scholarly journals Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 570 ◽  
Author(s):  
Roseline Mazet ◽  
Josias B. G. Yaméogo ◽  
Denis Wouessidjewe ◽  
Luc Choisnard ◽  
Annabelle Gèze
Keyword(s):  
Ocular Surface ◽  
Ex Vivo ◽  
Immunosuppressive Agents ◽  
Delivery Systems ◽  
Ocular Inflammation ◽  
Limiting Factors ◽  
Common Symptom ◽  
Eye Drops ◽  
Colloidal Systems

Ocular inflammation is one of the most common symptom of eye disorders and diseases. The therapeutic management of this inflammation must be rapid and effective in order to avoid deleterious effects for the eye and the vision. Steroidal (SAID) and non-steroidal (NSAID) anti-inflammatory drugs and immunosuppressive agents have been shown to be effective in treating inflammation of the ocular surface of the eye by topical administration. However, it is well established that the anatomical and physiological ocular barriers are limiting factors for drug penetration. In addition, such drugs are generally characterized by a very low aqueous solubility, resulting in low bioavailability as only 1% to 5% of the applied drug permeates the cornea. The present review gives an updated insight on the conventional formulations used in the treatment of ocular inflammation, i.e., ointments, eye drops, solutions, suspensions, gels, and emulsions, based on the commercial products available on the US, European, and French markets. Additionally, sophisticated formulations and innovative ocular drug delivery systems will be discussed. Promising results are presented with micro- and nanoparticulated systems, or combined strategies with polymers and colloidal systems, which offer a synergy in bioavailability and sustained release. Finally, different tools allowing the physical characterization of all these delivery systems, as well as in vitro, ex vivo, and in vivo evaluations, will be considered with regards to the safety, the tolerance, and the efficiency of the drug products.

scholarly journals Polymer-Based Smart Drug Delivery Systems for Skin Application and Demonstration of Stimuli-Responsiveness

Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1285
Author(s):  
Louise Van Gheluwe ◽  
Igor Chourpa ◽  
Coline Gaigne ◽  
Emilie Munnier
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Stimuli Responsive ◽  
Stimuli Responsive Polymers ◽  
Smart Drug ◽  
Smart Drug Delivery

Progress in recent years in the field of stimuli-responsive polymers, whose properties change depending on the intensity of a signal, permitted an increase in smart drug delivery systems (SDDS). SDDS have attracted the attention of the scientific community because they can help meet two current challenges of the pharmaceutical industry: targeted drug delivery and personalized medicine. Controlled release of the active ingredient can be achieved through various stimuli, among which are temperature, pH, redox potential or even enzymes. SDDS, hitherto explored mainly in oncology, are now developed in the fields of dermatology and cosmetics. They are mostly hydrogels or nanosystems, and the most-used stimuli are pH and temperature. This review offers an overview of polymer-based SDDS developed to trigger the release of active ingredients intended to treat skin conditions or pathologies. The methods used to attest to stimuli-responsiveness in vitro, ex vivo and in vivo are discussed.

scholarly journals Potential Effects of Corneal Cross-Linking upon the Limbus

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Johnny E. Moore ◽  
Davide Schiroli ◽  
C. B. Tara Moore
Keyword(s):  
Stem Cells ◽  
Potential Risk ◽  
Ocular Surface ◽  
Ex Vivo ◽  
Uv Exposure ◽  
Cross Linking ◽  
Clinical Complications ◽  
Cellular Dna ◽  
Pathological Consequence

Corneal cross-linking is nowadays the most used strategy for the treatment of keratoconus and recently it has been exploited for an increasing number of different corneal pathologies, from other ectatic disorders to keratitis. The safety of this technique has been widely assessed, but clinical complications still occur. The potential effects of cross-linking treatment upon the limbus are incompletely understood; it is important therefore to investigate the effect of UV exposure upon the limbal niche, particularly as UV is known to be mutagenic to cellular DNA and the limbus is where ocular surface tumors can develop. The risk of early induction of ocular surface cancer is undoubtedly rare and has to date not been published other than in one case after cross-linking. Nevertheless it is important to further assess, understand, and reduce where possible any potential risk. The aim of this review is to summarize all the reported cases of a pathological consequence for the limbal cells, possibly induced by cross-linking UV exposure, the studies donein vitroorex vivo, the theoretical bases for the risks due to UV exposure, and which aspects of the clinical treatment may produce higher risk, along with what possible mechanisms could be utilized to protect the limbus and the delicate stem cells present within it.

scholarly journals Quaternary Ammonium Chitosans: The Importance of the Positive Fixed Charge of the Drug Delivery Systems

2020 ◽  
Vol 21 (18) ◽  
pp. 6617 ◽  
Author(s):  
Angela Fabiano ◽  
Denise Beconcini ◽  
Chiara Migone ◽  
Anna Maria Piras ◽  
Ylenia Zambito
Keyword(s):  
Drug Delivery ◽  
Quaternary Ammonium ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Fixed Charge ◽  
Innovative Drug ◽  
Natural Polysaccharide ◽  
The Impact

As a natural polysaccharide, chitosan has good biocompatibility, biodegradability and biosecurity. The hydroxyl and amino groups present in its structure make it an extremely versatile and chemically modifiable material. In recent years, various synthetic strategies have been used to modify chitosan, mainly to solve the problem of its insolubility in neutral physiological fluids. Thus, derivatives with negative or positive fixed charge were synthesized and used to prepare innovative drug delivery systems. Positively charged conjugates showed improved properties compared to unmodified chitosan. In this review the main quaternary ammonium derivatives of chitosan will be considered, their preparation and their applications will be described to evaluate the impact of the positive fixed charge on the improvement of the properties of the drug delivery systems based on these polymers. Furthermore, the performances of the proposed systems resulting from in vitro and ex vivo experiments will be taken into consideration, with particular attention to cytotoxicity of systems, and their ability to promote drug absorption.

scholarly journals Development and Characterization of Potential Ocular Mucoadhesive Nano Lipid Carriers Using Full Factorial Design

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 682
Author(s):  
Eszter L. Kiss ◽  
Szilvia Berkó ◽  
Attila Gácsi ◽  
Anita Kovács ◽  
Gábor Katona ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Harmful Effect ◽  
Cell Junctions ◽  
Toxicity Tests ◽  
Eye Drops ◽  
Corneal Toxicity ◽  
Penetration Tests ◽  
Full Factorial

Generally, topically applied eye drops have low bioavailability due to short residence time and low penetration of the drug. The aim of the present study was to incorporate dexamethasone (DXM) into nano lipid carriers (NLC), which contain mucoadhesive polymer, in order to increase the bioavailability of the drug. A 23 factorial experimental design was applied, in which the three factors were the polymer, the DXM, and the emulsifier concentrations. The samples were analyzed for particle size, zeta potential, polydispersity index, and Span value. The significant factors were identified. The biocompatibility of the formulations was evaluated with human corneal toxicity tests and immunoassay analysis. The possible increase in bioavailability was analyzed by means of mucoadhesivity, in vitro drug diffusion, and different penetration tests, such as in vitro cornea PAMPA model, human corneal cell penetration, and ex vivo porcine corneal penetration using Raman mapping. The results indicated that DXM can be incorporated in stable mucoadhesive NLC systems, which are non-toxic and do not have any harmful effect on cell junctions. Mucoadhesive NLCs can create a depot on the surface of the cornea, which can predict improved bioavailability.

scholarly journals Establishing in vitro and in vivo Co-culture Models of Staphylococcus epidermidis and Enterococcus faecalis to Evaluate the Effect of Topical Fluoroquinolone on Ocular Microbes

2021 ◽  
Vol 8 ◽  
Author(s):  
Han Woo Kim ◽  
Jiyeun Kate Kim ◽  
Indal Park ◽  
Sang Joon Lee
Keyword(s):  
Enterococcus Faecalis ◽  
Staphylococcus Epidermidis ◽  
Ocular Surface ◽  
Eye Drops ◽  
Culture Model ◽  
Color Detection ◽  
Culture Models

Purpose: To establish in vitro and in vivo ocular co-culture models of Staphylococcus epidermidis and Enterococcus faecalis and to study how various concentrations of moxifloxacin affect the survival of these two endophthalmitis-causing bacteria.Methods: Standard strains of S. epidermidis and E. faecalis were used. Color detection agar plates were employed to distinguish their colonies. To establish the in vitro and in vivo co-culture models, S. epidermidis and E. faecalis were co-cultivated at different ratios for various periods. For the in vivo model, various volumes and concentrations of either a mono-culture or co-culture were inoculated into the lower conjunctival sac of rabbits. Finally, the newly developed in vitro and in vivo co-culture models were subjected to the moxifloxacin treatment to access its effect on S. epidermidis and E. faecalis.Results: When S. epidermidis and E. faecalis were cultured separately in tryptic soy broth, their growth peaked and plateaued at approximately 16 and 6 h, respectively. When they were co-cultured, the growth peak of S. epidermidis got delayed, whereas the growth peak of E. faecalis did not change. The number of E. faecalis was significantly higher in the co-culture than that in the mono-culture. Treatment with moxifloxacin in the in vitro co-culture model rapidly decreased the number of S. epidermidis cells at doses ≥ 0.125 μg/ml. In contrast, the number of E. faecalis did not change significantly up to 16 μg/ml moxifloxacin. In in vivo co-culture (at 1:1), the S. epidermidis count decreased in a pattern similar to that seen in in vivo mono-culture and was barely detectable at 24 h after inoculation. In contrast, the of E. faecalis count increased up to 16 h and then decreased. When moxifloxacin was applied (zero, one, or two times) to this model, the S. epidermidis count decreased in proportion to the number of treatments. In contrast, the E. faecalis count increased with moxifloxacin treatment.Conclusions: The in vitro and in vivo co-culture models of S. epidermidis and E. faecalis were established to determine the influence of moxifloxacin eye drops on these bacteria. The results clearly show that the moxifloxacin eye drops can make E. faecalis dominant on the ocular surface.

scholarly journals Development of novel bioadhesive niosomal formulation for the transcorneal delivery of moxifloxacin hydrochloride in the treatment of corneal ulcer

2019 ◽  
Vol 10 (3) ◽  
pp. 1874-1882
Author(s):  
Manoj K ◽  
Suhail K
Keyword(s):  
Retention Time ◽  
Bacterial Infections ◽  
Contact Lenses ◽  
Corneal Ulcer ◽  
Ex Vivo ◽  
Eye Drops ◽  
Sustained Drug Release ◽  
Major Drawback ◽  
Duration Of Action

A corneal ulcer is an open sore or epithelial defect with an inflammation of the cornea of the eye. Most of the corneal ulcers are caused by bacterial infections and are common in people who wear contact lenses. Moxifloxacin eye drops are frequently used for the treatment of infectious ulcers. However such formulations have a major drawback, that is the short duration of action and usually, require 4-6 times installation daily. A bioadhesive polymer coated niosomal formulation of moxifloxacin was purposed to show a longer retention time on eyes and subsequent reduction in dosing frequency. Niosomes were prepared by solvent injection method using cholesterol and span 60. The coating of the niosomes was done using Carbopol 934or HPMC as a bioadhesive polymer. The mean particle size of bioadhesive niosomes found to be below 200nm. Optimization of the coating was based on in vitro diffusion studies, ex vivo transcorneal permeation studies and bioadhesion studies. The retention time of the formulation was determined by in vitro and ex vivo bioadhesion testing. The antimicrobial assay confirmed the potency of the formulation against the gram-negative organism. The current study revealed that bioadhesive niosomal formulations have longer corneal retention time and have sustained drug release for a period of 24 hours.

scholarly journals Extended levobunolol release from Eudragit nanoparticle-laden contact lenses for glaucoma therapy

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Navneet Kumar ◽  
Rohan Aggarwal ◽  
Meenakshi K. Chauhan
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Contact Lens ◽  
Contact Lenses ◽  
Ex Vivo ◽  
Eye Drops ◽  
Equilibrium Swelling ◽  
Drug Solution

Abstract Background Majorly, the reason for the permanent loss of vision is glaucoma. But the currently available common treatment methodologies such as eye drops have various disadvantages like patient incompliance due to repeated administration and poor (1–5%) bioavailability leading to poor efficiency. The objective of this research was to formulate Eudragit-based nanoparticles of levobunolol incorporated into a contact lens to obtain sustained ocular delivery of levobunolol at the therapeutics level. Eudragit nanoparticles of levobunolol were formulated by nanoprecipitation methodology utilizing different ratios of Eudragit S100 and polyvinyl alcohol. The prepared nanoparticles were evaluated and optimized by efficiency of entrapment, particle size, morphology of surface and zeta potential. The optimized nanoparticles were then entrapped into the matrix of the contact lens by the soaking method which were then characterized and compared for optical clarity study, equilibrium swelling study, shelf life and in vitro drug release in simulated tear fluid followed by ex vivo transcorneal permeation study. Results Formulation F3 was obtained as optimized nanoparticle formulation with 102.61 nm ± 3.92 of particle size, − 22.2 mV ± 2.76 of zeta potential and 86.995% ± 1.902 of efficiency of entrapment. The equilibrium swelling index and transmittance of nanoparticle incorporated into contact lenses showed better results when compared to drug solution-loaded lenses. In vitro release indicated more sustained drug profiles (84.33% ± 0.34 of drug release over a period of 12 days) as compared to drug solution-loaded lenses (89.282% ± 0.900 of drug release over a period of 3 days). Ex vivo transcorneal permeation studies showed more permeation (6.75% ± 0.170) through contact lenses as compared to marketed eye drops (3.03% ± 0.088). Conclusion This research demonstrates the remarkable results of drug-laden contact lenses to serve as a great medium for the continued delivery of ocular drugs without affecting the physical and optical characteristics of the lens content.

Fabrication and Characterization of Ocular Phase Transition Systems for Blepharitis: A Novel Approach

2020 ◽  
Vol 10 (1) ◽  
pp. 24-37
Author(s):  
Deepali Verma ◽  
Shreya Kaul ◽  
Neha Jain ◽  
Upendra Nagaich
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Eye Drops ◽  
Stability Studies ◽  
In Vitro Drug Release ◽  
In Situ Gel ◽  
Drug Content ◽  
Erythromycin Estolate

Introduction: In the present research, erythromycin estolate loaded in-situ gel was formulated and evaluated for blepharitis in order to improve its therapeutic efficacy, precorneal residence time of the system and to enhance the ocular bioavailability. Material and Methods: The developed formulation was characterized by several parameters viz. FTIR, clarity, pH, gelation temperature, rheological studies, drug content, in vitro drug release studies, transcorneal permeation studies, bioadhesion studies, isotonicity and stability studies. Results: The optimized formulation exhibited non-fickian release diffusion with a sustained release of drug 82.76 ± 0.94% up to 8h and drug content 93.64%. Isotonicity revealed that the formulation was isotonic in nature and there was no shrinkage and busting of cells. Bioadhesion study was performed to check the adherence of the prepared in situ gel to the corneal surface for 4h. Ex vivo transcorneal permeation was observed to be significantly higher when compared with market eye drops. Histopathological studies were conducted to confirm the presence of normal ocular surface tissues by maintaining their morphological structures without causing damage to the tissues. The formulation was nonirritant as confirmed by the HET-CAM test. Stability studies and accelerated stability studies were conducted for 13 weeks and 26 weeks respectively and formulations were analyzed for the visual appearance, pH, viscosity, gelling capacity, drug content and in vitro drug release and results showed no change in the formulations. Conclusion: The formulation was therapeutically efficacious, sterile, stable and provided controlled release over a period of time. The developed system could be a viable alternative to conventional eye drops for treatment of various ocular diseases.

Vildagliptin plasticized hydrogel film in the control of ocular inflammation after topical application: study of hydration and erosion behaviour

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Souvik Nandi ◽  
Abinash Ojha ◽  
Ashirbad Nanda ◽  
Rudra Narayan Sahoo ◽  
Rakesh Swain ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Rabbit Model ◽  
Ocular Inflammation ◽  
Polyethylene Glycol 400 ◽  
Dipeptidyl Peptidase 4 ◽  
Hydrogel Film ◽  
Hydrogel Matrix ◽  
Anti Inflammatory ◽  
Film Formulation

Abstract Vildagliptin (VID) is a dipeptidyl peptidase-4 (DPP-4) inhibitor used in controlling blood glucose level in type 2 diabetes. Vildagliptin improves beta cells function and is also suggested to effectively control the inflammation. The possible ocular anti-inflammatory property of vildagliptin has been explored using topically applied plasticized ocular film formulation. Film formulation was prepared by solvent cast and evaporation method using triethanolamine (TEA), dimethyl sulphoxide (DMSO), and polyethylene glycol 400 (PEG 400) as the plasticizer in HPMC hydrogel matrix base. Anti-inflammatory study was carried out in the carrageenan induced ocular rabbit model. Analytical methods confirmed that the drug was present almost in completely amorphized form in the film formulation. Level of hydration, swelling and erosion rate of the film played the controlling factor in the process of drug release, ocular residence and permeation. Maximum swelling rate of 363 h−1 has been shown by VHT compared to other formulation of VHD and VHP (174 and 242 h−1 respectively). Film containing DMSO exhibited highest in vitro release as well as ex vivo ocular permeation. Film formulation has shown a fast recovery of ocular inflammation in contrast to the untreated eye after inducing inflammation. Plasticized vildagliptin hydrogel film formulation could be utilized in the management and control of ocular inflammation particularly with diabetic retinopathy after proper clinical studies in higher animal and human individuals.

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