Crosslinking-Dependent Drug Kinetics in Hydrogels for Ophthalmic Delivery

Drug-diffusion kinetics in 2-hydroxyethyl methacrylate hydrogels were studied as a function of the crosslinking density and porosity. By varying the concentration of the crosslinker, tetraethylene glycol dimethacrylate, we demonstrated how the release of Timolol maleate could be optimized to allow for efficient drug delivery. FTIR and spectrophotometry supplied optical inferences into the functional groups present. By studying the swelling and degradation of hydrogels, supplemented with drug-release kinetics studies, the relationship between these two tenets could be formulated.

Sorafenib Repurposing for Ophthalmic Delivery by Lipid Nanoparticles: A Preliminary Study

Uveal melanoma is the second most common melanoma and the most common intraocular malignant tumour of the eye. Among various treatments currently studied, Sorafenib was also proposed as a promising drug, often administered with other compounds in order to avoid resistance mechanisms. Despite its promising cellular activities, the use of Sorafenib by oral administration is limited by its severe side effects and the difficulty to reach the target. The encapsulation into drug delivery systems represents an interesting strategy to overcome these limits. In this study, different lipid nanoparticulate formulations were prepared and compared in order to select the most suitable for the encapsulation of Sorafenib. In particular, two solid lipids (Softisan or Suppocire) at different concentrations were used to produce solid lipid nanoparticles, demonstrating that higher amounts were able to achieve smaller particle sizes, higher homogeneity, and longer physical stability. The selected formulations, which demonstrated to be biocompatible on Statens Seruminstitut Rabbit Cornea cells, were modified to improve their mucoadhesion, evaluating the effect of two monovalent cationic lipids with two lipophilic chains. Sorafenib encapsulation allowed obtaining a sustained and prolonged drug release, thus confirming the potential use of the developed strategy to topically administer Sorafenib in the treatment of uveal melanoma.

Development and Optimization of Chitosan-Hydroxypropyl Methylcellulose In Situ Gelling Systems for Ophthalmic Delivery of Bupivacaine Hydrochloride

The aim of this study was the development and optimization of chitosan and hydroxypropyl methylcellulose (HPMC) in situ gelling systems, loaded with bupivacaine hydrochloride for topical ocular administration. This study is based on the properties of two polymers: chitosan, which has mucoadhesive action and is a pH-sensitive polymer, but also the cellulose derivative hydroxypropyl methylcellulose, a thermosensitive polymer which has mucoadhesive properties and increases the viscosity of systems. The analysis and optimization of in situ gelling systems were performed based on an experimental design and response surface methodology. The following formulation parameters were considered: X1 = chitosan concentration (0.5%, 1%), X2 = HPMC E 5 LV concentration (2%, 5%) and X3 = Chitosan/HPMC E 5 LV ratio (1/1, 2/1). In addition, the parameters to be optimized were represented by the contact angle (CA (°)), viscosity and cumulative percentage of bupivacaine hydrochloride released in vitro. The results indicate that the designed in situ gelling systems are suitable for bupivacaine prolonged ophthalmic release and overcome the principal disadvantages of the liquid’s ocular formulations. An immediate therapeutic effect corresponding to ocular anesthetic installation was assured in the first stage: burst bupivacaine release. In the second phase, the gradual drug release was assured for over 6 h. This drug release profile, together with the corresponding rheological profile and a collection of superficial properties for good ocular adhesion balanced with an adequate hydrophilic character, assured the desired quality of the attributes for the proposed systems. The system, based on chitosan 1%, HPMC E 5 LV 5% and a 1/1 polymer ratio, could be a solution for the proposed formulation of in situ gelling colloidal systems, since the viscosity of the system was within the range of the optimal viscosity of the eye, and the amount of bupivacaine hydrochloride released after 6 h was the highest at 69.55%.

Ophthalmic Delivery of Riboflavin Loaded Nanoparticulate Suspension in Keratoconus: A Preclinical Study in Rabbit Model

The present investigation undertakes the formulation of nanoparticulate suspension of Riboflavin to treat keratoconus disease by applying it to the infected mice corneas. The nanoparticles of Riboflavin were prepared using single solvent evaporation method and later formulated as suspension using continuous probe sonication method. Then, both riboflavin nanoparticles and suspension were evaluated for various parameters. The nanoparticles showed smooth and spherical surface with in vitro drug release up to 77.89%. The drug content was found to be 97.23%–98.89%. The suspension was found to be visually clear with pH ranging from 6 to 7. The drug entrapment was found to be from 76.37% to 97.34%. Since there was no hemolytic activity, this formulation was suitable for ophthalmic administration. The Draize test confirmed the non-irritant, non-itchy nature of formulation. The prepared formulations, such as nanoparticulate gel and suspension, were found to be significantly efficacious in experimental animals.

In Situ Gels of Acylovir Nanoemulsions For Improved Delivery to The Eye

Background: Acyclovir, BCS Class III drug is commercially available as 3 % w/w eye ointment for multiple applications. Acyclovir nanoemulsions can be proposed to reduce dose because of improved permeation characteristics. Further, the development of in situ ophthalmic gels can be advantageous to reduce the number of applications due to increased mucoadhesion and sustaining effect. Objective: The purpose of this study was the development and evaluation of nanoemulsions based in situ gels of Acyclovir (1% w/w) as potential ophthalmic delivery systems. Methods: Nanoemulsions of Acyclovir were developed by Phase Inversion Temperature method using Capmul MCM, stearyl amine and Kolliphor RH 40 as liquid lipid, charge inducer and surfactant, respectively selected on the basis of Acyclovir solubility studies in the oil phase and emulsification ability of surfactants. These nanoemulsions were further developed into in situ ophthalmic gels using gellan gum and Methocel K4M. Results: The developed gels showed a sustained effect in vitro release studies and improved goat corneal permeation in ex vivo studies when compared to marketed ointment. HET-CAM studies concluded the absence of irritation potential, while in vivo irritation study in Wistar rats showed the absence of erythema and swelling of eyes after visual inspection for 72 hours. Histopathological studies on isolated rat corneas showed no abnormalities in anterior corneal epithelium and corneal stroma without any epithelial hyperplasia. Acyclovir nanoemulsions based in situ ophthalmic gel showed increased corneal deposition and permeation in rat eyes. Conclusion: The improved potential of developed ophthalmic gels was proven due to the reduced frequency of application compared to the marketed ointment in animal studies.

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 12 h 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.