Ocular Irritation Test Research Articles

Ocular Tolerability and Efficacy of Ebastine Colloidal Formulation in Allergic Conjunctivitis

Allergic conjunctivitis (AC), defined by ocular itching, hyperemia, lacrimation and edema, impairs the quality of life across the globe. Ebastine is available as an oral antihistamine formula, such as tablets and syrup, for allergic disorders. Topical antihistamines are preferred over oral agents since their direct application at the site of action results in rapid onset and superior efficacy with less systemic side effects. The objective of the present work was to evaluate the antiallergic potential of optimized ebastine (1% w/v) colloidal ocular formulation by performing in vitro study like hen's egg chorioallantoic membrane test (HET-CAM) for tolerability and in vivo efficacy study in ovalbumin (OA)-induced allergic conjunctivitis (AC) with acute ocular irritation study. Eye scratching behavior and edema were evaluated after topical antigen challenge. Edema was scored at periodic interval after the instillation of ovalbumin followed by histopathology. The results showed that ebastine (1% w/v) colloidal ocular formulation was effective in inhibiting symptoms of eye inflammation induced by ovalbumin. Further, the study indicated that said formulation has a quick onset and the duration of effect sufficient to provide relief from symptoms for 24 hr. Ocular irritation by HET-CAM assay showed that the developed formulation does not cause any irritation to the blood vessels. Acute ocular irritation test was performed using rabbits and results showed that developed formulation was non-irritant to the eye. The present study revealed that the ocular ebastine formulation could offer a novel therapeutic opportunity against IgE-mediated allergic conjunctivitis.

Brinzolamide–loaded nanoemulsions: ex vivo transcorneal permeation, cell viability and ocular irritation tests

The aim of this study was to investigate the corneal penetration of brinzolamide (BZ) nanoemulsions (NEs) and evaluate their in vitro and ex vivo irritancy potential. Twelve BZ NEs were prepared by the spontaneous emulsification method and ex vivo permeability studies were conducted using excised bovine corneas fixed onto Franz diffusion cells. To confirm the safety of the formulations for ophthalmic use, preparations were examined for potential ocular irritancy using a cell viability assay on retinal cells, the Hen's Egg Test-Chorio-Allantoic Membrane (HET-CAM) and the bovine corneal opacity-permeability (BCOP) test. Seven BZ NEs exhibited superior penetration across isolated bovine cornea compared to the marketed BZ suspension. The half maximal inhibitory concentration (IC50) values of various surfactants and oils determined using the sulforhodamine B cell viability assay on retinal cells showed that Transcutol P, Cremophor RH40 and Triacetin were the least toxic excipients and may be safely used in the eye at various concentrations. HET-CAM and BCOP tests revealed that NE6B and NE4C did not result in any irritation and were thus considered safe for ocular use. Our finding suggests that optimized NEs can be a safe and effective vehicle for ocular delivery of BZ.

Entrapment of drug-sorbate complex in submicron emulsion: A potential approach to improve antimicrobial activity in bacterial corneal infection

Aim of this work was to improve precorneal retention and evaluation of antimicrobial activity of positively charged submicron emulsion (SE) contained ciprofloxacin in ion paired form. Ciprofloxacin (CF) ion-paired with potassium sorbate (PS) expected to increase the lipophilicity and entrapment of CF in the lipid phase of SE, surface of SE droplets was positively charged by chitosan (CN). In-vitro MIC value 0.0687 ± 0.002 (staphylococcus aureus) and 0.0775 ± 0.004 (pseudomonas aeruginosa) for SE-CN-CF-PS and 0.195 ± 0.02 (staphylococcus aureus) and 0.401 ± 0.03 (pseudomonas aeruginosa) for control. The ocular irritancy test was performed using HET-CAM. Entrapment of CF improved, the release was prolonged and AMA enhanced. HET-CAM results with no irritation. Thus, it can be concluded that the SE of CF-PS complex in which surface was charged positively may hold some promise in ocular delivery for severe infections.

FABRICATION OF BIOADHESIVE OCUSERT WITH DIFFERENT POLYMERS: ONCE A DAY DOSE

Objective: The objective of this current study is to fabricate ocuserts to control the drug release from chosen bioadhesive polymeric matrixes to enhance patient compliance. Ciprofloxacin HCl (CFX HCl) was selected as a model drug.Methods: Different bioadhesive polymers with different film forming capabilities namely Hydroxy Propyl Methyl Cellulose (HPMC K4M), Poly Vinyl Alcohol (PVA), Sodium Carboxy Methyl Cellulose (Na CMC), Hydroxy Propyl Cellulose (HPC), Sodium Alginate (Na Alg.), pullulan and Xanthan Gum (XG) in different ratios were used in fabricating ocuserts using solvent-casting technique. Propylene Glycol (PG) was used as a plasticizer to facilitate the fabrication process. Characterization tests of the developed ocuserts were performed as well as bioadhesive tests and in vitro release studies of the incorporated drug. The obtained results were analysed using different release kinetic models. Stability of the selected ocuserts was investigated at 40±0.5 °C and 75±5% Relative Humidity (RH) for three months’ storage period. In vivo ocular irritation test was performed to investigate the safety of the formula in rabbits’ eyes as well as to test the release profile and thus to estimate In vitro In vivo correlation.Results: All the prepared ocuserts showed the uniformity of film characterization and bioadhesion strength ranged from 240±66 and 158±52dyne/cm2. Selected formula from the in vitro release study tested for in vivo study showed the slow release of ciprofloxacin drug up to 24 h with no signs of eye irritancy. Results for In vitro In vivo correlation showed an excellent correlation with R2 value of 0.9982.Conclusion: PVA based ocuserts proven to be a promising once-daily, effective and safe ocular delivery system of the drug.

ANTIOXIDANT ACTIVITY TEST OF THE RED YEAST RICE EXTRACT AND THE FORMULATION IN A CREAM PREPARATIONS ANDIT’S PENETRATION AND SAFETY TEST AT RABBIT

Red yeast rice is one of thefoodstuff that contains flavonoid compounds which are useful as natural antioxidants. One attempt to overcome wrinkles is with antioxidants. The easy way to apply red yeast rice can be make in an extract that are formulated in cream preparations. This study aims to determine the antioxidant activities of Red yeast rice extract and its formulation in cream dosage form and the test of penetration and safety. Red yeast rice extract obtained by the method of maseration using ethanol 96% as a solvent. The cream is make in 3 formula, where the first formula as a negative control, second formula is cream of red yeast rice extract and third formula is cream of red yeast ricemicroemulsion. The antioxidant activity tested by DPPH method, the penetrationstrengthtested by Franz difussionmethod and the safety by primary and ocular irritation test.Research results demonstrated that red yeast rice extract had activity as antioxidant with the IC50 value was 2,60 ppm < 50 ppm (strong antioxidant) and microemulsion cream had penetrationstrength greater than red yeast rice extractcream. And the results of the primary irritation test showed that the cream is very little irritate and the results of the ocular irritation test cream does not irritate the eyes.

FORMULATION DEVELOPMENT AND EVALUATION OF pH TRIGGERED IN SITU OPHTHALMIC GEL OF BESIFLOXACIN HYDROCHLORIDE

The aim of the present work was to formulation and evaluation of pH Triggered in-situ Ophthalmic Gel of Besifloxacin Hydrochloride to overcome the drawbacks obtained by conventional eye drop. There are two independent variables were used i.e. Carbopol 934 and HPMC K100. Carbopol 934 were used as gelling agent and HPMC K100 were used as bioadhesive polymer. Besifloxacin Hydrochloride shows activity against a wide range of Gram-positive and negative ocular pathogens: examples are Corynebacterium pseudodiphtheriticum, Moraxella lacunata, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae and Streptococcus salivarius. The in situ gelling system involves sol-to-gel transition in the cul-de-sac upon instillation to avoid pre corneal elimination. The formulations were prepared by 32 factorial design. The prepared formulations were evaluated for clarity, pH, viscosity, Bioadhesive strength of gel, gel strength gel, Drug Content, In-vitro Drug Release Study, Antibacterial Activity, Isotonicity Evaluation, HET-CAM Test and stability studies. The drug content was in the range of 97-99.57 %. Formulation F5 selected as optimized on the basis of evaluation. It shows highest drug release upto 8hrs. It shows good antibiotic activity against Staphylococcus aureus. The optimized formulation was isotonic with blood cells. It passes sterility test. The optimized formulation passes the ocular irritancy test i.e. HET-CAM Test. The formulation kept for the stability study for 3 months. Short term stability study indicates that room temperature 400±20 was appropriate storage condition for formulations.
 Keywords: pH Triggered, bioadhesive polymer, Carbopol 934, HPMC K100, HET-CAM Test, Antibacterial Activity.

Novel hydrogel-based ocular drug delivery system for the treatment of conjunctivitis.

Conventional dosage form like eye drops showed poor therapeutic response and also require frequent dosing. Therefore, developing the dosage form to deliver the drug to the target site without much loss of drug or without causing any systemic side effects is the challenging job for the researchers in pharmaceutical industries. The main aim of the present work was to formulate and evaluate hydrogel-based drug delivery containing combination of neomycin sulphate and betamethasone sodium phosphate in order to provide prolonged release and also better bioavailability of drugs for the treatment of eye infections. In this study, poloxamer 407 and chitosan at different concentrations were used as the gelling agents. The prepared formulations were evaluated for clarity, pH, drug content, gelling capacity, gelling temperature and in vitro drug release study. From the preliminary studies, F5 formulation was selected as an optimized formulation. The optimized formulation was further evaluated for ex vivo permeation study, sterility test, HET-CAM and ocular irritation testing using rabbits. Ocular irritation by HET-CAM assay showed that the formulated gel does not cause any irritation to the blood vessels. Draize irritation test was performed using rabbits and results showed that formulation was non-irritant to the eye. The formulated hydrogel formulation can be used as an alternative to conventional ophthalmic eye drop formulation of drugs neomycin and betamethasone for the purpose of providing prolonged therapy for the treatment of conjunctivitis.

Nanostructured lipid carriers-based thermosensitive eye drops for enhanced, sustained delivery of dexamethasone.

Nanostructured lipid carriers in-gel (NLCs-gel) were prepared to enhance and improve the ocular delivery of dexamethasone.Materials & methods: NLCs containing dexamethasone prepared by high-pressure homogenization were characterized and dispersed into thermosensitive gels (Pluronic F127 and F68 as gels material). In vitro drug release studies, ocular irritation tests, ex vivo corneal penetration and drug dynamics of NLCs and NLCs-gel were evaluated in aqueous humor. NLCs-gel exhibited a rapid sol-gel transition at 34.4°C and presented nano-sized, narrowly distributed particles. Corneal penetration studies revealed steady sustained drug release (Ritger-Peppas); NLCs-gel increased ocular bioavailability by prolonging precorneal retention time and improving corneal permeation. These findings suggest developing NLCs-gel for potential treatment of posterior segment eye diseases.

Ocular Retention and Bioavailability Studies of Bromfenac Mucoadhesive Nanoparticles by Sustained Ophthalmic Delivery

The present study was designed to formulate the sustained ocular delivery of bromfenac loaded mucoadhesive chitosan nanoparticles (NPs). The NPS were prepared by different ratios of chitosan and sodium alginate by ionic gelation method. The prepared nanoparticles were characterized by its particle size, zeta potential, entrapment efficiency, in vitro release and ocular irritation test. The NPs are employed for transcorneal permeation and in vivo evaluation was carried out in rat eye for ocular toxicity studies. The pharmacokinetic data of selected NPs were compared with marketed bromfenac formulation (Megabrom). The selected NPs were characterized by their mean particle size 202±2.02 nm, encapsulation efficiency 73.4±1.25 % and zetapotential +32.3±0.12 mV. In vitro release exhibited biphasic drug release profile with initial burst followed by slow drug release. The NPs exhibited significant mucin adhesion. The Draize's test showed that, there was no irritation upon topical instillation of prepared NPs. The AUC (0‐α) of NPs was increased up to 4.02 fold and clearance was decreased up to 5.5 fold as compared to marketed ophthalmic formulation and were found to be safe in histopathological studies. It is concluded that he formulated bromfenac NPs showed prolong ocular residence and reducing dosing frequency.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Covalently Cross-Linked Chitosan Hydrogel Sheet for Topical Ophthalmic Delivery of Levofloxacin.

In the present study, a covalently cross-linked chitosan hydrogel sheet was fabricated and assessed as an ophthalmic carrier for topical delivery of levofloxacin. Upon mixing 4-arm polyethylene glycol with aldehyde end groups (4-arm PEG-CHO) with glycol chitosan (GC) at various feed ratios, a series of hydrogel sheets formed spontaneously under mild conditions. Rheological characterization illustrated that the gelation time and moduli of the hydrogels could be tuned by controlling the component concentrations. The swelling ratio of hydrogels increased with decreasing 4-arm PEG-CHO and GC concentrations. The proposed hydrogel exhibited a typical porous structure, with pore size in the range 20-150 μm. This structure allowed the encapsulated levofloxacin to be released from the hydrogel matrix via diffusion within the first 0.5 h, followed by a sustained release up to 24 h. In vitro cytotoxicity and biocompatibility assays showed that the proposed hydrogels are relatively noncytotoxic and have excellent cytocompatibility with L-929 cells after 24 h of incubation. Furthermore, an ocular irritation test demonstrated the non-irritant character of the proposed hydrogel after topical application. These characteristics support the potential use of covalently cross-linked chitosan hydrogel sheets in topical ophthalmic drug delivery applications.

NON-IONIC SURFACTANT VESICLES (NIOSOMES) BASED NOVEL OPHTHALMIC FORMULATION OF TIMOLOL MALEATE

The objective of the present work was to develop drug loaded niosomal ophthalmic formulation of timolol maleate (an antiglaucomal drug) for enhanced trans-corneal drug permeation and better ocular bioavailability. Timolol loaded niosomes were prepared by thin film hydration method using rotary evapoarator and ultra-sonicated for size reducation using probe sonicator. The nano-vesicle (niosomal) formulation was optimized by selecting surfactant content, cholesterol content and sonication time as independent variables and particle (vesicle) size, drug entrapment efficiency and % drug release as response variables for optimization studies. The timolol maleate niosomal (TMN) formulation was evaluated for particle size, pH and osmolality and was found to possess the desired properties. The developed TMN formulation was studied for % cumulative in-vitro drug release using bottle rotating apparatus (electrolab) and was found to be 79.98% over 8 hr period exhibiting sustained drug release profile. The ex-vivo trans-corneal drug permeation profile of developed TMN was studied using modified franz-diffusion cell apparatus (Permegear) and the % cumulative drug permeation across freshly excised goat cornea was found to be 65.90 % in 8 hrs duration, which was approximately 1.5 times higher than the conventional eye drop formulation. The developed TMN was also proved to be isotonic and non-irritant in HET-CAM ocular irritancy test. It was therefore, concluded from above studies, that the developed timolol maleate niosomal (TMN) formulation is better than conventional eye drops due to longer corneal retention, sustained drug release and better trans-corneal drug permeation and thereby higher ocular bioavailability, hence, would need less frequent administration.Â

Preparation and Evaluation of Chloramphenicol as Thermosensitive Ocular in- situ Gel

The purpose of this study was to develop poloxamer-based in-situ gel of chloramphenicol aiming to increase bioavailability and prolong corneal contact time, controlling drug release, and enhancing ocular bioavailability. The in-situ gel was prepared using different concentrations of poloxamer 407 combined with hydroxypropyl methyl cellulose (HPMC) or carbapol 940 to achieve gelation temperature about physiological temperature and improve rheological behavior and gelling properties of poloxamer gel. The prepared formulations were evaluated for their appearance, pH, and sol-gel transition temperature. The formulations F2, F3, and F5 have a gelation temperature within the accepted range 35-370C and were evaluated for their isotonicity, rheological studies, ocular irritation test, sterility and release studies. The selected formulations (F2,F3, and F5) isotonic, pseudoplastic, non irritant, pass sterility test, and the in vitro release demonstrated a diffusion-erosion controlled release of chloramphenicol over a period of 4 hr., 6 hr., and 6 hr. respectively.
 Key words: Chloramphenicol, in-situ gel, ocular dosage form, poloxamer.

Efficacy and Safety Evaluation of a Chlorine Dioxide Solution.

In this study, a chlorine dioxide solution (UC-1) composed of chlorine dioxide was produced using an electrolytic method and subsequently purified using a membrane. UC-1 was determined to contain 2000 ppm of gaseous chlorine dioxide in water. The efficacy and safety of UC-1 were evaluated. The antimicrobial activity was more than 98.2% reduction when UC-1 concentrations were 5 and 20 ppm for bacteria and fungi, respectively. The half maximal inhibitory concentrations (IC50) of H1N1, influenza virus B/TW/71718/04, and EV71 were 84.65 ± 0.64, 95.91 ± 11.61, and 46.39 ± 1.97 ppm, respectively. A 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test revealed that the cell viability of mouse lung fibroblast L929 cells was 93.7% at a 200 ppm UC-1 concentration that is over that anticipated in routine use. Moreover, 50 ppm UC-1 showed no significant symptoms in a rabbit ocular irritation test. In an inhalation toxicity test, treatment with 20 ppm UC-1 for 24 h showed no abnormality and no mortality in clinical symptoms and normal functioning of the lung and other organs. A ClO2 concentration of up to 40 ppm in drinking water did not show any toxicity in a subchronic oral toxicity test. Herein, UC-1 showed favorable disinfection activity and a higher safety profile tendency than in previous reports.

Risk Assessment of Persicaria nepalensis Extract by Skin Irritation, Ocular Irritation, and Maximization Tests for Delayed Hypersensitivity

Risk Assessment of Persicaria nepalensis Extract by Skin Irritation, Ocular Irritation, and Maximization Tests for Delayed Hypersensitivity

Design, formulation, and evaluation of in situ gelling ophthalmic drug delivery system comprising anionic and nonionic polymers

Background: The significant problem in the ocular drug delivery is the attainment of optimal drug concentration at the site of action. Development of therapeutic agents that require repeated long-term administration is a driver for the sustained release drug delivery systems, to result in less frequent dosing, and less invasive techniques. Therefore, to overcome the anatomical barriers and ocular bioavailability constrains, a novel drug delivery system in situ gels have been developed. Materials and Methods: The in situ gelling system comprises gellan gum, an anionic polymer responsible for the ionic gelation. Methylcellulose a nonionic polymer contributes for the viscosity and gels at the body temperature. The formulation was characterized for clarity, appearance, pH, gelation time, drug content estimation, rheological evaluation, effect of sterilization on the viscosity, in vitro diffusion study, isotonicity testing, and ocular irritation testing. Results and Discussion: The developed formulations exhibited sustained release of drug over 8 h thereby increasing residence time of the drug. Sterilization caused no effect on viscosity of the formulation. Optimized formulation was selected on the bases of ability to form instant gel and with increased viscosity of gel with a slow and prolonged in vitro drug release pattern. The optimized formulation was found to be nonirritating with no ocular damage or abnormal clinical signs to the cornea, iris, and conjunctiva. Conclusion: Hence, the developed ophthalmic in situ gel by virtue of its prolonged corneal residence time and sustained drug release could be considered a viable alternative to the conventional eye drops in achieving enhanced bioavailability.

Cross-linked chitosan-dextran sulphate vehicle system for controlled release of ciprofloxaxin drug: An ophthalmic application

The major challenge associated with conventional eye-drop is the rapid drug loss due to precorneal defence barrier. In this context, controlled-release system of ciprofloxacin-conjugated chitosan (CS)-Dextran sulphate (DS) nanoparticles (NPs) have been synthesized, to increase the bioavailability. The formulated drug delivery vehicle was evaluated for its therapeutic value in the simulated tear fluidat pH 7.4. Ophthalmic microbes were tested with this formulation, to confirm the drug efficacy; which showed conducive therapeutic values of both MIC and MBC. Ocular irritancy test was performed using HET-CAM test, which showed that the CS-DS system did not yield any vascular response, offering it to be a non-irritant to the ocular surface. The release studies showed monotonous controlled-release for duration of 21h. A fine cross-linking between CS and DS has been demonstrated to form CS-DS NPs and their interaction with drug has been evaluated using conventional characterization tools.

탁리소독음 피부외용제형의 급성경피독성시험, 피부자극시험 및 안점막자극시험

Objectives : Taglisodog-eum(TSE), a poly herbal formula, has been widely used to improve carbuncles by removing inflammation of the lymphatic channels in Traditional Korean Medicine. We previousely reported the action mechanism of TSE on experimental atopic dermatitis and the establishment of formulation for TSE ointment. In this study, we examined the toxicity test on skin and eye irritation by TSE ointment to prove the safety of Taglisodog-eum ointment in clinical use. Methods : Acute skin toxicity of the TSE ointment was evaluated in Sprague-Dawley(SD) rats. After dermal administration of TSE ointment(2,000mg/kg), body weight, mortality, and clinical signs of the rats were observed for 14days. Primary skin irritation and ocular irritation tests for TSE ointment were performed in male New Zealand White Rabbits. In dermal and ocular irritation test, body weight, mortality, clinical signs, Primary Irritation Index(P.I.I.), and The Index of Acute Ocular Irritaion(I.A.O.I.) of rabbit were observed after applying at abraded skin and eye balls with Taglisodog-eum ointment. Results : In the results of acute skin toxicity, no significant differences were found in body weight, the clinical sign and the mortality between control and TSE ointment treated group. In primary dermal irritation test, body weight, the clinical sign and the mortality were not significantly changed and Primary Irritation Index(P.I.I.) was 0.8, indicating TSE ointment as weak irritant material. In ocular irritation test, The Index of Acute Ocular Irritaion was 0.0, indicating TSE ointment as non-irritating to the eye of the rabbits. To evaluate toxicity of the TSE ointment in animal test, body weight, the clinical signs, the skin and eye irritation check were conducted; TSE ointment was considered to be weak dermal irritant in test animals. The no response of eye irritation test was observed in this experimental condition. Conclusions : According to the above toxicity test, We consider that this results is helpful for saying about the safety of TSE ointment in clinical use.

Enhancement of lomefloxacin Hcl ocular efficacy via niosomal encapsulation: in vitro characterization and in vivo evaluation

The aim of this study is to develop and evaluate niosomal dispersions loaded with the hydrophilic drug; lomefloxacin Hcl (LXN) for the management of ocular bacterial conjunctivitis. LXN-loaded niosomes were prepared by the thin film hydration method following a full factorial formulation design. Two independent variables were evaluated: the type of surfactant (X1) and the surfactant:cholesterol ratio (X2). The dependent variables comprised entrapment efficiency (EE%: Y1), particle size (PS: Y2) and zeta potential (ZP: Y3). The optimum formulation, N-LXN14 (Tw60: CH, 1:1), was spherical in shape and exhibited EE% of 68.41 ± 0.07, PS of 176.0 ± 0.98 and ZP of -40.70 ± 2.20 with a sustained release profile over 8 hours following the Higuchi model. N-LXN14 proved good physicochemical stability under refrigeration up to 3 months. Ocular irritancy test showed no signs of ocular toxicity, confirming the safety and suitability for ocular application. Microbiological evaluation of the antibacterial effect of N-LXN14 was conducted using the susceptibility test and through the induction of topical conjunctivitis by Staphylococcus aureus (S. aureus) followed by topical therapy. Susceptibility test manifested significantly higher percent inhibition of S. aureus and higher AUC0–12 h of N-LXN14 (604.59 ± 0.05) compared to the commercial product (126.25 ± 0.049). Both clinical observation and colony count of the infected eyes after eight days of treatment demonstrated significant improvement in therapeutic response. The infected eyes were completely healed with eradication of S. aureus. In conclusion, the results showed that LXN niosomal dispersions may serve as a promising superior ocular delivery system in the treatment of bacterial conjunctivitis.

A comparative study on the efficiency of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan surface modified nanostructured lipid carrier for ophthalmic delivery of curcumin

To develop a potential nanocarrier for the topical ocular administration of curcumin (CUR), a novel thiolated chitosan was synthesized by the covalent binding between N-acetyl-l-cysteine (NAC) and chitosan (CS) to surface modify the nanostructured lipid carrier loaded CUR (CUR-NLC). And the superiorities of the CS-NAC co polymer coated CUR-NLC over chitosan oligosaccharides (COS) or carboxymethyl chitosan (CMCS) modification were also verified in detail. As expected, the increment in particle size and the reversal of zeta potential occurred after surface decorating, and the most prominent electropositivity was obtained for the CS-NAC-CUR-NLC group. Additionally, the utilization of the CS-NAC coating demonstrated an effectively controlled release over 72h and attained a 6.4 and 18.8 fold increase in apparent permeability coefficients (Papp) compared with the CUR-NLC and the self-made eye drops, respectively. Meanwhile, the clearance rate of the NLC labeled with Rhodamine B was significantly delayed in the presence of CS-NAC. By contrast, CS-NAC-CUR-NLC was superior to the COS and CMCS coated ones in view of in vitro release, drug permeability and corneal retention. Moreover, the results of the in-vivo and in-vitro characteristics demonstrated that the promoting effect of CMCS coating was relatively weaker than COS coated ones. Ocular irritation test was executed on the CS-NAC-CUR-NLC, neither a sign of toxicity nor irritation to the external ocular tissues was observed. In conclusion, CS-NAC-CUR-NLC possesses a greater potential as an ocular drug-delivery system comparing with the COS-CUR-NLC and CMCS-CUR-NLC.

The potential use of novel chitosan-coated deformable liposomes in an ocular drug delivery system

In this study, novel chitosan-coated deformable liposomes (DL-CS) were proposed as an ocular drug delivery system to prolong pre-corneal retention, and improve transcorneal penetration and absorption. Flurbiprofen-loaded deformable liposomes (FP-DL) were prepared by a modified ethanol injection method and then coated with chitosan. Both DL and DL-CS exhibited a homogeneous particle size distribution, high encapsulation efficiency and good stability. After coating with 0.1% CS, the zeta potential was shifted from negative to positive. The apparent permeability coefficient of FP-DL-0.1% CS evaluated using isolated rabbit corneas was 1.29-, 1.95- and 4.59- fold greater than that of uncoated FP-DL, conventional liposomes and FP solution (P<0.01), respectively. The in vivo pre-corneal retention time and elimination dynamics were assessed using gamma scintigraphy technology. The area under the remaining activity-time of FP-DL-0.1% CS was prolonged 2.84- and 1.53-fold compared with that of the FP solution and FP-DL groups, respectively. Moreover, the ocular irritation test in vivo revealed that DL-0.1% CS produced no ocular damage or abnormal clinical signs. These results indicate that DL-CS appears to be a novel ophthalmic drug delivery strategy with the potential to overcome the limitations of conventional eye drops.