Ocular Drug Delivery Systems Research Articles

Chitosan-Coated PLGA Nanoparticles for Enhanced Ocular Anti-Inflammatory Efficacy of Atorvastatin Calcium.

BackgroundAtorvastatin calcium (AT) is an ocular anti-inflammatory with limited bioavailability when taken orally due to its low solubility in low pH and extensive first-pass effect. To overcome these problems, AT was entrapped in polymeric nanoparticles (NPs) to improve surface properties and sustained release, in addition to achieving site-specific action.MethodsAT was entrapped in chitosan (CS)-coated polylactic-co-glycolic acid (PLGA) NPs to form AT-PLGA-CS-NPs (F1). F1 and free AT were embedded in thermosensitive Pluronic®127-hydroxypropyl methylcellulose (HPMC) to form thermosensitive gels (F2) and (F3) while F4 is AT suspension in water. F1 was assessed for size, surface charge, polydispersity index (PDI), and morphology. F2 and F3 were examined for gelation temperature, gel strength, pH, and viscosity. In vitro release of the four formulations was also investigated. The ocular irritancy and anti-inflammatory efficacy of formulations against prostaglandin E1-(PGE1) induced ocular inflammation in rabbits were investigated by counting the polymorphonuclear leukocytes (PMNs) and protein migrated in tears.ResultsOval F1 of 80.0–190.0±21.6 nm exhibited a PDI of 0.331 and zeta potential of ‏17.4±5.62 mV with a positive surface charge. F2 and F3 gelation temperatures were 35.17±0.22°C and 36.93±0.31°C, viscosity 12,243±0.64 and 9759±0.22 cP, gel strength 15.56±0.6 and 12.45±0.1 s, and pHs of 7.4±0.02 and 7.4±0.1, respectively. In vitro release of F1, F2, F3, and F4 were 48.21±0.31, 26.48±0.5, 84.76±0.11, and 100% after 24 hrs, respectively. All formulations were non-irritant. F2 significantly inhibited lid closure up to 3 h, PMN counts and proteins in tear fluids up to 5 h compared to other formulations.ConclusionAT-PLGA-CS-NP thermosensitive gels proved to be successful ocular anti-inflammatory drug delivery systems.

The Study of Stability and Location of Chloramphenicol in Newly Formed Microemulsion Based Ocular Drug Delivery System

Microemulsions (MEs) are homogeneous, optically clear and thermodynamically stable systems intended to increase the bioavailbility, solubility, and entrapment of drugs. Anew system of oil-in-water MEs was formulated for the entrapment of chloramphenicol, consisting of isopropyl myristate/Tween 60/80 with short-chain alcohol and phosphate buffer (pH 7). The 1H NMR spectroscopy was used for investigation of the drug location in formulation. The drug is entrapped in a hydrophilic shell of ME, which consists of oxyethylene groups. It was revealed by 1H NMR study that the drug stability increases due to its screening from bulk water. The formulated MEs were evaluated for the phase composition, pH, refractive index, conductivity, surface tension, partition coefficient, and viscosity. These characteristics suggested that the optimized MEs were stable and optically clear and could be used as an efficient ocular drug carrier.

Integrated nanovesicular/self-nanoemulsifying system (INV/SNES) for enhanced dual ocular drug delivery: statistical optimization, in vitro and in vivo evaluation.

Ocular drug administration is usually problematic and suffers low bioavailability due to several physiological and biological factors that hinder their effective treatment. Terconazole (TZ) is considered as one of the effective ocular antifungal agents that is usually administrated intravitreally for higher efficacy. The aim of the work in this study is to formulate a TZ-loaded ocular drug delivery system with high efficiency and good tolerability. First, TZ-loaded bile-based nanovesicles (BBNV) were prepared and the formulation variables (namely, Span 60, cholesterol, and sodium deoxycholate levels) were optimized based on the results of the entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP) using Box-Behnken statistical design. The optimized system was formulated using 73.59mg Span 60, 1.28mg cholesterol, and 3.11mg sodium deoxycholate. The formulated system showed vesicles with PS of 526nm, - 42.2mV ZP, and 93.86% EE%. TZ release, cellular uptake, and cytotoxicity of the optimized system were evaluated in vitro. In addition, in vivo assessment of its safety was conducted histopathologically and via ocular irritation test to ensure the ocular tolerance of the system. Afterwards, the optimized TZ-loaded BBNV was integrated into a self-nanoemulsifying system (SNES) to allow faster TZ release for immediate antifungal effect, enhanced ocular residence, and improved ocular permeation. TZ release study revealed more than 2 folds increment in drug release rate from the integrated system compared to BBNV alone. Finally, this integrated system was assessed for its antifungal activity in vivo where it demonstrated higher antifungal activity against induced Candida albicans infection. Graphical abstract.

Use of chitosan as pharmaceutical excipient in ocular drug delivery systems: Sterilization and pharmacokinetics.

The use of chitosan as a pharmaceutical excipient in the ocular field is already established. Nevertheless, some aspects related to its ocular administration, such as sterilization and excipient's pharmacokinetics, remain unclear. So, in this study, we evaluated those two relevant aspects, related to chitosan administration in eye. We used chitosan-based ocular inserts (CI) as formulation model. CI were produced by solvent/casting method and sterilized by saturated steam. Sterilization was confirmed by direct inoculation of inserts in suitable microbiological growth media. Physicochemical characterization of inserts before and after sterilization was performed. Results suggested that, although steam sterilization changed the arrangement of the matrix, the heat and the humidity did not modify the structure of the main polymeric chain. Pharmacokinetics of CI radiolabeled with technetium-99m (99m Tc) was assessed by scintigraphic images and ex vivo biodistribution study, after ocular administration in male Wistar rats. Scintigraphic and images analysis and ex vivo biodistribution study showed that the insert remained mainly in the eye until 6 hr after administration and its degradation products began to migrate to the abdominal cavity after 18 hr. Together, these data represent an important step forward the manufacturing and the clinical application of CI in the ophthalmic field.

Novel ultrasmall nanomicelles based on rebaudioside A: A potential nanoplatform for the ocular delivery of pterostilbene.

Rebaudioside A (RA) self-assembled into ultrasmall nanomicelles can be utilized as ocular drug delivery system; nevertheless, the therapeutic efficacy of RA micelles has not evaluated thus far. In this manuscript, the RA micelles are thought to strengthen the therapeutic effects of pterostilbene (Pt). Results showed that Pt can be highly encapsulated into RA micelles with ultrasmall particle sizes (3.99±0.03nm) with a uniform distribution (polydispersity index, PDI=0.184±0.008). RA-Pt exhibited pronounced improvement for the in vitro antioxidant activity and the in vitro membrane permeation of Pt. RA-Pt exhibited good ocular tolerance. The use of RA-Pt led to the significant improvement in the in vivo intraocular permeation of Pt as well as the improvement in the in vivo anti-inflammatory efficacy. The in vivo evaluation of antioxidant effects revealed that RA-Pt exhibits improvement in suppressing the generation of oxidative stress and inducing the enzymes of reactive oxygen species (ROS) degradation. Furthermore, RA-Pt was confirmed to exhibit a strong treatment efficiency for corneal alkali burns. These findings indicate that RA-based self-assembled ultrasmall nanomicelles demonstrate tremendous potential toward the improvement in the ocular bioavailability as well as a therapeutic effect of poor aqueous soluble drugs such as Pt.

Preparation and in vitro characterization of monoclonal antibody ranibizumab conjugated magnetic nanoparticles for ocular drug delivery

Gold coated magnetite nanoparticles were prepared and coated with ranibizumab as an ocular drug delivery system. The surface morphologies of the nanoparticles were determined by Scanning Electron Microscopy (SEM). The size and surface charge were determined by using the dynamic light scattering (DLS) technique. Crystallographic properties of the gold coated Fe3O4 nanoparticles were recorded on X-ray diffractometer (XRD) the XRD pattern of nanoparticlees were shown to have uniqe Fe3O4 and gold peaks. Conjugation of ranibizumab onto nanoparticles was achieved using the physical adsorption method. The amount of ranibizumab on the surface of the nanoparticles was determined by thermogravimetric analysis (TGA). In the in vitro release studies performed using UV spectroscopy; it was found that almost 60% of antibodies were released within the first 30 minutes. Antibody activity after release studies was also proved with ELISA. Non-toxicity of gold coated Fe3O4 particles were proved with MTT. Results of the studies, showed that the antibody conjugated magnetic nanoparticle system could be a potential treatment system for ocular diseases.

Clinical Evaluation of a Novel Electromechanical Topical Ocular Drug Delivery System: Two Phase 1 Proof of Concept Studies.

PurposeSelf-administration of topical ophthalmic therapies remains challenging for many patients as errors due to improper technique are common. The aim of the current studies was to evaluate a novel electromechanical topical ocular drug delivery device designed to facilitate precise dosing and accurate delivery with substantially lower drug exposure than conventional eye drops.Patients and MethodsTwo randomized Phase 1 studies were performed to evaluate the efficacy and safety of a single dose of a topical ophthalmic solution administered as a ~9 μL microfluid stream via the test device compared with a ~30–40 μL drop delivered via conventional dropper in healthy subjects (Trial 1) and glaucoma patients (Trial 2). In Trial 1, a 1% tropicamide/2.5% phenylephrine solution was administered via the test device in one eye and by conventional dropper in the contralateral eye. Pupil dilation was measured at 30 min intervals post-instillation and subject comfort was assessed using a visual analogue scale (range, 0–100). In Trial 2, patients were randomized to receive latanoprost 0.005% via the test device or conventional dropper. Intraocular pressure was measured at baseline and 4–8 hrs post-instillation.ResultsIn Trial 1 (N=20), mean (SD) pupil diameter 30 mins post-instillation increased by 3.4 (0.9) and 3.5 (1.0) mm in the test and control eyes, respectively. The mean comfort score was 81.7 for the test device versus 57.3 for conventional dropper delivery. In Trial 2 (N=18), the mean change in intraocular pressure following administration of latanoprost was –5.0 (1.8) and –4.3 (3.3) mm Hg in the test and control groups, respectively. No serious adverse events were observed in either study.ConclusionAdministration of a single dose of topical ophthalmic therapy via an electromechanical drug delivery device resulted in comparable effects on pupil dilation and intraocular pressure with lower drug exposure and increased patient comfort compared with conventional dropper delivery.

Electrospun nanofibers – A promising solid in-situ gelling alternative for ocular drug delivery

A serious problem of the treatment of eye diseases is the very short residence time of the drug. The majority of the drug is cleared within few seconds due to the poor capability of the eye to accommodate additional liquids. We developed a new ocular drug delivery system, which is applied in dry form and forms immediately a gel after administration. The system is based on gellan gum/pullulan electrospun nanofibers. The rheological behavior of the spinning solution was investigated followed by further characterization of the in situ formed gel. Three-dimensional X-ray imaging with nanometric resolution (nano-CT) and electron scanning microscopy were used for a detailed characterization of the diameter and alignment of the fibers. A high porosity (87.5 ± 0.5%) and pore interconnectivity (99%) was found. To ensure a good fit to the eye anatomy, the prepared fibers were shaped into curved geometries. Additionally, a new innovative moistening chamber for the in vitro determination of the ocular residence time in porcine eyes was developed which mimics the tear turnover. A clear prolongation of the fluorescein residence time compared to conventional eye drops was achieved with the application of the curved nanofiber in situ gelling mat. In summary, the developed in situ gelling system with adapted geometry is a promising alternative system for ocular drug delivery.

Chitosan-N-acetylcysteine modified HP-β-CD inclusion complex as a potential ocular delivery system for anti-cataract drug: Quercetin

The aim of this study was to develop a novel ocular drug delivery system based on the hydroxypropyl beta cyclodextrin (HP-β-CD) inclusion complex coated with the synthesized chitosan-N-acetyl-l-cysteine conjugate (CS-NAC) for the hydrophobic drug quercetin. The inclusion complex was prepared by the solvent evaporation method, and the concentration of HP-β-CD and CS-NAC was optimized by isolated corneal penetration test. The optimized concentration of HP-β-CD and CS-NAC was 20% (w/v) and 0.1% (w/v), respectively. The CS-NAC/quercetin-HP-β-CD had the effect on improving the ocular penetration with little ocular irritation and could increase the ocular distribution significantly. Meanwhile, Coumarin-6 (C6) labelled CS-NAC/C6-HP-β-CD possessed enhanced fluorescence and located deeper into the epithelium of cornea at the same time point compared with the uncoated one. It could also transport drug through the corneal epithelium by intracellular routes except for intercellular routes. Furthermore, it could delay the occurrence of cataract about 1 d when administrated with full-dosage quercetin. The HP-β-CD inclusion complex coated with CS-NAC is a safe and promising ocular drug delivery system for improving the bioavailability and corneal penetration of hydrophobic drug like quercetin.

Application of nanoparticles in ocular drug delivery systems

Application of a drug in the form of eye drops represents easiest, safest and, at the moment, the most common non-invasive method of ocular drug application. Other conventional ophthalmic formulations in the form of aqueous and oily solutions, ointments, suspensions and emulsions were established to increase bioavailability, solubility and pericorneal retention time of a drug, compared to eye drops. But in the last few decades, nanotechnology-based ophthalmic formulations have been intensively analysed in the area of drug delivery to anterior and posterior parts of the eye. Systems based on nanotechnology with adequate nanoparticle size can be formed to achieve lower irritation and inflammation and better bioavailability and interaction of a drug with ocular tissue. The nanocarrier-based approach led to the development of nanoparticles, nanosuspensions, nanoemulsions, liposomes, nanomicelles, niosomes, nanocrystals and dendrimers for ocular drug delivery. These systems have significant advancements compared to conventional systems, particularly if they are observed as systems for drug delivery to the posterior eye part. Besides advantages, the nanoparticle use in these circumstances could be a reason for concern, because of certain toxic effects noticed in some studies. In this article, we aim to provide an overview of the potential of incorporating an active pharmaceutical ingredient into nanoparticles investigated in the therapy of anterior and posterior eye segment conditions. We will discuss the most important improvements that have been accomplished in the development of nanoparticle-based formulations for the treatment of glaucoma, autoimmune uveitis, age-associated macular degeneration and corneal and choroidal neovascularization.

Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime.

Endophthalmitis is a rare, but serious, intravitreal inflammatory disorder that can arise after cataract surgery. The intracameral injection of 1 mg cefuroxime (CEF) followed by three-times daily antibiotic topical administration for a week is generally recognized as the routine method of prophylaxis after cataract surgery. This procedure is controversial because of both the low efficacy and the low adherence to therapy by elderly patients. A unique slow release antibiotic intravitreal injection could solve these problems. The objective of the present study was to design ophthalmic nanocomposite delivery systems based on in situ gelling formulations that undergo sol-to-gel transition upon change in temperature to prolong the effect of CEF. Oil in water (O/W) microemulsion (µE) and solid lipid nanoparticles (SLN), obtained with an innovative formulation technology called cold microemulsion dilution, were evaluated as ocular drug delivery systems for CEF. Drug entrapment efficiency up to 80% was possible by esterifying CEF with 1-dodecanol to obtain dodecyl-CEF (dCEF). Both dCEF-loaded SLN and µE were then added with Pluronic®F127 (20% w/v) to obtain a nanocomposite hydrogel-based long acting system. The prepared thermosensitive formulations were evaluated for their physical appearance, drug content, gelation temperature, injectability and rheological properties, in vitro release studies and stability studies. Moreover, cell proliferation assays on human retinal pigment epithelial ARPE-19 cells were performed to evaluate the influence of this innovative system on the cellular viability. In addition, minimal inhibitory concentration (MIC) was assessed for both CEF and dCEF, revealing the need of dCEF hydrolysis for the antimicrobial activity. Although further experimental investigations are required, the physico-chemical characterization of the nanocomposite hydrogels and the preliminary in vitro release studies highlighted the potential of these systems for the sustained release of CEF.

Development and optimization of besifloxacin hydrochloride loaded liposomal gel prepared by thin film hydration method using 32 full factorial design

The objective of this present research work was to develop and optimize a liposomal gel containing a fourth generation fluoroquinolone antibiotic, besifloxacin hydrochloride (BSF−HCl), for ocular delivery using factorial design. The ocular delivery of BSF−HCl loaded liposomal gels may produce improve the ocular bioavailability with increased residence time of drug in the cornea and decreasing the non-productive absorption of besifloxacin hydrochloride. Besifloxacin hydrochloride loaded liposomes were prepared by thin-film hydration technique. The effect of two independent factors (soya lecithin to cholesterol ratio and lipid to drug ratio) on characteristics of liposomes i.e. responses (entrapment efficiency, drug loading and particle size) were examined. A quadratic polynomial model equation was generated to predict the relationship between independent factors and the responses. The in vitro drug release from the optimized liposomes exhibited biphasic release pattern for the initial rapid release and subsequently sustained drug release. The optimized liposomes (F1) were incorporated into a gel containing carbopol 940, tri-ethanolamine and glycerol. The optimized BSF−HCl loaded liposome formulation (F1) showed the encapsulation efficiency, drug loading and particle size of 41.01 ± 1.22%, 10.84 ± 0.46% and 436.8 ± 23.4 nm, respectively. The ex-vivo corneal permeation of the drug loaded liposomal gel demonstrated a significant (p < 0.05) increment of BSF−HCl permeation than the BSF−HCl loaded gel and the histological study on the pig cornea showed no corneal drainage even after 8 h of application. Thus, the developed BSF−HCl loaded liposomal gel could be used as an effective ocular drug delivery system to treat bacterial infections.

Thermosensitive glycol chitosan-based hydrogel as a topical ocular drug delivery system for enhanced ocular bioavailability.

In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 °C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscopy (SEM). H-GCS had minimal in vitro cytotoxicity against L-929 and HCEC cells over a concentration range of 0-0.8 mg/mL. Additionally, the H-GCS hydrogel exhibited good ocular tolerance and biocompatibility after a single instillation. Moreover, H-GCS hydrogel significantly prolonged the precorneal retention of fluorescein sodium compared with its aqueous solution. An in vivo pharmacokinetic study demonstrated that the levofloxacin-loaded H-GCS hydrogel could provide a significantly higher Cmax and AUC0-12h compared with the levofloxacin aqueous solution, thus increasing ocular bioavailability. Overall, the proposed H-GCS hydrogel acts as an in situ gelling system that might represent a promising vehicle for topical ocular drug delivery.

Phenylboronic acid-tethered chondroitin sulfate-based mucoadhesive nanostructured lipid carriers for the treatment of dry eye syndrome

Dry eye syndrome is a common eye disease that affects many people worldwide. It is usually treated with eye drops, which has low bioavailability owing to rapid clearance from the ocular surface and leads to poor patient compliance and side effects. For the purpose of improving the therapeutic efficacy, nanostructured lipid carrier (NLC)-loaded dexamethasone (DEX) was prepared and functionalized with (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS). As APBA has a boronic acid group, it can form a high-affinity complex with sialic acids present in the ocular mucin, which contributes to extension of corneal retention time and improvement of drug delivery. Compared with eye drops, Rhodamine B (RhB)-labeled APBA-ChS-NLC could significantly prolong the residence time on the corneal surface. Moreover, the DEX-APBA-ChS-NLC showed no irritation to the rabbit eye as indicated in irritation studies and histological images. The pharmacodynamics study indicated that DEX-APBA-ChS-NLC could relieve symptoms of dry eye disease in rabbits. These results demonstrated that the developed mucoadhesive drug carrier could improve the delivery of drugs and have promising potential to treat anterior eye diseases. Statement of SignificanceIn this research, (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS)-based nanostructured lipid carriers (NLCs) including dexamethasone (DEX) were designed and constructed. APBA-ChS, which is present on the surface of DEX-NLC and contains the boronic acid group, can form complex with sialic acids in the ocular mucin, hence leading to prolonged precorneal retention. This affinity between boronic acid and sialic acids was used to develop a mucoadhesive drug delivery system. The developed mucoadhesive drug carrier demonstrated prolonged retention time and alleviation of dry eye syndrome. APBA-ChS-based NLC may be considered a promising ocular drug delivery system for treating anterior eye diseases.

Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery.

The effective delivery of drugs to the eye remains a challenge. The eye has a myriad of defense systems and physiological barriers that leaves ocular drug delivery systems with low bioavailability profiles. This is mainly due to poor permeability through the epithelia and rapid clearance from the eye following administration. However, recent advances in both polymeric drug delivery and biomedical nanotechnology have allowed for improvements to be made in the treatment of ocular conditions. The employment of biodegradable polymers in ocular formulations has led to improved retention time, greater bioavailability and controlled release through mucoadhesion to the epithelia in the eye, amongst other beneficial properties. Nanotechnology has been largely investigated for uses in the medical field, ranging from diagnosis of disease to treatment. The nanoscale of these developing drug delivery systems has helped to improve the penetration of drugs through the various ocular barriers, thus improving bioavailability. This review will highlight the physiological barriers encountered in the eye, current conventional treatment methods as well as how polymeric drug delivery and nanotechnology can be employed to optimize drug penetration to both the anterior and posterior segment of the eye.

DEVELOPMENT, EVALUATION AND CHARACTERISTICS OF OPHTHALMIC IN SITU GEL SYSTEM: A REVIEW

Eye is a sensitive organ and is easily injured and infected. Delivery of drugs into eye is complicated due to removal mechanism of precorneal area results decrease in therapeutic response. Conventional ocular delivery systems like solution, suspension, ointment shows some disadvantages such as rapid corneal elimination, repeated instillation of drug and short duration of action. In situ polymeric delivery system will help to achieve optimal concentration of drug at the target site, thereby helps to achieve the desired therapeutic concentration. There are various novel ocular drug delivery systems such as In-situ gel, dendrimers, niosomes, nanoparticulate system, collagen shield, ocular iontophoresis suspension and ocusert etc. In situ gelling systems are liquid upon instillation and undergo a phase transition to form gel due to some stimuli responses such as temperature modulation, change in pH and presence of ions. Various attempts have been made towards the development of stable sustained release in-situ gels. Newer research in ophthalmic drug delivery systems is directed towards an incorporation of several drug delivery technologies, that includes to build up systems which is not only extend the contact time of the vehicle at the ocular surface, but which at the same time slow down the removal of the drug. This is a review based on ocular in situ gels, characteristization, techniques and evaluation of in situ ophthalmic drug delivery systems,

Neem seed oil and gum arabic-based oil-in-water emulsions as potential ocular drug delivery system

The present study deciphers the synthesis and characterization of the neem seed oil (NSO) and gum arabic (GA) based emulsion. The synthesized emulsions were thoroughly characterized for probable application in ocular drug delivery. The synthesized emulsions were white in color. The FTIR spectroscopy divulged that the glycoprotein complex of GA retained its functional architecture. The formation of the oil-in-water emulsion was confirmed by confocal microscopy. The NSO droplets in the emulsions behaved as capacitive elements whose properties altered as the composition of the emulsions were varied. The mechanical studies suggested that the interactions within the emulsion components tailored the polymer-polymer integrity under stress. The drug release and corneal permeation studies using ciprofloxacin HCl-loaded emulsions indicated that the ciprofloxacin molecules were released from the emulsions, and the emulsions were able to deliver the drug across the corneal tissue. The prepared emulsions were nonirritant to the ocular tissues. The released drug was capable of inhibiting the growth of the model bacteria (Staphylococcus aureus). In gist, the prepared emulsions were suitable for ocular drug delivery applications.

A Review of Potential Effect of Nanotechnology and Control Drug Delivery System Introduce Into Ocular Drug Delivery System

A Review of Potential Effect of Nanotechnology and Control Drug Delivery System Introduce Into Ocular Drug Delivery System

Contact Lenses: A Promising Drug Delivery System

Presently, around 100 million people are estimated to be wearing contact lenses, and the number is growing exponentially. Though the main use of contact lenses is for improving ametropia problems, they also hold attention as therapeutic devices for the treatment of ocular pain, promotion of corneal healing, maintenance of corneal epithelial hydration, and drug delivery. Contact lenses are developing as an substitute ophthalmic drug delivery system to resolve the problems of the conventional topical application methods [1,2]. The interest in evolving contact lenses for drug delivery has expressively increased in the last decade as several new techniques have been developed for designing contact lenses for extended drug delivery. The newest studies show that contact lenses are able to achieve prolonged release of a few weeks without any significant effect on critical lens properties. The future appears promising for drug eluting contact lenses but several challenges remain to be overcome regarding processing and storage issues, lack of use in the elderly population, regulatory issues, high costs of clinical studies and cost-benefit analysis[3]. Contact lenses are attractive for ocular drug delivery systems as significantly prolong the residence time of the drug in the eye, high degree of comfort which improve patient compliance, higher efficiency and low side effects and, hence increase the ocular drug bioavailability[16]. Keywords: Lenses, polymer, methods, therapeutic, eye

Formulation and Optimization of Itraconazole Loaded Novel Nanostructured Lipid Carrier-based Ocular Controlled Release Formulation.

Background: The low penetration power and the retention time into the intraocular tissue are the main problems that make difficult for most of the drugs for the ocular drug delivery system. This is for those drugs that are having the low or poor solubility and the low permeability. Objective: Nanostructured Lipid Carriers (NLCs) loaded with Itraconazole (ITZ) were formulated with the aim to increase the solubility and enhance the retention time in the intraocular tissue. Methods: The NLCs were prepared by using Pluronic (PF127), stearic acid and oleic acid. Itraconazole loaded Nanostructured lipid carrier were prepared by high-pressure homogenization method and the formulations were prepared and optimized by 3 Level Factorial Design. Results: F6 was selected on the basis of better entrapment efficiency (94.65), optimum particle size (310nm), and percentage cumulative release (68.67%). Scanning electron microscopy revealed spherical Nanostructured lipid carrier in the microemulsion. Nanostructured lipid carrier Irritation test showed the non-irritancy and antifungal activity showed a more inhibition zone as compared to the marketed formulation. Conclusion: Conclusively the optimized Formulation (F6) shows better results for the ocular drug delivery as compared to the marked formulation.