Spermidine as an epigenetic regulator of autophagy in neurodegenerative disorders.

Autophagy is an abnormal protein degradation and recycling process that is impaired in various neurological diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease. Spermidine is a natural polyamine found in various plant- and meat-based diets that can induce autophagy, and is decreased in various neurodegenerative diseases. It acts on epigenetic enzymes like E1A-binding protein p300, HAT enzymes like Iki3p and Sas3p, and α-tubulin acetyltransferase 1 that modulate autophagy. Histone modifications like acetylation, phosphorylation, and methylation could influence autophagy. Autophagy is epigenetically regulated in various neurodegenerative disorders with many epigenetic enzymes and miRNAs. Polyamine regulation plays an essential role in the disease pathogenesis of AD and PD. Therefore, in this review, we discuss various enzymes and miRNAs involved in the epigenetic regulation of autophagy in neurodegenerative disorders and the role of spermidine as an autophagy enhancer. The alterations in spermidine-mediated regulation of Beclin-1, LC3-II, and p62 genes in AD and other PD-associated enzymes could impact the process of autophagy in these neurodegenerative diseases. With the ever-growing data and such promising effects of spermidine in autophagy, we feel it could be a promising target in this area and worth further detailed studies.

Curcumin-sulfobutyl-ether beta cyclodextrin inclusion complex: preparation, spectral characterization, molecular modeling, and antimicrobial activity.

Urinary tract infections (UTIs) caused by Gram-negative bacteria E. coli is responsible for 80-90% of uncomplicated cases in women. The increased prevalence of antibiotic resistance has made the management of UTIs more challenging. Plant-derived compounds have long been used to treat various diseases, and constitute an alternative to antibiotic resistance. Curcumin (CUR), a naturally occurring polyphenolic phytoconstituent obtained from Curcuma longa is endowed with diverse medicinal properties. The present study aims to form a complex of CUR with Sulfobutyl ether-ß-cyclodextrin (SBEßCD) to overcome the poor solubility and bioavailability of CUR and to evaluate the antimicrobial activity of CUR-SBEßCD. Phase solubility studies and spectral characterization showed the entrapment of CUR in the SBEßCD cavity. In silico docking studies performed to investigate the complexation process of CUR with SBEßCD, revealed that the methoxy group and OH group of CUR interacted with SBEßCD. The cytotoxicity and HET-CAM assays confirmed that CUR-SBEßCD was non-irritant. The prepared complex investigated with the disc diffusion method showed antimicrobial activity with a zone of inhibition (ZOI) of 13 mm against Escherichia coli (E. coli) and 11.5 mm against Staphylococcus aureus (S. aureus) whereas CUR alone did not show any ZOI. It can be concluded that prepared CUR-SBEßCD demonstrated superior antimicrobial activity and therefore can be a promising alternative for the treatment of UTIs.Communicated by Ramaswamy H. Sarma.

Natamycin Ocular Delivery: Challenges and Advancements in Ocular Therapeutics.

Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics.

Rodent models for dry eye syndrome: Standardization using benzalkonium chloride and scopolamine hydrobromide.

Dry eye disease is a highly prevalent ocular condition that significantly affects the quality of life and presents a major challenge in ophthalmology. Animal models play a crucial role in investigating the pathophysiology and developing effective treatments. The goal of this study was to compare and standardize two dry eye disease rodent models and explore their recovery aspects. We have standardized benzalkonium chloride and scopolamine-induced dry eye disease models which represents two different classes of the dry eye i.e., evaporative dry eye and aqueous deficient dry eye, respectively. After the development of dry eye conditions, a self-recovery period of seven days was granted to assess the reversal of the induced changes. The dry eye condition was assessed by measuring tear volume, corneal slit lamp imaging, and histological examination of the cornea, the lacrimal and the harderian gland. The study indicated the development of chronic inflammation of the cornea and lacrimal gland in the case of benzalkonium after five days of the treatment, while the scopolamine treated group showed chronic inflammation of the lacrimal gland after five days and corneal inflammation after seven days of administration. The recovery study suggested that after discontinuation of inducing agent, the dry eye symptoms were still persistent suggesting the utility of the model in evaluating dry eye treatments. The study highlights the comparative changes in both models along with recovery which can serve as a base for drug discovery and development against dry eye disease.

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.

Cyclodextrin-Based Supramolecular Ternary Complexes: Emerging Role of Ternary Agents on Drug Solubility, Stability, and Bioavailability.

The aqueous solubility of active drug moiety plays a crucial role in the development of an efficacious formulation. The poor aqueous solubility of BCS class II and IV drugs is manifested as poor bioavailability. Preparation of cyclodextrin inclusion complex to improve the solubility, stability, and bioavailability is a well-established technique. The latest trend in cyclodextrin research is focused on ternary complexes wherein an auxiliary agent such as water-soluble polymers, organic ions, metals, or amino acids is incorporated in the inclusion complex. The cyclodextrin-based supramolecular ternary complex offers significant advantages over binary complex specifically for oral drug delivery. Compared with the binary complex, the ternary complex exhibits better complexation efficiency and stability constant. Moreover, the ternary complex has a major advantage of reducing the concentration of cyclodextrin required to achieve maximum solubility and stability. Lately, in silico molecular modeling has gained tremendous attention as a preliminary tool to evaluate the cyclodextrin-based ternary or binary complex which has been discussed. This review gives an insight into various ternary agents explored worldwide, significant observations, safety, and clinical studies carried out on ternary cyclodextrin complexes.

A Sensitive Spectrofluorimetric Method for Curcumin Analysis.

Curcumin (CUR), a natural polyphenolic compound extracted from the rhizomes of Curcuma longa, is used as a pharmaceutical agent, spice in food, and as a dye. Currently, CUR is being investigated for cancer treatment in Phase-II clinical trials. CUR also possesses excellent activities like anti-inflammatory, anti-microbial, and anti-oxidant, therefore quality control is crucial. The present research work was to develop a new, simple, validated and time-saving rapid 96-well plate spectrofluorimetric method for the determination of CUR. The developed method was compared with routinely used high performance liquid chromatography (HPLC) technique. The developed method were found to be linear in the concentration range of 15 to 3900 ng/mL with R2 ≥ 0.9983 for spectrofluorimetric and 50-7500 ng/mL with R2 ≥ 0.9999 for HPLC method. Accuracy, intraday and interday precision was adequate, with RSD lower than the suggested limits. The limits for the detection and the quantification of CUR were 7 and 15 ng/mL for spectrofluorimetric, and 25 and 50 ng/mL for HPLC respectively. The Bland-Altman analysis demonstrated the similarities between the two methods. The 96-well plate method was successfully applied to determine CUR in solid lipid nanoparticles (SLNs) and chitosan nanoparticles (Chi-NPs). The developed spectrofluorimetric method can hence serve as a possible replacement for the HPLC method for the quantification of CUR in healthcare and food products.

A supramolecular thermosensitive gel of ketoconazole for ocular applications: In silico, in vitro, and ex vivo studies.

The incidence of corneal fungal infections continues to be a growing concern worldwide. Ocular delivery of anti-fungal drugs is challenging due to the anatomical and physiological barriers of the eye. The ocular bioavailability of ketoconazole (KTZ), a widely prescribed antifungal agent, is hampered by its limited aqueous solubility and permeation. In the study, the physicochemical properties of KTZ were improved by complexation with sulfobutylether-ß-cyclodextrin (SBE-ß-CD).KTZ-SBE-ß-CD complex was studied in silico with docking and dynamics simulations, followed by wet-lab experiments.The optimized KTZ-SBE-ß-CD complex was loaded into a thermosensitivein situ gel to increase corneal bioavailability. The supramolecular complex increased the solubility of KTZ by 5-folds and exhibited a 10-fold increment in drug release compared to the pure KTZ. Owing to the diffusion, thein situ gel exhibited a more sustained drug release profile. Theex vivocorneal permeation studies showed higher permeation from KTZ-SBE-ß-CD in situ gel (flux of ∼19.11 µg/cm2/h) than KTZin situ gel (flux of ∼1.17 µg/cm2/h). The cytotoxicity assays and the hen's egg chorioallantoic membrane assay (HET-CAM) confirmed the formulations' safety and non-irritancy. In silico guided design of KTZ-SBE-ß-CD inclusion complexes successfully modified the physicochemical properties of KTZ. In addition, the loading of the KTZ-SBE-ß-CD complex into an in situ gel significantly increased the precorneal retention and permeation of KTZ, indicating that the developed formulation is a viable modality to treat fungal keratitis.

Derma roller mediated transdermal delivery of tizanidine invasomes for the management of skeletal muscle spasms.

Tizanidine hydrochloride (TIZ) is a skeletal muscle relaxant used to treat spasms, a sudden involuntary muscle contraction. The currently available oral dosage forms exhibit low oral bioavailability due to high first-pass metabolism. Frequent administration of the drug is thus necessary because of the short half-life of the drug. Transdermal delivery is an excellent alternative, but the skin's outer stratum corneum barrier prevents most drugs from being effectively delivered into the bloodstream. Here we present a pre-clinical investigation of derma roller mediated delivery of TIZ invasome gel as a potential approach for treating muscle spasm. Further, specific terpenes namely limonene and pinene in different concentrations and their impact on the properties of the prepared TIZ invasomes, including particle size, drug entrapment, and ex vivo drug release, were investigated. TIZ invasomes were incorporated into a gel and delivered to rats with and without pre-treatment of the skin with a derma roller. Pre-treated skin achieved maximum drug plasma concentrations within 3 ± 0.00 h of gel application and maintained for 24 h. In the untreated skin the maximum plasma drug levels was achieved at the end of 6 ± 0.00 h. The findings were further supported by in vivo efficacy studies conducted using rotarod and actophotometer. Overall, the study indicates that derma roller mediated transdermal delivery of TIZ loaded invasomes is a promising strategy for enhancing the bioavailability of TIZ.

Next-generation contact lenses: Towards bioresponsive drug delivery and smart technologies in ocular therapeutics.

In contrast to the conventional ocular formulations, contact lenses are well known for their diverse applications ranging from bio-sensing, prevention of myopia, cosmetics, and drug delivery. With a tremendous change in the lifestyle, contact lenses for therapeutic purposes have increased several fold. Contact lenses as medicated lenses suffer from several disadvantages, and to overcome the same numerous approaches have been explored. Researches worldwide have come a long way from cyclodextrin-based and vitamin E-based modified contact lenses to bioinspired approaches to enhance the effectiveness of the drug-eluting contact lenses. The bioinspired approach exploits bioinspired polymeric systems to enhance biocompatibility, specific molecule recognition technique by molecular imprinting, or stimuli-responsive system to improve the biocompatibility, drug loading, and drug delivery efficacy of the drug-eluting contact lenses. Moreover, recent innovations in ocular therapeutics such as nanowafers and microneedle contact lenses, and ocular patches have gained tremendous attention in ocular therapeutics. Another potential application of the contact lenses are smart lenses applied in the biosensing and diagnosis of various ocular disorders. The review summarizes and discusses the widespread therapeutic applications of next-generation contact lenses and various fabrication approaches, including its clinical implications, efforts taken by researchers in exploring the novel materials and diverse forms of the lenses, mechanisms of drug release, clinical trials, and their toxicity and safety concerns.

Small interfering RNAs (siRNAs) based gene silencing strategies for the treatment of glaucoma: Recent advancements and future perspectives.

RNA-interference-based mechanisms, especially the use of small interfering RNAs (siRNAs), have been under investigation for the treatment of several ailments and have shown promising results for ocular diseases including glaucoma. The eye, being a confined compartment, serves as a good target for the delivery of siRNAs. This review focuses on siRNA-based strategies for gene silencing to treat glaucoma. We have discussed the ocular structures and barriers to gene therapy (tear film, corneal, conjunctival, vitreous, and blood ocular barriers), methods of administration for ocular gene delivery (topical instillation, periocular, intracameral, intravitreal, subretinal, and suprachoroidal routes) and various viral and non-viral vectors in siRNA-based therapy for glaucoma. The components and mechanism of siRNA-based gene silencing have been mentioned briefly followed by the basic strategies and challenges faced during siRNA therapeutics development. We have emphasized different therapeutic targets for glaucoma which have been under research by scientists and the current siRNA-based drugs used in glaucoma treatment. We also mention briefly strategies for siRNA-based treatment after glaucoma surgery.

Derma rollers in therapy: the transition from cosmetics to transdermal drug delivery.

Derma roller, a device rolled onto the skin to form micropores, is extensively used for cosmetic purposes. The pores thus created are utilized to either result in the induction of collagen production, leading to glowing and wrinkle-free skin or for permeating the applied formulations to the site of action within the skin. Recent studies have shown the benefits of using derma rollers for transdermal delivery of drugs. In the nascent stage, this approach paves a way to successfully breach the stratum corneum and aid in the movement of medications directed towards the dermis and the hair follicles. The review essentially summarizes the evidence of the use of derma rollers in cosmetic setup, their designing, and the preclinical and clinical reports of efficacy, safety, and concerns when translated for pharmaceutical purposes and transdermal drug delivery.

Lipid vesicles: A versatile drug delivery platform for dermal and transdermal applications.

Topical and transdermal application of active pharmaceutical ingredients to the skin is an attractive strategy being explored by formulation scientists to treat disease conditions rather than the oral drug delivery. Several approaches have been attempted, and many of them have emerged with significant clinical potential. However, the delivery of drugs across the skin is an arduous task due to permeation limiting barriers. It, therefore, requires the aid of external agents or carrier systems for efficient permeation. Lipid-based vesicular systems are carriers for the transport of drugs through the stratum corneum (dermal drug delivery) and into the bloodstream for systemic action (transdermal drug delivery) overcoming the barrier properties. This review article describes the various vesicular systems reported for skin delivery of actives with relevant case studies. The vesicular systems presented here are in the order of their advent from conventional systems to the advanced lipid vesicles. The design and development of drugs in vesicular systems have brought a new dimension to the treatment of disease conditions overcoming the permeation limiting barriers, thus improving its efficacy.

Luliconazole-loaded nanostructured lipid carriers for topical treatment of superficial Tinea infections.

Tinea are superficial fungal infections caused by dermatophytes. Luliconazole exhibits highest antifungal activity against Trichophyton spp. which are major causative agents of dermatophytosis. However, luliconazole suffers from drawbacks such as less skin retention, low aqueous solubility and poor skin penetration. To overcome the limitations of luliconazole, nanostructured lipid carriers (NLCs) were formulated. NLCs are better permeation enhancers as they increase skin occlusion and hydration. The selection of various lipids and surfactants was based on the solubility of luliconazole in these components. Luliconazole NLC dispersion was prepared by hot melt emulsification technique followed by probe sonication. The dispersion was incorporated into a gel composed of Sepineo P 600 under magnetic stirring. in vitro antifungal studies were carried out with optimized luliconazole NLC gel, marketed luliconazole cream and control (luliconazole in gel base) against pathogenic Trichophyton rubrum. Ex-vivo diffusion study demonstrated that NLCs incorporated into gel exhibited greater retention on skin. In-vivo skin irritancy study showed no signs of erythema or edema post 24, 48, and 72 h at site of application. In comparison with marketed cream and based on the zone of inhibition diameters, NLC formulation was found to be very effective against Trichophyton rubrum.

Neuroprotection: A versatile approach to combat glaucoma.

In most retinal diseases, neuronal loss is the main cause of vision loss. Neuroprotection is the alteration of neurons and/or their environment to encourage the survival and function of the neurons, especially in environments that are deleterious to the neuronal health. The area of neuroprotection progresses with a therapeutically-based hope of improving vision and clinical outcomes for patients through the developments in neurotrophic therapy, antioxidative therapy, anti-excitotoxic, anti-ischemic, anti-inflammatory, and anti-apoptotic care. In this review, we summarize the various neuroprotection strategies for the treatment of glaucoma, genetics of glaucoma and the role of various nanoplatforms in the treatment of glaucoma.

Improved Oral Pharmacokinetics of Pentoxifylline with Palm Oil and Capmul® MCM Containing Self-Nano-Emulsifying Drug Delivery System.

Pentoxifylline (PTX), an anti-hemorrhage drug used in the treatment of intermittent claudication, is extensively metabolized by the liver resulting in a reduction of the therapeutic levels within a short duration of time. Self-nano-emulsifying drug delivery system (SNEDDS) is well reported to enhance the bio-absorption of drugs by forming nano-sized globules upon contact with the biological fluids after oral administration. The present study aimed to formulate, characterize, and improve the oral bioavailability of PTX using SNEDDS. The formulated SNEDDS consisted of palm oil, Capmul® MCM, and Tween® 80 as oil, surfactant, and co-surfactant, respectively. The mixture design module under the umbrella of the design of experiments was used for the optimization of SNEDDS. The dynamic light-scattering technique was used to confirm the formation of nanoemulsion based on the globule size, in addition to the turbidity measurements. In vivo bioavailability studies were carried out on male Wistar rats. The pharmacokinetic parameters upon oral administration were calculated using the GastroPlus software. The optimized SNEDDS had a mean globule size of 165 nm with minimal turbidity in an aqueous medium. Bioavailability of PTX increased 1.5-folds (AUC = 1013.30 ng h/mL) as SNEDDS than the pure drug with an AUC of 673.10 ng h/mL. In conclusion, SNEDDS was seen to enhance the bioavailability of PTX and can be explored to effectively control the incidents of intermittent claudication.

The Significance of Utilizing In Vitro Transfer Model and Media Selection to Study the Dissolution Performance of Weak Ionizable Bases: Investigation Using Saquinavir as a Model Drug.

This study investigated the dissolution behavior of BCS class II ionizable weak base Saquinavir and its mesylate salt in the multi-compartment transfer setup employing different composition of dissolution media. The dissolution behavior of Saquinavir was studied by using a two-compartment transfer model representing the transfer of drug from the stomach (donor compartment) to the upper intestine (acceptor compartment). Various buffers like phosphate, bicarbonate, FaSSIF, and FeSSIF were employed. The dissolution was also studied in the concomitant presence of the additional solute, i.e., Quercetin. Further, the dissolution profiles of Saquinavir and its mesylate salt were simulated by GastroPlusTM, and the simulated dissolution profiles were compared against the experimental ones. The formation of in situ HCl salt and water-soluble amorphous phosphate aggregates was confirmed in the donor and acceptor compartments of the transfer setup, respectively. As the consequence of the lower solubility product of HCl salt of Saquinavir, the solubility advantage of mesylate salt was vanished leading to the lower than the predicted dissolution in the acceptor compartment. However, the formation of water-soluble aggregates in the presence of the phosphate salts was observed leading to the higher than the predicted dissolution of the free base in the transfer setup. Interestingly, the formation of such water-soluble aggregates was found to be hindered in the concomitant presence of an ionic solute resulting in the lower dissolution rates. The in situ generation of salts and aggregates in the transfer model lead to the inconsistent prediction of dissolution profiles by GastroPlusTM.

Development and Investigation of Vitamin C-Enriched Adapalene-Loaded Transfersome Gel: a Collegial Approach for the Treatment of Acne Vulgaris.

Adapalene-loaded transfersome gel containing vitamin C as a combination therapy for the management of acne vulgaris was developed in the present study. The transfersome was prepared by reverse-phase evaporation, and the effect of various process parameters were investigated by the Design of Experiment (DOE) approach and optimized based on the particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The selected tranfersomes were further evaluated for their thermal behavior and morphology by transmission electron microscopy and turbidity measurements and incorporated into a gel with/without vitamin C. The gel was evaluated and compared with the marketed product (Adiff gel) for various physicochemical parameters, and in vivo studies in testosterone-induced rat models of acne. The prepared transfersomes had PS in the range of 280 to 400 nm, PDI values of 0.416 to 0.8, ZP of - 38 to - 20 mV, and % EE of 32 to 70%. DSC studies confirmed a positive interaction of the components in the transfersome. Surface morphology confirmed that the vesicles were spherical, unilamellar, and discrete. A relative deformability study showed higher elasticity of the transfersomes compared with Adiff aqs gel. Ascorbyl-6-palmitate in adapalene-loaded transfersome gel containing vitamin C (ADVTG) was found to have a good antioxidant free radical-scavenging activity. An in vitro drug release study showed that the sustained release of the transfersomal formulations was attributed to the flexibility of the vesicles by which penetration was increased. ADVTG was found to be promising in treating acne compared with the marketed product. Graphical Abstract.

Investigation of drug-polymer miscibility, biorelevant dissolution, and bioavailability improvement of Dolutegravir-polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer solid dispersions.

The aim of the current study was to prepare the efficacious amorphous solid dispersion of poorly water-soluble compound, Dolutegravir. After theoretical and experimental determination of drug-polymer miscibility, polyvinyl caprolactam-polyvinyl acetate-polyethylne glycol graft copolymer was chosen as a polymer. The solid dispersions of Dolutegravir were prepared by quench cooling and solvent evaporation method. Though quench cooling successfully stabilized the drug into amorphous form, solvent evaporation technique failed to render the drug completely amorphous. Owing to the negative Gibbs free energy at room temperature, the prepared dispersions were found stable at room temperature for 60 days. To resolve the overlapping contribution of micellar solubilization and amorphicity in improving the dissolution characteristics of Dolutegravir, the in vitro dissolution studies were performed in USP phosphate buffer as well as bio-relevant media. The dissolution advantage between prepared dispersions and pure drug in USP phosphate buffer was found bridged in the bio-relevant media. For this, the micellar solubilization driven dissolution of Dolutegravir in the presence of bile and lecithin micelles was thought as a contributing factor. Nevertheless, the dissolution advantage of dispersions prepared by quench cooling method was found endured in FeSSIF, which was thought to be due to its amorphicity leading to molecular level dissolution. Subsequently, the dissolution advantage was translated into the improved flux. Further, in vivo oral bioavailability was investigated for the dispersion prepared by quench cooling by using crystalline Dolutegravir as a control. The overall exposure of Dolutegravir was improved by 1.7 fold (AUC), while the maximum plasma concentration (Cmax) demonstrated 2 fold increase after comparing with crystalline Dolutegravir.

Supramolecular cyclodextrin complex: Diversity, safety, and applications in ocular therapeutics.

Approximately 30-70% of the existing and new chemical entities exhibit poor aqueous solubility. For topical ocular delivery, drug molecules need to possess both hydrophilic and lipophilic nature to enable absorption through the aqueous tear layer and permeation through the corneal lipophilic barrier. To overcome the aqueous solubility related issues, various techniques such as solid dispersion, particle size reduction, cyclodextrin complexation, co-solvency, prodrug, derivatization, and salt formation are being explored in the healthcare sector. Cyclodextrin inclusion complexation techniques have been established by several pharmaceutical industries for systemic administration allowing a transition from the lab to the clinics. Though cyclodextrins are exploited in ocular drug delivery, there are prevailing concerns regarding its absorption enhancing capacity and mechanism, retention at the ocular surfaces and, irritation and toxicity profiles. In the present review, the efforts taken by various research groups to address the concerns of using cyclodextrin and its derivatives in ocular therapeutics are summarized. Also, considerations and utility of cyclodextrin systems in fabricating newer formulations such as contact lens, inserts, and implants have been discussed in the review.