Ophthalmic Drug Delivery Research Articles

A comprehensive review on nanoemulsion as an ophthalmic drug delivery system

Nanoemulsions formulated for the ocular drug delivery have a good scope in pharmaceutical products due to the transparency at enlarged droplet volume fraction, advanced rate of bioavailability and improved shelf life. They are a part of multiphase colloidal dispersion where a heterogeneous system has fine oil in water or water in oil dispersion in addition with the surfactant and co-surfactant containing droplets within the size range of 20–600 nm and showing a narrow size distribution. This review describes the preparation, characteristics, evaluation and application of nanoemulsions as a drug delivery tool for medication delivery in eyes. The review summarizes in-depth information on the development of ophthalmic nanoemulsions providing sustained release and prolonged therapeutic effect. Various methods comprising of high energy techniques and low energy techniques are discussed in detail. Finally, the techniques for characterization, in-vivo evaluation and applications are deliberated in short.

Ophthalmic Sensors and Drug Delivery

Advances in multifunctional materials and technologies have allowed contact lenses to serve as wearable devices for continuous monitoring of physiological parameters and delivering drugs for ocular diseases. Since the tear fluids comprise a library of biomarkers, direct measurement of different parameters such as concentration of glucose, urea, proteins, nitrite, and chloride ions, intraocular pressure (IOP), corneal temperature, and pH can be carried out non-invasively using contact lens sensors. Microfluidic contact lens sensor based colorimetric sensing and liquid control mechanisms enable the wearers to perform self-examinations at home using smartphones. Furthermore, drug-laden contact lenses have emerged as delivery platforms using a low dosage of drugs with extended residence time and increased ocular bioavailability. This review provides an overview of contact lenses for ocular diagnostics and drug delivery applications. The designs, working principles, and sensing mechanisms of sensors and drug delivery systems are reviewed. The potential applications of contact lenses in point-of-care diagnostics and personalized medicine, along with the significance of integrating multiplexed sensing units together with drug delivery systems, have also been discussed.

Combining modeling of drug uptake and release of cyclosporine in contact lenses to determine partition coefficient and diffusivity

Ophthalmic drug delivery via eye drops is inefficient because only about 1-5% of the drug permeates the cornea during the short residence time of a few minutes. Contact lenses are receiving considerable attention for delivering ophthalmic drugs because of higher bioavailability and the possibility of sustained release from hour to days, and possibly longer. The drug release durations from contact lenses are typically measured in vitro and it is challenging to relate the in vitro release to in vivo release, particularly for hydrophobic drugs which may not exhibit sink release in vitro and in vivo. The in vitro release can be fitted to diffusion equation to determine the partition coefficient and diffusivity, which can then be utilized to model in vivo release. The Higuchi equation is frequently used to model the short time release from a contact lens to determine diffusivity with the implicit assumption that the release is under sink conditions and the starting concentration in the lens was uniform. Both conditions may be violated when measuring release of hydrophobic drugs from contact lenses because the diffusivity and partition coefficient, and also the time needed for equilibrium are not known a priori. Here we develop a method to use the data for both loading and release of cyclosporine, which is a common hydrophobic ophthalmic drug, to determine the partition coefficient and diffusivity. The proposed approach does not require sink conditions and also does not require the lens to be fully equilibrated during loading, which may take almost a month for lenses considered here. The model is based on solving the diffusion equation in the gel along with a mass balance in the fluid. The model equations are solved numerically by finite difference. When the value of partition coefficient is high, such as it is for cyclosporine, the dynamic data is only sensitive to a ratio of partition coefficient and diffusivity, and this ratio had to first be determined from the loading data. Then the two unknown parameters were obtained by minimizing the error between the model prediction and experimental data. The method was used to determine D and K for several silicone hydrogel formulations with varying ratio of hydrogel and silicone fractions.

In vitro and in vivo evaluation of ketotifen-gold nanoparticles laden contact lens for controlled drug delivery to manage conjunctivitis

To overcome the limitations of eye drop solutions, contact lenses are widely used for controlled ophthalmic drug delivery. However, drug-laden contact lenses prepared by traditional soaking technique show poor drug uptake, high burst release, and altered critical lens properties. In the current paper, the effect of gold nanoparticles (GNPs) on ketotifen uptake from the drug-soaking solution and its release kinetics from the lens was investigated. In one method, GNPs solutions of varying strength were loaded into the ketotifen-soaking solution (mM-GNPs-SS batches), and in another method, the GNPs were incorporated in the contact lens during fabrication (mM-GNPs-L batches). The GNPs were spherical, with an average diameter of 17.2 nm and a zeta potential of −21.2 mV. The contact lens's swelling, oxygen permeability, and optical transmittance were improved when compared to lenses prepared by traditional soaking method (K-SM-L). The mM-GNPs-L lenses showed substantial improvement in drug uptake from the ketotifen-soaking solution compared to the K-SM-L and mM-GNPs-SS lenses. The in vitro experiments showed low burst and control ketotifen release up to 96 h, compared to 48 h with the K-SM-L lens. The ability to sustain ketotifen release profile improved proportionally with an increase in the amount of GNPs in the lens. The protein adherence was reduced with the presence of GNPs in the contact lens. The GNPs-laden lenses were found to be safe in ocular irritation and histopathology reports (rabbit model). Further, they showed higher ketotifen retention in the rabbit tear fluid compared to the K-SM-L lens and eye drop solution. Thus, the presence of GNPs in contact lenses increased ketotifen uptake from the soaking solution, reduced burst release, and improved the in vitro and in vivo release kinetics without affecting the critical lens properties for therapeutic application.

Acyclovir-Loaded Nanoemulsions: Preparation, Characterization and Irritancy Studies for Ophthalmic Delivery

ABSTRACT Objective: The main goal of the present work was to develop and evaluate nanoemulsions (NEs) containing acyclovir (ACV) for ophthalmic drug delivery. Method: Firstly, component screening was performed by determining ACV solubility in various oils, surfactants, and co-surfactants. Different NE formulations were developed based on pseudo-ternary phase diagrams, and physicochemical assets were evaluated. Selected formulations were subjected to the drug release efficacy, stability studies, and ex-vivo trans-corneal permeation test. The safety of NEs was investigated by the modified Draize test and hen’s egg test-chorioallantoic membrane (HET-CAM). Results: Based on the solubility studies, Tween 20, Triacetin, and Tramsectol®P were chosen to prepare NE formulations. Developed NEs showed desirable physiochemical properties, including a droplet size of less than 15 nm. Selected formulations (F1 and F2) exhibited a sustained drug release pattern compared to the control group (P < .001). ACV penetration from F1 and F2 to the excised bovine cornea was 2.85 and 2.9-fold more than the control, respectively. Furthermore, HET-CAM and modified Draize test confirmed that F1 and F2 were safe for ocular administration. Conclusion: Present investigation revealed that ACV-loaded NEs could be effective, and safe platform for ophthalmic delivery of ACV.

Thermosensitive Chitosan-β-Glycerophosphate Hydrogels as Targeted Drug Delivery Systems: An Overview on Preparation and Their Applications.

Today, with the advances in technology and science, more advanced drug delivery formulations are required. One of these new systems is an intelligent hydrogel. These systems are affected by the environment or conditions that become a gel, stay in the circumstance for a certain period, and slowly release the drug. As an advantage, only a lower dose of the drug is required, and it provides less toxicity and minor damage to other tissues. Hydrogels are of different types, including temperature-sensitive, pH-sensitive, ion change-sensitive, and magnetic field-sensitive. In this study, we investigated a kind of temperature-sensitive smart hydrogel, which has a liquid form at room temperature and becomes gel with increasing temperature. Chitosan-β-glycerophosphate hydrogels have been researched and used in many studies. This study investigates the various factors that influence the gelation mechanism, such as gel formation rates, temperature, pH, time, and gel specificity. Hydrogels are used in many drug delivery systems and diseases, including nasal drug delivery, vaginal drug delivery, wound healing, peritoneal adhesion, ophthalmic drug delivery, tissue engineering, and peptide and protein delivery. Overall, the chitosan-β-glycerophosphate hydrogel is a suitable drug carrier for a wide range of drugs. It shows little toxicity to the body, is biodegradable, and is compatible with other organs. This system can be used in different conditions and different medication ways, such as oral, nasal, and injection.

Recent Advances in New Copolymer Hydrogel‐Formed Contact Lenses for Ophthalmic Drug Delivery

AbstractPharmaceuticals delivery to the eye sites of interest via the means of contact lenses (CLs) has attracted significant research attention in recent years. Compared with the conventional formulation in eye treatment such as eye drops, CLs administration has shown remarkable advantages in overcoming the challenges involved in ocular drug delivery such as higher bioavailability, longer drug residence and better medication compliance. This review will first detail each of the material components which have been used in the context of CLs, including HEMA, MAA, DMA, NVP, EGDMA, TRIS and PDMS. The pros and cons of each material in tailoring drug release rates of different encapsulated payloads will be discussed, with special focus on their impact on the therapeutic efficiency. In addition, the advancement of recent emerging copolymer CLs hydrogels, originated from these sophisticated monomers with distinct functions, are further summarized into several synthetic strategies in the means of copolymer architecture design and function‐performance relationship in ophthalmic applications. Finally, the possible considerations for future design of multifunctional CLs hydrogels by combing material selection rationales with biological interface science are proposed.

A Novel Drug Delivery System: Review on Microspheres

Microspheres are multiparticulate drug delivery systems that are designed to deliver drugs to a particular location at a fixed rate. Microspheres are free-flowing powders made up of biodegradable proteins or synthetic polymers with particle sizes ranging from 1 to 1000µm. Benefits of the use of microspheres in fields such as drug delivery, bone tissue manufacturing, and the absorption and desorption of contaminants by regeneration. The study shows the method of planning and measurement of microsphere parameters. Microspheres are complex, such as bioadhesive microspheres, polymeric microspheres, magnetic microspheres, floating microspheres, radioactive microspheres. Microspheres may be used in various fields such as cosmetics, oral drug delivery, target drug delivery, ophthalmic drug delivery, gene delivery, and others listed in the study. In order to achieve optimal therapeutic effectiveness, it is important to deliver the agent to the target tissue at an optimum level within the right timeframe, resulting in little toxicity and minimal side effects. There are different approaches to supplying the medicinal drug to the target site in a continuous managed manner. One such strategy is the use of microspheres as drug carriers. In this article, the value of the microsphere is seen as a novel drug delivery carrier to achieve site-specific drug delivery was discussed.&#x0D; Keywords: microspheres, method of preparations, polymer, bioadhesion, types of microspheres

Contact Lenses as Ophthalmic Drug Delivery Systems: A Review.

Ophthalmic drugs used for the treatment of various ocular diseases are commonly administered by eye drops. However, due to anatomical and physiological factors, there is a low bioavailability of the active principle. In order to increase the drug residence time on the cornea to adequate levels, therapeutic contact lenses have recently been proposed. The polymeric support that constitutes the contact lens is loaded with the drug; in this way, there is a direct and effective pharmacological action on the target organ, promoting a prolonged release of the active principle. The incorporation of ophthalmic drugs into contact lenses can be performed by different techniques; nowadays, the soaking method is mainly employed. To improve the therapeutic performance of drug-loaded contact lenses, innovative methods have recently been proposed, including the impregnation with supercritical carbon dioxide. This updated review of therapeutic contact lenses production and application provides useful information on the most effective preparation methodologies, recent achievements and future perspectives.

Rapid Electrochemical Quantification for In Vitro Release Trait of Ophthalmic Drug Loaded within Mucoadhesive Metal Organic Framework (MOF)

AbstractLimited residence time of drugs in the ocular surface, poor bioavailability and side effects are the major challenges in ophthalmic treatment. From the last decade, the pharmaceutical industry is in search of a reliable ophthalmic drug delivery system. In the present study, we demonstrate amine‐functionalized mucoadhesive MIL88B(FeMOF) as a drug delivery cargo to encapsulate ophthalmic drug Timolol (TM) at a rate of 195 μg/mg. Invitro release of TM (only upto 63 %) from loaded FeMOF (TM@FeMOF) within 10 h without burst effect was a noticeable feature that anticipates enhanced preocular retention by the sustained release of TM through extensive H‐bonding of the amine group of MOFs with mucin. A novel and facile approach using Differential Pulse Voltammetry (DPV) were harnessed for rapid quantification of TM during in‐vitro release studies, further validated by HPLC measurement(&lt;10 % deviation). The encouraging results from in‐vitro studies forecast the success story of TM@FeMOF as a biocompatible, biodegradable, and sustainable ophthalmic drug delivery system.

Formulation and release of timolol maleate from ocusert based on gelatin-N-(3-dimethylaminopropyl)-N-ethylcarbodiimide polymer

Context: Glaucoma is a disease of the eyes characterized by an increase in the intraocular pressure. Timolol maleate is commonly used as eye drops for chronic glaucoma treatment. Aims: To formulate an ocusert (novel ophthalmic drug delivery systems) in order to overcome disadvantages of eye drops such as patient’s noncompliance and drainage of the administered solution. Also, to improve treatment outcomes by keeping sustained release of constant amount of timolol maleate and to avoid repeated administration of conventional eye drops. Methods: Timolol maleate ocuserts were formulated using cross-linked gelatin polymer which was prepared using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-hydroxysuccinamide (NHS). Different ocusert formulas were prepared (M1-M17) by varying concentrations of EDC, different temperatures and time for the cross linking as per central composite design. Physicochemical characteristics of drug loaded ocuserts were investigated. Results: Selected formula (M8) exhibited an excellent in vitro drug release results which was extensively evaluated. Fourier transform infrared spectral scan indicates no incompatibility exists between the drug and the polymer used. M8 formula was evaluated in vivo by assessing the eye irritancy, drug release and therapeutic effect when placed in the cul-de-sac of rabbit’s eyes and was compared with conventional eye drops therapy. Conclusions: There was a correlation between in vivo and in vitro release of timolol maleate which is associated with a decrease of glaucoma induced by dexamethasone eye drops in experimental rabbits. The data established the potential of ocusert to improve the therapeutic delivery of timolol maleate and offers a promising option in glaucoma treatment.

Ophthalmic Drug Delivery Systems (Review)

Introduction. Effective delivery of ophthalmic drugs is challenging. The eye has a number of protective systems and physiological barriers, which is why ophthalmic dosage forms have a low bioavailability, usually not exceeding 5 %. Topical drug administration is relatively easy to use and is most commonly prescribed by physicians for the treatment of ophthalmic diseases, especially the anterior segment of the eye. However, when using traditional delivery systems, a number of problems arise: patients' violation of the drug administration technique, and, as a consequence, a decrease in treatment compliance, restriction of drug delivery to the target eye tissues due to low epithelial permeability and rapid clearance after drug administration. Maintaining a constant therapeutic drug level is another challenge that traditional delivery systems often fail to cope with.Text. The article discusses the types of ophthalmic delivery systems. Traditional ones are represented by such dosage forms as eye drops, ointments, gels. Modern ophthalmic dosage forms are represented by: eye films, contact lenses and eye implants. The characteristics, advantages and disadvantages of each type of delivery systems and their promising directions of development, as well as modern developments in this area are given.Conclusion. Currently, most of the scientific research on the development of ophthalmic delivery systems is devoted to obtaining dosage forms capable of maintaining a constant concentration of the drug in the target tissue, providing the transport of active ingredients to them. This is achieved by using modern advances in nanotechnology and polymer chemistry. Receive liquid and soft dosage forms with micro-, nano- and micro-nano-carriers. Polymeric delivery systems such as films, lenses and implants are being actively developed and studied. The development of modern technological approaches opens up new possibilities for the treatment of a wide range of ophthalmic diseases by reducing the side effects often induced by the intrinsic toxicity of molecules, reducing the frequency of the administered dose and maintaining the pharmacological profile of the drug. Thus, the use of modern ophthalmic delivery systems can significantly limit the use of invasive treatments.

Development of an In Vitro Blink Model for Ophthalmic Drug Delivery.

Purpose: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using computer-aided design software and printed using a stereolithography 3D printer. The eyelid and eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min. Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation, nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL) than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05). Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better results than a simple, static vial incubation model.

Development, Optimization, and Antifungal Assessment of Ocular Gel Loaded With Ketoconazole Cubic Liquid Crystalline Nanoparticles.

Ketoconazole is a drug that belongs to azole antifungal group. The current available marketed products of ketoconazole are accompanied with potential drawbacks such as short retention time at the eye surface and eye irritation. The aim of this research is to find a solution for the previously mentioned limitations through loading of ketoconazole within cubosomes (KZ-Cub) to be used as ophthalmic drug delivery systems. Cubosomes properties will help to keep the encapsulated drug in the solubilized form. Further incorporation of cubosomes into biodegradable polymer based gel could prolong the ocular retention time of the drug. Three studied independent variables included glyceryl-mono-oleate, Pluronic-F127 and Polyvinyl alcohol percentage with respect to the dispersion media, while particle size, entrapment efficiency and stability index were the dependent variables that have been evaluated. The optimized cubosomes was assessed for its in-vitro and in-vivo antifungal activity. The prepared gel loaded with KZ-Cub formula had an enhanced permeability, ocular availability, antifungal activity and significant decrease in MIC values compared to commercial one, which reflected the strong impact on the activity of KZ in the management of eye infection.

Betaxolol‐loaded niosomes integrated within pH‐sensitive in situ forming gel for management of glaucoma

Blindness and impaired vision are considered as the most troublesome health conditions leading to significant socioeconomic strains. The current study focuses on development of nanoparticulate systems (i.e., niosomes) as drug vehicles to enhance the ocular availability of betaxolol hydrochloride for management of glaucoma. Betaxolol-loaded niosomes were further laden into pH-responsive in situ forming gels to further extend precorneal retention of the drug. The niosomes were evaluated in terms of vesicle size, morphology, size distribution, surface charge and encapsulation efficiency. The optimized niosomes, comprised of Span® 40 and cholesterol at a molar ratio of 4:1, displayed particle size of 332 ± 7 nm, zeta potential of −46 ± 1 mV, and encapsulation efficiency of 69 ± 5%. The optimal nanodispersion was then incorporated into a pH-triggered in situ forming gel comprised of Carbopol® 934P and hydroxyethyl cellulose. The formed gels were translucent, pseudoplastic, mucoadhesive, and displayed a sustained in vitro drug release pattern. Upon instillation of the betaxolol‐loaded niosomal gel into rabbits’ eyes, a prolonged intraocular pressure reduction and significant enhancement in the relative bioavailability of betaxolol (280 and 254.7%) in normal and glaucomatous rabbits, were attained compared to the marketed eye drops, respectively. Hence, the developed pH-triggered nanoparticulate gelling system might provide a promising carrier for ophthalmic drug delivery and for improved augmentation of glaucoma.

Assessment of In-Situ Gelling Microemulsion Systems upon Temperature and Dilution Condition for Corneal Delivery of Bevacizumab.

Bevacizumab (BVZ), a recombinant humanized monoclonal antibody, has recently been proposed as a topical application in the treatment of anterior segment neovascularization; however, as there are some disadvantages in the administration of common eye-drops, ophthalmic topical drug delivery systems are under study to improve the precorneal residence time, reducing the frequency of administration. In this work, oil-in-water and water-in-oil BVZ-loaded microemulsions are developed, able to increase their viscosity, either by the formation of a liquid-crystalline structure upon aqueous dilution, thanks to the presence of Epikuron® 200 and polysorbate 80, or by body-temperature-induced jellification for the presence of Pluronic® F127 aqueous solution as an external phase. In oil-in-water microemulsion, hydrophobic ion pairs of BVZ were also prepared, and their incorporation was determined by release studies. Microemulsions were characterized for rheological behavior, corneal opacity, in vitro corneal permeation, and adhesion properties. The studied microemulsions were able to incorporate BVZ (from 1.25 to 1.6 mg/mL), which maintained dose-dependent activity on retinal pigment epithelial ARPE-19 cell lines. BVZ loaded in microemulsions permeated the excised cornea easier (0.76–1.56% BVZ diffused, 4–20% BVZ accumulated) than BVZ commercial solution (0.4% BVZ diffused, 5% accumulated) and only a mild irritation effect on the excised cornea was observed. The good adhesion properties as well the increased viscosity after application, under conditions that mimic the corneal environment (from 1 × 103 to more than 100 × 103 mPa·s), might prolong precorneal residence time, proving these systems could be excellent topical BVZ release systems.

Preparation, optimization, and transcorneal permeability study of lutein-loaded solid lipid nanoparticles

To improve the stability and corneal permeability of unstable poorly biocompatible lutein, lutein solid lipid nanoparticles (Lutein-SLNs) were prepared using ultrasonic assisted emulsion evaporation-low temperature curing method and optimized by response surface methodology (RSM). The properties of Lutein-SLNs were evaluated in terms of these encapsulation efficiency, particle size, zeta potential, transmission electron morphology (TEM), and corneal permeability in vitro. The stability and in vitro release behavior of the nanoparticles were also investigated. The optimal formulation was drug: glyceryl monostearate (GM): lecithin high potency (LHP): poloxamer-188 (P-188) = 1: 3.75: 1.78: 2.58 (w/w/w/w), which resulted in particle size, polydispersity index (PDI), encapsulation efficiency and zeta potential of 118.50 ± 1.02 nm, 0.136 ± 0.017, 94.43 ± 1.08% and −25.84 ± 2.45 mV, respectively. Specifically, compared with free lutein, the stability of the Lutein-SLNs against heat, light and oxygen were improved by 4.42-fold, 3.41-fold and 3.21-fold, respectively. Finally, the in vitro release studies revealed that Lutein-SLNs had a good sustained release effect, and in permeation study the apparent permeability coefficient (Papp) of Lutein-SLNs was 1.52-fold greater than free lutein. Therefore, the method used in this study for preparing Lutein-SLNs was an efficient approach, and Lutein-SLNs could increase the transcorneal flux, improve the stability of lutein, and serve as an effective ophthalmic drug delivery system for lutein.

Safety assessment of polymeric micelles as an ophthalmic drug delivery system for intravitreal administration of dasatinib

Background and aimsOcular safety/biocompatibility is an essential element of ophthalmic drug delivery. We previously applied poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-b-PCL) micelles to deliver dasatinib for the management of proliferative vitreoretinopathy (PVR) in vitro. Herein, we seek to ascertain the ocular safety/compatibility of blank and dasatinib loaded PEG-b-PCL micelles, which will set the stage for the future in vivo efficacy evaluations and/or clinical translation for PVR or other eye diseases. MethodsTo access the safety of blank and dasatinib loaded micelles, in vitro cell based assays (LDH cell membrane damage test, SRB cytotoxicity, TEER and permeability of RPE tight junctions), in vivo slit lamp biomicroscopy and optical coherence tomography, Ex vivo histology (H&E staining, GFAP immunofluorescence staining and TUNEL assay) were undertaken. ResultsBoth blank and dasatinib loaded micelles showed remarkable safety profiles at cellular levels. They also caused negligible ocular toxicity/abnormalities up to 28 days post-intravitreal injection in mice. The micelles did not insult the cornea, as demonstrated by slit-lamp biomicroscopy. Ex vivo histology and in vivo optical coherence tomography revealed a normal retinal structure with minimal apoptosis and stresses. ConclusionTaken together, both blank and dasatinib loaded micelles appear to be safe and their applications in drug delivery for eye diseases should be explored.

Design, Optimization, and Characterization of Lactoferrin-Loaded Chitosan/TPP and Chitosan/Sulfobutylether-β-cyclodextrin Nanoparticles as a Pharmacological Alternative for Keratoconus Treatment.

This research study describes the design, optimization, and characterization of two different types of chitosan-based nanoparticles as novel drug delivery systems of a protein drug, lactoferrin. A preclinical consistent base was obtained for both nanosystems, being considered as the first pharmacological treatment for keratoconus as an alternative to current invasive clinical methods. Both types of nanoparticles were obtained via the ionotropic gelation technique. The size and morphology of the nanoparticles were studied as a function of the preparation conditions. A mean size of 180.73 ± 40.67 nm, a size distribution [polydispersity index (PDI)] of 0.170 ± 0.067, and positive ζ-potential values, ranging from 17.13 to 19.89 mV, were achieved. Lactoferrin was successfully incorporated into both types of nanocarriers. In vitro release profiles showed a lactoferrin enhanced, prolonged, and controlled delivery from the polymeric matrix. These formulations also demonstrated no stability or cytotoxicity problems, as well as appropriate mucoadhesive properties, with a high permanence time in the ocular surface. Thus, both types of nanoparticles may be considered as nanocarriers for the controlled release of lactoferrin as novel topical ophthalmic drug delivery systems.

Flexible polymeric nanosized micelles for ophthalmic drug delivery: research progress in the last three years.

The eye is a complex structure with a variety of anatomical barriers and clearance mechanisms, so the provision of safe and effective ophthalmic drug delivery technology is a major challenge. In the past few decades, a number of reports have shown that nano-delivery platforms based on polymeric micelles are of great interest, because of their hydrophobic core that encapsulates lipid-soluble drugs and small size with high penetration, allowing long-term drug retention and posterior penetration in the eye. Furthermore, as an ocular delivery platform, polymeric micelles not only cover the single micellar drug delivery system formed by poloxamer, chitosan or other polymers, but also include composite drug delivery systems like micelle-encapsulated hydrogels and micelle-embedded contact lenses. In this review, a number of ophthalmic micelles that have emerged in the last three years will be systematically reviewed, with a summary of and discussion on their unique advantages or unique drug delivery performance. Last but not least, the current challenges of polymeric micelle formulations in potential clinical ophthalmic therapeutic applications will also be proposed, which might be helpful for future design of ocular drug delivery formulations.