with anterior segment or posterior segment. For diseases of posterior segment of eye, Dex is delivered as intravitreal implant but the route used for the same is very invasive and poses several hazards on long term use. Thus, topical formulation with ability to outreach retina from ocular surface was intended. Thus, polyethylene glycolylated (PEGylated) microemulsion (ME) was attempted as it can cross the membranous barrier of eye (cornea, conjunctiva, and sclera) and remain afloat in fluidic barrier (aqueous humor, choroid, etc.) as well. Present investigation involved development of Dex-loaded PEGylated ME which was stable, non-toxic to ocular surface, capable to cross cornea and enhanced residence as well as availability of loaded drug in retina. The developed PEGylated ME had physicochemical properties like size (15.98 ± 3.05 nm), polydispersity index (0.25 ± 0.04), zeta potential (-0.04 ± 0.47 mV), percentage transmittance (99.84 ± 1.17%), and drug content (99.32 ± 3.21%). It showed sustained Dex release in in vitro conditions. It also displayed efficiency in enhancing retention of drugs in retina in in vivo pharmacokinetic study on Sprague-Dawley rats. PEGylated ME can retain the drug in retina of rats longer than simple eye drop solution via topical ocular route.

Exploring the potential of minoxidil tretinoin liposomal based hydrogel for topical delivery in the treatment of androgenic alopecia.

Purpose: Androgenic alopecia (AGA) is a condition of progressive hair loss and involves follicular miniaturization triggered mainly due to varying levels of androgen besides environmental and genetic factors, which may also play some role. Minoxidil (MXD) has been considered as most effective therapeutic moiety to treat this disorder. Another drug Tretinoin (TRET) is known for its comedolytic activity and is reported to enhance percutaneous absorption of MXD. Presently both these drugs are being utilized for treatment of androgenic alopecia (AGA) in solution form which poses several problems in terms of poor solubility of drug, frequency of application and side effects.Materials and methods: Current work investigates liposomal hydrogel system for simultaneous delivery of MXD and TRET to overcome the limitations of existing formulation. Successful development of liposomes was commenced by thin film hydration method and various parameters affecting desired characteristics like size, morphology, entrapment efficiency; stability and ex vivo permeation were optimized. The formulated liposomes were further characterized for various physicochemical properties and evaluated for in vivo irritancy study in animals.Results and discussion: Results suggested prepared liposomes to be stable, homogenous and capable to hold both the drugs within. Association with hydrogel enhanced the permeation of MXD through skin ex vivo but TRET retained on the skin. Liposome loaded hydrogel was found to be non-irritant to skin.Conclusion: Overall developed system showed potential for effective and simultaneous delivery of both the drugs.

Cow ghee fortified ocular topical microemulsion; in vitro, ex vivo, and in vivo evaluation.

Aim: Utility of cow ghee (CG) as permeation enhancer in development of topical ocular microemulsion (ME) for delivery of fluocinolone acetonide (FA) to posterior eye. Methods: For ME preparation, oil, surfactant and cosurfactant were screened based on solubility of FA. Pseudoternary phase diagrams were constructed to determine their ratios. The developed MEs were characterised for their physicochemical properties like size, polydispersity index, zeta potential, and stability etc. They were evaluated for ex vivo permeation and irritation. In vivo pharmacokinetic studies were performed on Sprague dawley rats. Results: Lauroglycol as oil, labrasol as surfactant and Transcutol as cosurfactant were selected. The optimised ratio of oil:surfactant:cosurfactant:water was 4:23:23:50. The developed FA loaded ME fortified with CG was characterised. Ex vivo study revealed higher permeation and non-irritancy. In vivo pharmacokinetic study showed retention of CG fortified ME in posterior rat eye. Conclusion: Present investigation established CG as permeation enhancer for ocular topical formulation.

A review on recent drug delivery systems for posterior segment of eye.

Eye is the unique sense organ with complex and sophisticated anatomy and physiology. Being most instrumental for vision, it is secured by varied protective barriers; ranging from static (membranous) to dynamic (vascular) barrier. Although these barriers are very efficient to protect eye from exogenous substances and external stress, it is caught by various irreversible vision impairing ailments like cataract, conjunctivitis, glaucoma, uveitis, diabetic retinopathy (DR), diabetic macular edema (DME), age related macular degeneration (AMD), cytomegalovirus (CMV) retinitis, retinitis pigmentosa (RP), retinal vein occlusion (RVO), endophthalmitis affecting both anterior and posterior segment of eye. The treatment needed to reach the site of action is restricted by its characteristic barriers. The protective mechanism turns into hurdles when it comes to drug delivery especially in case of posterior segment of eye. Most common and preferable routes for ocular drug delivery are topical and systemic routes owing to their compliance and non-invasive nature, however they turned inefficient in delivering drugs to posterior segment. Currently, other local routes like intraocular and periocular (subconjunctival, subtenon, posterior juxtascleral, retrobulbar, peribulbar) are being explored and are showing positive outcomes in terms of symptomatic relief for a certain time period. But as these are invasive techniques, they also have some hidden long-term drawbacks on other side. Various advancements have been achieved till date in delivery of drug to posterior segment of eye, however despite these advancements; there is need of non-invasive or preferably less invasive technique considering prolonged treatments for such ailments. At times, dependency on invasive techniques may cause problems like patient incompliance, inflammation, contact cataract, retinal detachment, endophthalmitis etc. Here, in this review, barriers in ocular delivery, routes and recent advances in drug delivery to eye including patented commercial formulations with emphasis on posterior segment will be discussed.

Coenzyme Q10 and retinaldehyde co-loaded nanostructured lipid carriers for efficacy evaluation in wrinkles.

This study depicts coenzyme Q10 (CoQ10) and retinaldehyde (RAL) co-loaded nanostructured lipid carriers (NLCs); having activity on different targets of photoageing, which can overcome deficits of conventional topical dosage forms. The developed NLCs were characterised for particle size, polydispersity index and percent entrapment efficiency (%EE), followed by their incorporation into Carbopol® 934 P-NF gel. In vitro cellular uptake and cytotoxicity assay was performed to evaluate NLCs and in vivo study on ultraviolet- (UV) induced wrinkle model to determine efficacy of NLCs. The developed stable, homogenous and spherical NLCs with size range of 200-230 nm and more than 80 %EE, showed prolonged, biphasic in vitro release pattern for CoQ10 and RAL. Ex vivo study portrayed negligible permeation through skin but appreciable penetration and distribution in skin layers. This has shown good uptake of both drugs with least cytotoxicity in cell culture studies. In vivo irritation study on Sprague Dawley (SD) rats and pharmacodynamic study on female Swiss albino mice proved it less irritant and efficacious. The developed NLCs thus hold promise in the efficient management of wrinkle and their reduction as indicated by the data obtained.

Novel nanosystems for the treatment of ocular inflammation: Current paradigms and future research directions.

Ocular discomforts involve anterior/posterior-segment diseases, symptomatic distress and associated inflammations and severe retinal disorders. Conventionally, the formulations such as eye drops, eye solutions, eye ointments and lotions, etc. were used as modalities to attain relief from such ocular discomforts. However, eye allows limited access to these traditional formulations due to its unique anatomical structure and dynamic ocular environment and therefore calls for improvement in disease intervention. To address these challenges, development of nanotechnology based nanomedicines and novel nanosystems (liposomes, cubosomes, polymeric and lipidic nanoparticles, nanoemulsions, spanlastics and nano micelles) are currently in progress (some of them are already marketed such as Eye-logic liposomal eye spray@Naturalife, Ireland). Today, it is one of the central concept in designing more accessible formulations for deeper segments of the eyes. These nanosystems has largely enabled the availability of medicaments at required site in a required concentration without inversely affecting the eye tissues; and therefore, attaining the excessive considerations from the formulation scientists and pharmacologists worldwide. The entrapment of drugs, genes, and proteins inside these novel systems is the basis that works at the bio-molecular level bestows greater potential to eradicate disease causatives. In this review, we highlighted the recent attempts of nanotechnology-based systems for treating and managing various ocular ailments. The progress described herein may pave the way to new, highly effective and vital ocular nanosystems.