Ocular Delivery System Research Articles

Overview of Emulgel as Emergent Topical Delivery: Recent Applications and Advancement

Emulgel is an emerging delivery system with added advantages over other topical delivery systems which is proven to be boon for cosmetics and dermatology. Emulgels are emulsion which is converted to Gel, which will make it a non greasy and enhances patient compliance. The amalgamation of the two systems would be advantages in term of high drug loading capacity and low skin irritation, site specific targeting avoiding first-pass metabolism and increase in bioavailability. Work carried out by researchers proved that, Emulgel/ Nanoemulgel loaded with drugs has been found effective in many topical disorders and it is emerging as potential drug delivery system in area of dermatology. In the present review current research works that carried out on Emulgel and nano emulgels are discussed and also highlighted the recent applications of Emulgel in transdermal as well as dental, ocular, vaginal, and other delivery system.

In-Situ Ocular Gel Pharmaceutical Delivery System: A Recent Review

Ocular Drug Delivery has been a key challenge and attractive field for the pharmaceutical scientist due to peerless anatomy and physiology of eye. Glaucoma, dry eye syndrome, keratitis, endophthalmitis, trachoma, and conjunctivitis are just a few of the conditions that can affect the eye. In order to accomplish efficient ocular treatment within the eye, At the point of action, an appropriate supply of active substances must be given and sustained. Due to fast precorneal medication loss, traditional treatment has a low bioavailability. The bioavailability of a medicine is also influenced by static and dynamic barriers. To address the limitations of traditional treatment, significant efforts are being made to develop innovative medication systems for ocular delivery. When a drop is injected into the eye, it goes through a sol-gel transition and forms a cul-de-sac. The in-situ gel system, which comprises thermally triggered, pH triggered, and ion cross linking systems, is the subject of this review. It includes a step-by-step procedure for preparing the pH-triggered system as well as assessment parameters.
 Keywords: Conventional dosage form, Anatomy and physiology in eye, In-situ gel.

Preparation and functional evaluation of electrospun polymeric nanofibers as a new system for sustained topical ocular delivery of itraconazole

Due to the rapid clearance of external agents from the surface of the cornea, conventional ocular formulations usually require frequent and long duration of administration to achieve a therapeutic level of the drug on the cornea which can be conquered using prolonged-release nanofibrous inserts. In the present study, for the first time, polymeric nanofibers of itraconazole (ITZ), a potent triazole antifungal agent, were prepared as ocular inserts to enhance the topical ocular delivery of the drug. Three different nanofibers were prepared by electrospinning using polyvinyl alcohol-cellulose acetate and polycaprolactone-polyethylene glycol 12 000 polymeric blends. Nanofibers indicated uniform structures with the mean diameter ranging between 137 and 180 nm. Differential scanning calorimetry and Fourier-transform infrared spectroscopy confirmed the amorphous state of the drug in the formulations and the no drug-polymer interaction. Appropriate stability, suitable flexibility, and 2.2–3.9 MPa tensile strength were observed. Formulations indicated antifungal efficacy against Candida albicans and Aspergillus fumigatus and cell viability >70% at different concentrations. Results of bioassay against Candida albicans exhibited prolonged in vitro release of 50–70% of ITZ for almost 55 days. The results suggested that the nanofibers could be considered suitable for prolonged delivery of the ITZ as an antifungal requiring frequent and long duration of administration.

Development and evaluation of Panax notoginseng saponins contained in an in situ pH-triggered gelling system for sustained ocular posterior segment drug delivery

Abstract Objective: This study aimed to lay the foundation for the research on Panax notoginseng saponins (PNS) in pH-sensitive in situ gel and the development and improvement of related preparations. Methods: We used Carbopol®940, a commonly used pH-sensitive polymer, and the thickener hydroxypropyl methylcellulose (HPMC E4M) as an ophthalmic gel matrix to prepare an ophthalmic in situ gel of PNS. In addition, formula optimization was performed by assessing gelling capability with the results of in vitro release studies. In vitro (corneal permeation, rheological, and stability) and in vivo (ocular irritation and preliminary pharmacokinetics in the vitreous) studies were also performed. Results: The results demonstrated that the in situ gelling systems containing PNS showed a sustained release of the drug, making it an ideal ocular delivery system for improving posterior ocular bioavailability. Conclusions: This study lays the foundation for the research of PNS contained in an in situ pH-triggered gel as well as the development and improvement of related preparations. It concurrently traditional Chinese medicine with a contemporary in situ gelling approach to provide new directions for the treatment of posterior ocular diseases such as diabetic retinopathy.

DISPOSABLE CONTACT LENS-BASED OCULAR DELIVERY OF MOXIFLOXACIN : A NOVEL APPROACH

Objective: In the present research, the main objective was to investigate the possibility of designing, fabricating, and optimizing a disposable ocular film-based drug delivery system. Methods: Moxifloxacin hydrochloride was loaded onto the prepared disposable ocular films by the soaking method. Results: The drug loading conditions were studied, and it was found that the maximum drug loading was achieved in 3 hours at pH 6.5 of the drug solution. It was also observed that the drug loading efficacy and in vitro drug release profile can be monitored by varying the ocular film composition. The ocular films were then characterized for thickness uniformity, size uniformity, weight uniformity, swelling index, surface pH, breaking on elongation, folding endurance, bio-adhesive strength, transparency, drug loading efficiency, moisture content, morphological characteristics, and in vitro drug release profiles. Conclusion: Based on the results, it was concluded that the developed disposable ocular films demonstrate a significant prolonged drug release within the therapeutic range of up to 12 h, which is promising as a novel disposable contact lens-based ocular drug delivery system.

DISCOSOMES: A FUTURISTIC UPHEAVAL IN VESICULAR DRUG DELIVERY

The formulation system employed to convey pharmaceutical drugs compound in the body to attain the desired therapeutic effect at a predetermined rate depending on pharmacological aspects, drug profile, and physiological conditions can be referred to as a novel drug delivery system (NDDS). Due to the intricately sensitive anatomy and physiology of the eye pharmacologist find the ocular delivery system to be more involuted than other routes. Pre-corneal, static and dynamic is the 3 types of ophthalmic barriers, which along with the inflow and outflow of lacrimal fluids, nasolacrimal drainage, are some of the germane factors that affect bioavailability. Unlike conventional dosage forms, where the distribution of drugs in non-targeted body fluids and tissues transcends the quantity of required drug in targeted tissues and causes repercussions, these modified drug delivery systems surpass the ocular barriers and adverse reactions, emphasizing on less invasive, prolonged action. It also promotes sustained release formulation that subjugates the drug loss or degradation to treat many ocular diseases effectively. The current review recapitulates the fundamentals of discosomes, a type of vesicular drug delivery system that acts as a vehicle for the drug delivery of both hydrophilic and lipophilic drugs. Discosomes are giant, disc-shaped structures modified from niosomes by arresting the vesicles at the discosome phase. Due to their idiosyncratic size, it provides all due benefits compared to other ocular drug delivery systems. From the review, it can be culminated that discosomes are a potential subject of opposition and opportunities in the arena of safe and effective ocular drug delivery.

Stable Atropine Loaded Film As a Potential Ocular Delivery System For Treatment Of Myopia.

The objective of the present study was to prepare stable and high bioavailability ocular atropine loaded films (ATR-films) as potential ocular drug delivery systems for the treatment of myopia. ATR-films were prepared by the solvent casting method and the physical properties of films were evaluated including thickness, water content, light transparency, disintegration time, and mechanical properties. FT-IR, DSC, XRD, TGA, AFM, and Raman spectroscopy were performed to characterize the film. The stability test was conducted under different conditions, such as high humidity, high temperature, and strong light. The pharmacokinetic study and irritation assessment were conducted in rabbits. The efficacy of ATR-films was evaluated by refraction and ocular biometry in myopia guinea pigs. After optimizing the formulation, the resulting ATR-film was flexible and transparent with lower water content (8.43% ± 1.25). As expected, the ATR-film was stable and hydrolysate was not detected, while the content of hydrolysate in ATR eye drops can reach up to 8.1867% (limit: < 0.2%) in the stability study. The safety assessment both in vitro and in vivo confirmed that the ATR-film was biocompatible. Moreover, the bioavailability (conjunctiva 3.21-fold, cornea 2.87-fold, retina 1.35-fold, sclera 2.05-fold) was greatly improved compared with the ATR eye drops in vivo pharmacokinetic study. The pharmacodynamic study results showed that the ATR-film can slow the progress of form-deprivation myopia (~ 100 ± 0.81D), indicating that it has a certain therapeutic effect on form-deprivation myopia. The ATR-film with good stability and high bioavailability will have great potential for the treatment of myopia.

Formulation and Pathohistological Study of Mizolastine-Solid Lipid Nanoparticles-Loaded Ocular Hydrogels.

BackgroundMizolastine (MZL) is a dual-action nonsedating topical antihistamine anti-inflammatory agent that is used to relieve allergic conditions, such as rhinitis and conjunctivitis. Solid lipid nanoparticles (SLNs) are advanced delivery system in ophthalmology, with the merits of increasing the corneal drug absorption and hence improved bioavailability with the objective of ocular drug targeting.MethodsFirst, MZL was formulated as MZL-SLNs by hot homogenization/ultrasonication adopting a 32 full factorial design. Solid-state characterization, in vitro release, and stability studies have been performed. Then, the optimized MZL-SLNs formula has been incorporated into ocular hydrogels using 1.5% w/v Na alginate and 5% w/v polyvinylpyrrolidone K90. The gels were evaluated via in vitro release as well as in vivo studies by applying allergic conjunctivitis congestion in a rabbit-eye model.ResultsThe optimized formula (F4) was characterized by the highest entrapment efficiency (86.5±1.47%), the smallest mean particle size (202.3±13.59 nm), and reasonable zeta potential (−22.03±3.65 mV). Solid-state characterization of the encapsulation of MZL in SLNs was undertaken. In vitro results showed a sustained release profile from MZL-SLNs up to 30 hours with a non-Fickian Higuchi kinetic model. Stability studies confirmed immutability of freeze-dried MZL-SLNs (F4) upon storage for 6 months. Finally, hydrogel formulations containing MZL-SLNs, proved ocular congestion disappearance with completely repaired conjunctiva after 24 hours. Moreover, pretreatment with MZL-SLNs–loaded hydrogel imparted markedly decreased TNF-α and VEGF-expression levels in rabbits conjunctivae compared with post-treatment with the same formula.ConclusionMZL-SLNs could be considered a promising stable sustained-release nanoparticulate system for preparing ocular hydrogel as effective antiallergy ocular delivery systems.

Vesicular phospholipid gels as topical ocular delivery system for treatment of anterior uveitis

In this paper, we developed a vesicular phospholipid gels (VPGs) for topical ocular delivery of flurbiprofen (FLB) to treat anterior uveitis. FLB loaded VPGs (FLB VPGs), composed of FLB and egg yolk lecithin, were prepared by high-pressure homogenization technique. The effects of egg yolk lecithin content and homogenization pressure on properties of FLB VPGs, including size, encapsulation efficiency, yield and in vitro release profile were investigated. The resultant FLB VPGs were characterized by the transmission electron microscopy, differential scanning calorimetry, X-ray diffraction, fourier transform infrared spectroscopy, rheological behavior, and storage stability. Corneal permeation experiments revealed that VPGs could improve the transcorneal delivery of FLB under ex vivo conditions. VPGs were nonirritant toward to the rabbit eye, as indicated by slit lamp observation and histological observation. The results of tear pharmacokinetics and in vivo fluorescence imaging showed that VPGs could significantly prolong the precorneal retention time. In vivo biodistribution study indicated that VPGs could significantly improve drug bioavailability in ocular tissues. Moreover, FLB VPGs exhibited excellent anti-inflammatory effect in endotoxin induced uveitis in rabbits. Overall, VPGs are a promising ophthalmic drug delivery system for the treatment of anterior uveitis.

A composite System Combining Self-Targeted Carbon Dots and Thermosensitive Hydrogels for Challenging Ocular Drug Delivery

We developed a composite system combining self-targeted carbon dots and thermosensitive in situ hydrogels for ocular drug delivery of diclofenac sodium (DS). DS-CDC-HP nanoparticles were prepared by loading DS on the surface of CDC-HP via electrostatic interactions. An orthogonal experimental design was selected to screen the optimal thermosensitive hydrogel matrices and then DS-CDC-HP nanoparticles were embedded to form the composite system. The physicochemical properties and release behavior of this system were characterized, and in vivo fluorescence imaging was carried out. Corneal penetrability and in vitro cellular studies (cytotoxicity, cell imaging and cell uptake) were performed to test the feasibility and potential of this ocular delivery system. Finally, the optimal gel matrix consisting of Poloxamer 407: Poloxamer 188: HPMC E50 was 21:1:1 (w/v %), and the gelation temperature before adding artificial tear fluid was 26.67°C and 34.29°C, respectively. This system has the characteristics of biphasic drug release. In addition, the corneal penetrability and in vivo fluorescence study indicated that corneal transmittance was enhanced and drug retention time was extended. Cellular studies revealed that the DS-CDC-HP-Gel has good cytocompatibility and CD44 targeting. In summary, this composite system combines carbon dots with hydrogels, offering new potential for ocular drug delivery.

A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization, Ex-Vivo Imaging, and In Vivo Evaluation.

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.

Development of lipid-based microsuspensions for improved ophthalmic delivery of gentamicin sulphate.

Aim: Anterior eye segment disorders are treated with eye drops and ointments, which have low ocular bioavailability necessitating the need for improved alternatives. Lipid microsuspension of gentamicin sulphate was developed for the treatment of susceptible eye diseases. Materials & methods: Lipid microsuspensions encapsulating gentamicin sulphate were produced by hot homogenization and evaluated. Ex vivo permeation and ocular irritancy tests were also conducted. Results & conclusion: Stable microsuspensions with high entrapment efficiency and satisfactory osmolarities were obtained. Release studies achieved 49-88% in vitro release at 12h with sustained permeability of gentamicin compared with conventional gentamicin eye drop (Evril®). No irritation was observed following Draize's test. The microsuspensions have great potential as ocular delivery system of gentamicin sulphate.

Effectiveness of an ocular adhesive polyhedral oligomeric silsesquioxane hybrid thermo-responsive FK506 hydrogel in a murine model of dry eye

Dry eye is a common ocular disease that results in discomfort and impaired vision, impacting an individual's quality of life. A great number of drugs administered in eye drops to treat dry eye are poorly soluble in water and are rapidly eliminated from the ocular surface, which limits their therapeutic effects. Therefore, it is imperative to design a novel drug delivery system that not only improves the water solubility of the drug but also prolongs its retention time on the ocular surface. Herein, we develop a copolymer from mono-functional POSS, PEG, and PPG (MPOSS-PEG-PPG, MPEP) that exhibits temperature-sensitive sol-gel transition behavior. This thermo-responsive hydrogel improves the water solubility of FK506 and simultaneously provides a mucoadhesive, long-acting ocular delivery system. In addition, the FK506-loaded POSS hydrogel possesses good biocompatibility and significantly improves adhesion to the ocular surface. In comparison with other FK506 formulations and the PEG-PPG-FK506 (F127-FK506) hydrogel, this novel MPOSS-PEG-PPG-FK506 (MPEP-FK506) hydrogel is a more effective treatment of dry eye in the murine dry eye model. Therefore, delivery of FK506 in this POSS hydrogel has the potential to prolong drug retention time on the ocular surface, which will improve its therapeutic efficacy in the management of dry eye.

Advantages and Disadvantages of Using Magnetic Nanoparticles for the Treatment of Complicated Ocular Disorders.

Nanomaterials provide enormous opportunities to overcome the limitations of conventional ocular delivery systems, such as low therapeutic efficacy, side effects due to the systemic exposure, or invasive surgery. Apart from the more common ocular disorders, there are some genetic diseases, such as cystic fibrosis, that develop ocular disorders as secondary effects as long as the disease progresses. These patients are more difficult to be pharmacologically treated using conventional drug routes (topically, systemic), since specific pharmacological formulations can be incompatible, display increased toxicity, or their therapeutic efficacy decreases with the administration of different kind of chemical molecules. Magnetic nanoparticles can be used as potent drug carriers and magnetic hyperthermia agents due to their response to an external magnetic field. Drugs can be concentrated in the target point, limiting the damage to other tissues. The other advantage of these magnetic nanoparticles is that they can act as magnetic resonance imaging agents, allowing the detection of the exact location of the disease. However, there are some drawbacks related to their use in drug delivery, such as the limitation to maintain efficacy in the target organ once the magnetic field is removed from outside. Another disadvantage is the difficulty in maintaining the therapeutic action in three dimensions inside the human body. This review summarizes all the application possibilities related to magnetic nanoparticles in ocular diseases.

In-Situ Forming Polymeric Drug Delivery Systems for Ophthalmic Use: An Overview

Delivery of drug into the ocular region is hindered by the protective layers that encapsulate the eyes, it has always been a major problem to get an effective bioavailability of the active drug in the ocular region due to the low precorneal resident time of most of the ocular delivery systems specifically convention once such as ointment, solution and suspension, as a result, most of the delivery systems are not capable of effectively treating ocular diseases. Several works have and are being carried out to overcome this problem one of which is using in-situ forming polymeric systems. Ocular In-situ gelling systems are a novel class of ocular drug delivery systems that are initially in a solution form but instantaneously gets converted into a viscous gel upon introduction or installation in the ocular cavity from which the active drugs get released in a sustained manner. This sol-to-gel phase transition depends upon various factors like change in pH, ion presence and change in temperature. Gel formed after the transformation has preferred viscosity along with bio-adhesive property, which increases the gel’s resident time in the ocular area and also releases the drug in a prolonged and sustained manner unlike conventional eye drops and ointments. This review emphasizes various ocular in-situ systems namely, pH triggered, Ion activated, and Temperature triggered systems which have prolonged residence time in the cul-de-sac area of the eye, hence increasing the ocular bioavailability.&#x0D; Keywords: In-situ gel, Ocular Drug delivery, Ocular Bioavailability, Polymer

Gamma sterilization and in vivo evaluation of cationic nanostructured lipid carriers as potential ocular delivery systems for antiglaucoma drugs

Solid lipid nanoparticles and nanostructured lipid carriers showed promising results for enhancement of ocular bioavailability of drugs with poor corneal permeability. One of these drugs is methazolamide, which is an orally administered carbonic anhydrase inhibitor for glaucoma treatment. However, sterilization by autoclaving may result in loss of the physical properties of lipid nanoparticles such as particle size and surface charge. Here, we evaluated gamma radiation as an alternative sterilization method. Methazolamide loaded nanostructured lipid carriers were optimized using 23 factorial design. Optimized formulations contained 6% lipid (85% solid lipid (Cetostearyl alcohol and glyceryl behenate) and 15% oil either medium chain triglycerides or isopropyl myristate) stabilized by 2% polysorbate 80 and 0.15% stearylamine. Nanoparticles were cationic, smaller than 500 nm, and had an entrapment efficiency of about 30%. They released methazolamide within 8 hours and showed a 5-fold enhanced reduction in intraocular pressure compared to methazolamide solution. Gamma sterilization was superior to autoclaving in preserving entrapped methazolamide, size, and surface charge of lipid nanoparticles. These findings demonstrate that gamma radiation is a viable alternative to autoclaving for sterilizing lipid nanoparticles. Moreover, this proves that nanostructured lipid carriers enhance pharmacological response of topically administered methazolamide for treating glaucoma.

Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye.

Eye drop formulations allowing topical treatment of retinal pathologies have long been sought as alternatives to intravitreal administration. This study aimed to assess whether a novel nanostructured microemulsions system (NaMESys) could be usefully employed to deliver sorafenib to the retina following topical instillation. NaMESys carrying 0.3% sorafenib (NaMESys-SOR) proved to be cytocompatible in vitro on rabbit corneal cells, and well-tolerated following b.i.d. ocular administration to rabbits during a 3-month study. In rats subject to retinal ischemia-reperfusion, NaMESys-SOR significantly inhibited retinal expression of tumor necrosis factor-alpha (TNFα, 20.7%) and inducible nitric oxide synthase (iNos, 87.3%) mRNAs in comparison to controls. Similarly, in streptozotocin-induced diabetic rats, NaMESys-SOR inhibited retinal expression of nuclear factor kappa B (NFκB), TNFα, insulin like growth factor 1 (IGF1), IGF1 receptor (IGF1R), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2) mRNAs by three-fold on average compared to controls. Furthermore, a reduction in TNFα, VEGFR1 and VEGFR2 protein expression was observed by western blot. Moreover, in mice subject to laser-induced choroidal neovascularization, NaMESys-SOR significantly inhibited neovascular lesions by 54%. In conclusion, NaMESys-SOR was shown to be a well-tolerated ophthalmic formulation able to deliver effective amounts of sorafenib to the retina, reducing proinflammatory and pro-angiogenic mediators in reliable models of proliferative retinopathies. These findings warrant further investigations on the full therapeutic potential of NaMESys-SOR eye drops, aiming to address unmet needs in the pharmacotherapy of retinal neovascular diseases.

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research.

Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution–gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.

Development and Evaluation of Acyclovir Loaded Poly Lactic-Co-Glycolic Acid Nanoparticles for Ocular Drug Delivery

Objectives: The objective of present study aim towards promising potential of acyclovir containing Poly Lactic-Co-Glycolic Acid based nanoparticles for delivering drug to ocular cavity and could be view as alternative to conventional dosage form. Methods: The acyclovir containing Poly Lactic- Co-Glycolic Acid based polymeric nanoparticles were prepared by using nanoprecipitation technique and the optimized formulation was evaluated for particle size, encapsulation efficiency, in vitro release study, Differential Scanning Calorimetry, X-Ray Diffraction, Scanning Electron Microscopy, redispersibility, swelling index, ex vivo study and stability studies. Results: Among all the developed polymeric Nanoparticle formulations, optimized formulation (F1) showed Zeta Particle size 269 nm, Encapsulation Efficiency 90.1%. In vitro release studies exhibited 98.78% of drug release within 3 hr and ex-vivo studies indicate optimize formulation is nonirritant. Differential Scanning Calorimetry and X-Ray Diffraction indicate the optimized formulation show amorphous form. Scanning Electron Microscopy of optimized formulation show cylindrical in shape and their size was in the nanometer range. In terms of particle size, drug loading performance, redispersibility, in vitro release characteristics, sterility and better ocular tolerability, the formulated acyclovir nanoparticles were found to be a suitable and potential natural carrier. Suitable results have been shown in the stability study of acyclovir from nanoparticles. Conclusion: Therefore, the results concluded that Polymeric Nanoparticle could be considered as ocular delivery system for the prolong residence time of precorneal drug and increase penetration of corneal drug.

Biological drug therapy for ocular angiogenesis: Anti-VEGF agents and novel strategies based on nanotechnology.

Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti‐VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off‐label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti‐VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti‐VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti‐VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer‐reviewed published papers relevant to anti‐VEGF treatments and nanoparticles developed as ocular anti‐VEGF delivery system.