Design and evaluation of proniosomes as a carrier for ocular delivery of lomefloxacin HCl

The current investigation aims to develop and evaluate novel ocular proniosomal gels of lomefloxacin HCl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Proniosomes were prepared using different types of nonionic surfactants solely and as mixtures with Span 60. The formed gels were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Only Span 60 was able to form stable LXN-proniosomal gel when used individually while the other surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span 60:Tween 60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80%), appropriate vesicle size (187?nm) as well as controlled drug release over 12?h. Differential scanning calorimetry confirmed the amorphous nature of LXN within the vesicles. Stability study did not show any significant changes in entrapment efficiency or vesicle size after storage for 3 months at 4?°C. P-LXN 7 was found to be safe and suitable for ocular delivery as proven by the irritancy test. The antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops.     

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 AUC_0–12?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.     

Inhibition of the ocular effects of sodium arachidonate by anti-inflammatory compounds

Topical administration of aqueous solutions of sodium arachidonate to the eyes of rabbits increases intraocular pressure, constricts the pupil and increases both the protein and prostaglandin content of aqueous humor. Arachidonic acid itself dissolved in arachis oil is less effective than sodium arachidonate, although addition of polysorbate mono-oleate greatly increases the effects produced by arachidonic acid. Pretreatment with topically applied non-steroidal anti-inflammatory agents prevents the ocular effects of sodium arachidonate, indomethacin being 2–4 times as potent as either indoxole or pirprofen. Dexamethasone was without effect in these experiments. The results suggested that non-steroidal anti-inflammatory agents deserve serious consideration for topical use in the treatment of ocular inflammation.     

Constitutive behavior of ocular tissues over a range of strain rates

The constitutive behavior of bovine scleral and corneal tissues is measured in tension and compression, at quasi-static and moderate strain rates. Experiments are conducted at strain rates up to about 50 strain per second by a pneumatic testing system developed to overcome noise and measurement difficulties associated with the time dependent test of low impedance materials. Results for the tissues at room and the natural bovine body temperatures are similar and indicate that ocular tissue exhibits nonlinear stiffening for increasing strain rates, a phenomena termed rate hardening. For example, at a tensile strain rate of 29/s, corneal tissue is found to develop 10 times the stress that it does quasi-statically at the same strain. Thus, conventional constitutive models will grossly underpredict stresses occurring in the corneo-scleral shell due to moderate dynamic events. This has implication to the accuracy of ocular injury models, the study of the stress field in the corneo-scleral shell for glaucoma research and tonometry measurements. The measured data at various strain rates is represented using the general framework of a constitutive model that has been used to represent biological tissue mechanical data. Here it is extended to represent the measured data of the ocular tissues over the range of tested strain rates. Its form allows for straightforward incorporation in various numerical codes. The experimental and analytical methods developed here are felt to be applicable to the test of human ocular tissue.     

The potential therapeutic of siRNA eye drops in ocular diseases

In recent years, researchers have expressed an ongoing interest in developing RNA interference (RNAi) technology for therapeutic gene suppression in various diseases. Preclinical studies in animal models and cultured cell studies indicated that RNAi technology was an effective experimental tool against a variety of ocular diseases, and some small interference RNA (siRNA) drugs have been entered into clinical trials in Stage I and Stage II. However, in these studies siRNAs were delivered into ocular tissues via either systemic or subconjunctival/intravitreous injection, which is invasive and harmful if repeated. Based on this evidence, we hypothesize that topical application of siRNA eye drops may be a safe and effective therapeutic option in ocular surface diseases with temporary changes of gene expression. Furthermore, siRNA eye drops targeting different genes may simultaneously treat several ocular surface diseases.     

Topical anesthetic creams

Topical anesthetic creams have positive applications in plastic surgery. For certain procedures, they can replace injected local anesthetics. By replacing injections with a topical cream, the negative effects associated with injections, such as pain, needle anxiety, and edema at the surgical site, are eliminated. A variety of U.S. Food and Drug Administration-approved topical anesthetic creams are available for use; however, much care must be taken when prescribing and administering these drugs, as anesthetic creams compounded in nonstandard doses can result in severe toxicity and death. When used appropriately, topical anesthetic creams can provide a safe and effective alternative to other forms of anesthesia. This article provides an overview of topical anesthetic creams, including availability, composition, safety, and efficacy.     

The need for anonymous genetic counseling and testing.

Concerns are mounting about the risks of genetic discrimination resulting from the release of predictive and presymptomatic genetic test results to employers, insurers, and others. The ability to keep this information confidential is questionable, particularly in view of the expansion of electronic medical databases. One solution is to afford individuals access to anonymous genetic counseling and testing. Probands would be identified only by a code that would not reveal personal information, and test results would be stored, retrieved, and released solely on the basis of this code. The experience with anonymous HIV testing, while not completely analogous, suggests that such an approach would be both practical and effective.     

Aqueous, oil, and ointment formulations of ketorolac: efficacy against prostaglandin E2-induced ocular inflammation and safety: A technical note

The efficacy of aqueous, oil, and ointment formulations of ketorolac against PGE₂-induced ocular inflammation in rabbits was evaluated, with monitoring of blinking rate and PMN and protein migration in tear fluid, following topical PGE₂ instillation. Ketorolac ophthalmic formulations protected the eye against inflammatory insult. Chronic topical administration of formulations for 10 days into rats' eyes did not lead to any appreciable gastrointestinal ulceration, which indicates that the formulations are safe for long-term use.     

Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment.

Molecules that selectively target and occlude new blood vessels would be useful for diagnosis and treatment of pathologies associated with angiogenesis. We show that a phage-derived human antibody fragment (L19) with high affinity for the ED-B domain of fibronectin, a marker of angiogenesis, selectively localizes to newly formed blood vessels in a rabbit model of ocular angiogenesis. The L19 antibody, chemically coupled to a photosensitizer and irradiated with red light, mediates complete and selective occlusion of ocular neovasculature and promotes apoptosis of the corresponding endothelial cells. These results demonstrate that new ocular blood vessels can be distinguished immunochemically from preexisting ones and suggest that the targeted delivery of photosensitizers may be effective in treating angiogenesis-related pathologies.     

A retrospective study of the incidence of adverse drug reactions from topical ocular medications

Objective: The purpose of this study was to gather general incidence data on adverse drug reaction rates from topical ocular medications. Study design: A retrospective study from January 1993 to March 1996 was conducted at the Columbus, Ohio Veterans Affairs Outpatient Clinic. Adverse drug reaction data was compiled for the topical ocular medications on formulary using monthly minutes from the Pharmacy and Therapeutics Committee. Data was analyzed using an incidence equation. Results: Of the seventeen reported adverse drug reactions, 76.5% were hypersensitivity reactions. No adverse reactions were reported for 1993. Dipivefrin 0.1% had the highest incidence rate of 1.1% in 1994 while apraclonidine 0.5% had the leading incidence rates of 6.6% and 5.6% for 1995 and 1996, respectively. Conclusion: This study found adverse drug reactions from topical ocular medications at this facility were mild and rare with an average incidence of 1.5%.     

15-Fluoro prostaglandin FP agonists: a new class of topical ocular hypotensives

A novel series of 15-fluoro prostaglandins with phenoxy termination of the omega-chain was synthesized and evaluated for binding and functional activation of the prostaglandin FP receptor in vitro and for side effect potential and topical ocular hypotensive efficacy in vivo. Compounds with the 15alpha-fluoride relative stereochemistry displayed EC50 values of 相似文献   

Pharmacotoxicological applications of an equivalent dermis: three measurements of cytotoxicity

The legal procedure for evaluating the toxicity of cosmetic, household, chemical and pharmaceutical products is still the irritancy Draize test on rabbits. Various irritation tests are currently being developed as alternatives toin vivo animal testing. Ourin vitro model system is composed of 24 equivalent dermis (ED) comprising a chitosan-cross-linked collagen-glycosaminoglycan matrix populated by foreskin fibroblasts. In evaluating this system for irritancy testing, three different measures of toxicity were used: MTT (dimethylthiazol diphenyltetrazolium bromide) reduction, and lactate dehydrogenase and interleukin-6 release. The experiments described herein represent a preliminary evaluation to determine the usefulness and predictive value of our 24 ED kit as an alternative method for the prediction of human dermal reaction, versus three chemical products: cadmium chloride, lauryl sulfate, and benzalkonium chloride. Preliminary results suggest that the ED may be a usefulin vitro model for the prediction of cutaneous and ocular toxicity and allow the development of a 24-skin-equivalent kit realized by seeding human normal keratinocytes onto the equivalent dermis.Abbreviations ED equivalent dermis - ECM extracellular matrix - FCM fibroblast culture medium - LDH lactate dehydrogenase - IL-6 interleukin-6 - MTT dimethylthiazol diphenyltetrazolium bromide     

Elevated TGFbeta signaling inhibits ocular vascular development

Alterations in the ocular vasculature are associated with retinal diseases such as retinopathy of prematurity and diabetic retinopathy. Vascular endothelial growth factor (VEGF) as a potent stimulator for normal and abnormal vascular growth has been extensively studied. However, little is known about secreted factors that negatively regulate vascular growth in ocular tissues. We now report that expression of a self-activating TGFbeta1 in the ocular lens of transgenic mice results in inhibition of retinal angiogenesis followed by retinal degeneration. Transgenic TGFbeta1 can rescue the hyperplasic hyaloid tissue and reverse the corneal deficiency in TGFbeta2-null embryos. These results demonstrate that TGFbeta signaling modulates development of ocular vasculature and cornea in a dosage-dependent manner and that TGFbeta1 can substitute for TGFbeta2 in ocular tissues.     

Liposomes are effective carriers for the ocular delivery of prophylactics

Liposomes containing acetylcholinesterase were prepared by the freeze-drying method. The multilamellar morphology of the vesicles was revealed by freeze-fracture electron microscopy and their size distribution was determined by quasi-elastic light scattering. The vesicle diameters were in the range of about 0.2-4.0 micron. The liposome preparations were tested for their ocular delivery of an entrapped cholinesterase enzyme in counteracting the miotic effect of diisopropylfluorophosphate (DFP), a prototype of a family of organophosphate poisons. The topical application of the enzyme-containing liposomes to the rabbit eye was found to confer a significant level of protection against DFP-induced miosis. In comparing the prophylactic effectiveness of different enzyme-bearing liposomes, positively charged vesicles were found to be more effective than either neutral or negatively charged vesicles. Although the precise protective mechanism is not clear, our in vitro studies indicate that DFP molecules freely associate with liposomes and tear fluid promotes the release of liposome-entrapped enzymes. Thus, it is conceivable that the enzyme-liposome complex may act somewhat like a sponge by sequestering DFP molecules which diffuse into the vesicle, and also by releasing the entrapped enzyme to combine with DFP, thereby neutralizing its in vivo toxic effect.     

体外皮肤刺激模型的生物标志研究进展

皮肤刺激试验是人类健康相关产品危险性评价的常见项目,传统皮肤刺激试验采用实验动物进行,成本高周期长,给动物造成一定程度的痛苦。近年来,多种替代动物试验的体外模型被开发和应用。体外试验主要通过定量检测细胞活性和代谢变化的生物标志物预测体内的效应,应用最广泛的生物标志物是细胞活性、炎性因子、胞质酶等,在生物技术的推动下,新的特异性标志物被开发和验证。     

Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits

Previously, we reported that a relatively selective adenosine A(2A) receptor agonist 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) elicited ocular hypotension in rabbits (Journal of Pharmacological Sciences 2005;97:501-509). In the present study, we investigated the effect of 2-CN-Ado on ocular blood flow in rabbit eyes. An intravitreal injection of 2-CN-Ado increased ocular blood flow, measured by a non-contact laser flowmeter. 2-CN-Ado-induced increase in ocular blood flow was accompanied with the retinal vasodilation. The increase in ocular blood flow was inhibited by an adenosine A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, but not by an adenosine A(2B) receptor antagonist alloxazine or an adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. The repetitive applications of topical 2-CN-Ado twice a day for 7 days produced a persistent increase in ocular blood flow with ocular hypotension. These results suggest that 2-CN-Ado increases the ocular blood flow mainly via adenosine A(2A) receptor, and that the topical application of 2-CN-Ado for several days not only increases the ocular blood flow but also prolong ocular hypotension, indicating that 2-CN-Ado may be a useful lead compound for the treatment of ischemic retinal diseases such as glaucoma.     

Management of recurrent apthous ulcer using Corticosteroids,Local anesthetics and nutritional supplements

Recurrent Aphthous ulcers are the most common oral lesions among dental patients. The ulcers, which usually occur on the nonkeratinized oral mucosa, can cause considerable pain and may interfere with eating, speaking, and swallowing. Therefore, it is of interest to report data on the management of recurrent aphthous ulcer using corticosteroids, local anesthetics and nutritional supplements. Case sheets of 76 patients who underwent treatment for recurrent aphthous ulcer between June 2019 and March 2020 at the Saveetha Dental College, India were used in this analysis. Data was analyzed using Chi square test at a P value < 0.05 that is statistically significant. Results show that topical anaesthetics in population (49%) were more effective that corticosteroids. Thus, topical anaesthetics are recommended for recurrent aphthous ulcer.     

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed.     

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed.     

Parental attitudes toward genetic testing for pediatric deafness

Recent molecular genetic advances have resulted in genetic testing becoming an option for deaf individuals and their families. However, there is little information about the interest in such testing. To investigate this issue, parents with normal hearing who have one or more deaf children were surveyed about their attitudes toward diagnostic, carrier, and prenatal genetic testing for deafness. This population was chosen because it represents the majority of individuals who are encountered in clinical practice, given that 90%-95% of deaf individuals are born to persons with normal hearing. Of 328 surveys distributed, 96 were completed and returned. Of the respondents, 96% recorded a positive attitude toward genetic testing for deafness, including prenatal testing, although none would use this information to terminate an affected pregnancy. All respondents had a poor understanding of genetics, with 98% both incorrectly estimating the recurrence risk of deafness and misunderstanding the concept of inheritance. Notably, these findings were similar in the group who had had genetic testing for their children and in the group who had not, suggesting either that the parents who received genetic testing did not receive genetic counseling or that the counseling was not effective. On the basis of these results, it was concluded that this population is interested in the use of genetic testing and that testing should not be done without first providing formal genetic counseling. Appropriate counseling can help parents to understand the risks, benefits, and limitations of genetic testing.