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

PURPOSE: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Middle ear application of a sodium hyaluronate gel loaded with neomycin in a Guinea pig model.

OBJECTIVE: Establishing methods for topical administration of drugs to the inner ear have great clinical relevance and potential even in a relatively short perspective. To evaluate the efficacy of sodium hyaluronate (HYA) as a vehicle for drugs that could be used for treatment of inner ear disorders. METHODS: The cochlear hair cell loss and round window membrane (RWM) morphology were investigated after topical application of neomycin and HYA into the middle ear. Sixty-five albino guinea pigs were used and divided into groups depending on the type of the treatment. Neomycin was chosen as tracer for drug release and pharmacodynamic effect. HYA loaded with 3 different concentrations of neomycin was injected to the middle ear cavity of guinea pigs. Phalloidin stained surface preparations of the organ of Corti were used to estimate hair cell loss induced by neomycin. The thickness of the midportion of the RWM was measured and compared with that of controls using light and electron microscopy. All animal procedures were pe rformed in accordance with the ethical standards of Karolinska Institutet. RESULT: Neomycin induced a considerable hair cell loss in guinea pigs receiving a middle ear injection of HYA loaded with the drug, demonstrating that neomycin was released from the gel and delivered to the inner ear. The resulting hair cell loss showed a clear dose-dependence. Only small differences in hair cell loss were noted between animals receiving neomycin solution and animals exposed to neomycin in HYA suggesting that the vehicle neither facilitated nor hindered drug transport between the middle ear cavity and the inner ear. One week after topical application, the thickness of the RWM had increased and was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal. CONCLUSION: HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced by hair cell loss.

Natural medicaments in endodontics -- a comparative study of the anti-inflammatory action.

The objective of this study was to evaluate the irritant potential of propolis, Casearia sylvestris, Otosporin and saline solution (control). Twenty-eight male Wistar rats were selected, anesthetized and four experimental sites were designed on their backs. Injections of 2% Evans blue were intravenously administered in the lateral caudal vein and 0.1 ml of the tested solutions was injected intradermally into the experimental sites. The animals were killed 1/2, 1, 3 and 6 hours after the injection of the solutions. Each piece of skin containing the lesion was immersed in formamide and incubated at 45 masculine C for 72 h. After filtration, optical density was measured in a spectrophotometer. Data were statistically analyzed by a 2-way non-parametric test. The highest values of extracted dye were observed at 3 hours characterizing a peak in the inflammatory process. Propolis was the least irritant solution. The natural medicaments tested in this study may be a valuable alternative for endodontic treatment.

Biopharmaceutical assessment of eye drops containing aloe (Aloe arborescens Mill.) and neomycin sulphate.

The subject of the studies was eye drops made of aloe, containing the group of aloe chemical substances of anti-inflammatory use and neomycin sulphate. The aim of the studies was to evaluate the permeability of biologically active aloe substances, determined as aloenin, through synthetic lipophilic and hydrophilic membranes in a standard perfusion apparatus and in vitro verification of the transport possibilities of these substances through the isolated cornea of pig's eye. The permeability process of biologically active aloe substances determined as aloenin, through synthetic lipophilic and hydrophilic membranes, was analyzed using the first-order kinetics. Estimated quotas of permeability rate constant show that the investigated chemical compounds of aloe, included in the eye drops, diffused through the applied membranes. The studies of permeability through isolated pig's cornea proved that biologically active aloe substances could not overcome this biological barrier. On the basis of biopharmaceutical studies it can be concluded that the eye drops containing aloe and neomycin sulphate, due to the lack of permeating abilities through the eye cornea, should be particularly useful in the treatment of inflammations and infections of external parts of the eye, such as conjuctiva, eyelid edges, lacrimal sac and cornea.

Myosin VIIA is required for aminoglycoside accumulation in cochlear hair cells.

Myosin VIIA is expressed by sensory hair cells and has a primary structure predicting a role in membrane trafficking and turnover, processes that may underlie the susceptibility of hair cells to aminoglycoside antibiotics. [3H]Gentamicin accumulation and the effects of aminoglycosides were therefore examined in cochlear cultures of mice with different missense mutations in the myosin VIIA gene, Myo7a, to see whether myosin VIIA plays a role in aminoglycoside ototoxicity. Hair cells from homozygous mutant Myo7ash1 mice, with a mutation in a nonconserved region of the myosin VIIA head, respond rapidly to aminoglycoside treatment and accumulate high levels of gentamicin. Hair cells from homozygous mutant Myo7a6J mice, with a mutation at a highly conserved residue close to the ATP binding site of the myosin VIIA head, do not accumulate [3H]gentamicin and are protected from aminoglycoside ototoxicity. Hair cells from heterozygotes of both alleles accumulate [3H]gentamicin and respond to aminoglycosides. Although aminoglycoside uptake is thought to be via apical surface-associated endocytosis, coated pit numbers on the apical membrane of heterozygous and homozygous Myo7a6J hair cells are similar. Pulse-chase experiments with cationic ferritin confirm that the apical endocytotic pathway is functional in homozygous Myo7a6J hair cells. Transduction currents can be recorded from both heterozygous and homozygous Myo7a6J hair cells, suggesting it is unlikely that the drug enters via diffusion through the mechanotransducer channel. The results show that myosin VIIA is required for aminoglycoside accumulation in hair cells. Myosin VIIA may transport a putative aminoglycoside receptor to the hair cell surface, indirectly translocate it to sites of membrane retrieval, or retain it in the endocytotic pathway.