Contact lens as an emerging platform for ophthalmic drug delivery:A systematic review

The number of people with eye diseases has increased with the use of electronics.However,the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons.Although many drug delivery systems have been developed to overcome these problems,they have certain limitations.In recent years,the development of contact lenses that can deliver drugs for long periods with high bioavailability and without affecting vision has increased the interest in using contact lenses for drug delivery.Hence,a review of the current state of research on drug delivery contact lenses has become crucial.This article reviews the key physical and chemical properties of drug-laden contact lenses,development and classification of contact lenses,and features of the commonly used materials.A review of the methods commonly used in current research to create contact lenses has also been presented.An overview on how drug-laden contact lenses can overcome the problems of high burst and short release duration has been discussed.Overall,the review focuses on drug delivery methods using smart contact lenses,and predicts the future direction of research on contact lenses.

Prodrugs incorporated into nanotechnology-based drug delivery systems for possible improvement in bioavailability of ocular drugs delivery

Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.

Phytochemicals in ocular health: Therapeutic potential and delivery challenges

Diabetic retinopathy(DR) and age-related macular degeneration(AMD) are the leading causes of blindness in adults. The impact of these conditions on the quality of life is increasing in significance with a rise in life expectancy. The role of hyperglycemia, oxidative stress and inflammatory responses in the development and/or progression of DR and AMD, and several other sight threatening ocular diseases, is well established. In proliferative retinopathy, signals sent by the retina for nourishment, triggers the growth of fragile and abnormal blood vessels. Changes in ocular pressure may lead to rupture of these blood vessels causing severe vision problems. Recent in vitro and preclinical studies demonstrate that certain phytochemicals possessing potent antioxidant and anti-inflammatory activity and ocular blood flow enhancing properties may be very useful in the treatment of, or as a prophylactic measure for, DR and AMD. Apart from these properties they have also been investigated for their anti-bacterial, hormonal, enzyme stimulation, and anti-angiogenic activities. The attractive aspect of these potential therapeutic candidates is that they can act on multiplepathways identified in the etiology of DR, AMD, cataract and other ocular diseases. However, results from clinical trials have been somewhat ambiguous, raising questions about the concentrations of these bioflavonoids achieved in the neural retina following oral administration. Unfortunately, as of date, an efficient noninvasive means to deliver therapeutic agents/candidates to the back-of-the eye is still not available. This review examines some of these promising natural agents and discusses the challenges encountered in delivering them to the posterior segment ocular tissues through the oral route.

Narrative review-drug delivery in age-related macular degeneration

This narrative review highlights routes of ocular drug delivery for age-related macular degeneration(AMD).AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7%of blindness worldwide.Advanced AMD can be classified into two subtypes:late-stage dry AMD[known as geographic atrophy(GA)]and neovascular AMD(nAMD).GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium.Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium(RPE)or retina,a process known as choroidal neovascularization(CNV).Various targeted therapeutic options are currently available to reduce the progression rate and maintain vision in patients with nAMD.Intravitreal delivery of anti-VEGF protein treatments to halt CNV is currently the gold-standard of care for nAMD.Subretinal and suprachoroidal delivery approaches are also being explored for gene and molecular therapies.Advancements in nanotechnology and biomaterials have also led to the development of microscopic drug delivery systems,including hydrogels,microparticles,nanoparticles,implants,and liposomes.Gene therapy and stem cell therapy has recently emerged as a potential candidate treatment modality for AMD and other retinal degenerations.New drug targets and modalities have stimulated exciting developments in ocular drug delivery with the promise of greater efficacy and durability of AMD treatment.

iRGD decorated liposomes:A novel actively penetrating topical ocular drug delivery strategy

Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular drug administration,topical administration results in a drug bioavailability of less than 1%.iRGD modified drug delivery strategies have been developed for cancer therapy,however active targeting iRGD platforms for ocular drug delivery have yet to be explored.Herein,an iRGD modified liposomes was developed for ocular drug delivery via topical administration.The results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated manner.These findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.

Nanotechnology-based strategies for treatment of ocular disease

Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops,injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new,highly effective and important ocular nanomedicines.

Pediatric ocular nanomedicines：Challenges and opportunities

The eye is a highly complex,yet readily accessible organ within the human body.As such,the eye is an appealing candidate target for a vast array of drug therapies.Despite advances in ocular drug therapy research,the focus on pediatric ocular drug delivery continues to be highly underrepresented due to the limited number of degenerative ocular diseases with childhood onset.In this review,we explore more deeply the reasons underlying the disparity between ocular therapies available for children and for adults by highlighting diseases that most commonly afflict children（with focus on the anterior eye） and existing prognoses,recent developments in ocular drug delivery systems and nanomedicines for children,and barriers to use for pediatric patients