Development of Timolol-Loaded Galactosylated Chitosan Nanoparticles and Evaluation of Their Potential for Ocular Drug Delivery

This study was conducted to develop timolol maleate (TM)-loaded galactosylated chitosan (GC) nanoparticles (NPs) (TM-GC-NPs) followed by optimization via a four-level and three-factor Box–Behnken statistical experimental design. The optimized nanoparticles showed a particle size of 213.3?±?6.83 nm with entrapment efficiency of 38.58?±?1.31% and drug loading of 17.72?±?0.28%. The NPs were characterized with respect to zeta potential, pH, surface morphology, and differential scanning calorimetry (DSC). The determination of the oil–water partition coefficient demonstrated that the TM-GC-NPs had a high liposolubility at pH 6 as compared to timolol-loaded chitosan nanoparticles (TM-CS-NPs) and commercial TM eye drops. The in vitro release study indicated that TM-GC-NPs had a sustained release effect compared with the commercial TM eye drops. Ocular tolerance was studied by the hen’s egg chorioallantoic membrane (HET-CAM) assay and the formulation was non-irritant and could be used for ophthalmic drug delivery. The in vitro transcorneal permeation study and confocal microscopy showed enhanced penetration, and retention in the cornea was achieved with TM-GC-NPs compared with the TM-CS-NPs and TM eye drops. Preocular retention study indicated that the retention of TM-GC-NPs was significantly longer than that of TM eye drops. The in vivo pharmacodynamic study suggested TM-GC-NPs had a better intraocular pressure (IOP) lowering efficacy and a prolonged working time compared to commercial TM eye drops (P?≤?0.05). The optimized TM-GC-NPs could be prepared successfully promising their use as an ocular delivery system.     

Ocular Cubosome Drug Delivery System for Timolol Maleate: Preparation,Characterization, Cytotoxicity, <Emphasis Type="Italic">Ex Vivo</Emphasis>, and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization. These constructed nanoparticles appeared spherical using transmission electron microscopy and had an average particle size of 142 nm, zeta potential of ?6.27 mV, and over 85% encapsulation efficiency. Moreover, using polarized light microscopy and small-angle X-ray scattering (SAXS), it was shown that the TM cubosomes have cubic liquid crystalline D-type (Pn3m) structure, which provides good physicochemical stability and high encapsulation efficiency. Ex vivo corneal permeability experiments showed that the total amount of TM cubosomes penetrated was higher than the commercially available eye drops. In addition, in vivo studies revealed that TM cubosomes reduced the IOP in rabbits from 27.8～39.7 to 21.4～32.6 mmHg after 1-week administration and had a longer retention time and better lower-IOP effect than the commercial TM eye drops. Furthermore, neither cytotoxicity nor histological impairment in the rabbit corneas was observed. This study suggests that cubosomes are capable of increasing the corneal permeability and bioavailability of TM and have great potential for ocular disease treatment.     

The role of nanotechnology in control of human diseases: perspectives in ocular surface diseases

Nanotechnology is the creation and use of materials and devices on the same scale as molecules and intracellular structures, typically less than 100?nm in size. It is an emerging science and has made its way into pharmaceuticals to significantly improve the delivery and efficacy of drugs in a number of therapeutic areas, due to development of various nanoparticle-based products. In recent years, there has been increasing evidence that nanotechnology can help to overcome many of the ocular diseases and hence researchers are keenly interested in this science. Nanomedicines offer promise as viable alternatives to conventional drops, gels or ointments to improve drug delivery to the eye. Because of their small size, they are well tolerated, thus preventing washout, increase bioavailability and also help in specific drug delivery. This review describes the application of nanotechnology in the control of human diseases with special emphasis on various eye and ocular surfaces diseases.     

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.     

Darunavir-Loaded Lipid Nanoparticles for Targeting to HIV Reservoirs

Darunavir has a low oral bioavailability (37%) due to its lipophilic nature, metabolism by cytochrome P450 enzymes and P-gp efflux. Lipid nanoparticles were prepared in order to overcome its low bioavailability and to increase the binding efficacy of delivery system to the lymphoid system. Darunavir-loaded lipid nanoparticles were prepared using high-pressure homogenization technique. Hydrogenated castor oil was used as lipid. Peptide, having affinity for CD4 receptors, was grafted onto the surface of nanoparticles. The nanoparticles were evaluated for various parameters. The nanoparticles showed size of less than 200 nm, zeta potential of ? 35.45 mV, and a high drug entrapment efficiency (90%). 73.12% peptide was found conjugated to nanoparticles as studied using standard BSA calibration plot. Permeability of nanoparticles in Caco-2 cells was increased by 4-fold in comparison to plain drug suspension. Confocal microscopic study revealed that the nanoparticles showed higher uptake in HIV host cells (Molt-4 cells were taken as model containing CD4 receptors) as compared to non-CD4 receptor bearing Caco-2 cells. In vivo pharmacokinetic in rats showed 569% relative increase in bioavailability of darunavir as compared to plain drug suspension. The biodistribution study revealed that peptide-grafted nanoparticles showed higher uptake in various organs (also in HIV reservoir organs namely the spleen and brain) except the liver compared to non-peptide-grafted nanoparticles. The prepared nanoparticles resulted in increased binding with the HIV host cells and thus could be promising carrier in active targeting of the drugs to the HIV reservoir.     

Biodegradable Ocular Inserts for Sustained Delivery of Brimonidine Tartarate: Preparation and <Emphasis Type="Italic">In Vitro</Emphasis>/<Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. Therefore, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglaucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K-90 (PVP K-90) as film-forming polymer blended with different viscosity grades of bioadhesive polymers namely hydroxypropyl methycellulose, carbopol, sodium alginate, and chitosan. The prepared ocular inserts were evaluated for various physicochemical parameters, swelling behavior, and in vitro release patterns. Sodium alginate-based ocular inserts revealed the most sustainment in drug release (99% at 6 h), so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The obtained in vitro release results for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP K-90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure (IOP) lowering effect when inserted in albino rabbits eyes showed superior sustainment effect compared with that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one-side-coated ocular insert showed more IOP lowering effect compared with that of its non-coated or dual-side-coated counterpart.     

<Emphasis Type="Italic">In vitro</Emphasis> and <Emphasis Type="Italic">In vivo</Emphasis> Studies on a Novel Bioadhesive Colloidal System: Cationic Liposomes of Ibuprofen

The objective of this study was to develop an ocular drug delivery system built on the cationic liposomes, a novel bioadhesive colloidal system, which could enhance the precorneal residence time, ocular permeation, and bioavailability of ibuprofen. The optimal formulation of cationic liposomes prepared by ethanol injection method was ultimately confirmed by an orthogonal L₉ (3³) test design. In addition, γ-scintigraphic technology and the microdialysis technique were utilized in the assessment of in vivo precorneal retention capability and ocular bioavailability individually. In the end, we acquired the optimal formulation of ibuprofen cationic liposomes (Ibu-CL) by orthogonal test design, and the particle size and entrapment efficiency (EE%) were 121.0 ± 3.5 nm and 72.9 ± 3.4%, respectively. In comparison to ibuprofen eye drops (Ibu-ED), Ibu-CL could significantly prolong the T _max to 100 min and the AUC to 1.53-folds, which indicated that the Ibu-CL could improve the precorneal retention time and bioavailability of ibuprofen. Consequently, these outcomes designated that the ibuprofen cationic liposomes we researched probably are a promising application in ocular drug delivery system.     

Design and development of ethosomal transdermal drug delivery system of valsartan with preclinical assessment in Wistar albino rats

Abstract

Valsartan (VLT) is a highly selective and orally active antihypertensive drug. However, its oral administration is associated with drawbacks like low bioavailability. The objective of this study was to design and develop a transdermal delivery system for VLT using ethosomal carriers to investigate their enhanced transdermal delivery potential. VLT ethosomes were prepared by cold method. VLT ethosomes were characterized by scanning electron microscopy. The prepared ethanolic liposomes were characterized to be spherical having low polydispersity of nano-size range with good entrapment efficiency. ETC5 ethosomal suspension with 4% of phospholipon 90H and 40% of ethanol was found to have highest entrapment efficiency, i.e. 80.230?±?0.8748%. The permeation study of ethosomes was evaluated by ex vivo diffusion study through rat abdominal skin using Franz’s diffusion cells and ETC5 ethosomal suspension was found to have highest permeation with flux of 92.819?±?1.539?µg/cm²/h, when compared to the permeation profiles of drug solutions either in water or in a water–ethanol mixture. Transdermal application of ethosomal VLT on Wistar rats showed better and prolonged antihypertensive activity in comparison to orally administered VLT suspension by virtue of transdermal permeation through Wistar rat skin. Histopathological study of skin applied with ETC5 showed intercellular permeation across skin by dissolving intercellular lipids in epidermis without causing any rigorous changes in the skin cellular structure. In conclusion, ethosomes enabled the transdermal permeation of VLT, which amply proves its superiority over oral administration for antihypertensive treatment.     

Nanomaterials for ocular drug delivery

Efficient drug delivery to the eye remains a challenging task for pharmaceutical scientists. Due to the various anatomical barriers and the clearance mechanisms prevailing in the eye, conventional drug delivery systems, such as eye drop solutions, suffer from low bioavailability. More invasive methods, such as intravitreal injections and implants, cause adverse effects in the eye. Recently, an increasing number of scientists have turned to nanomaterial-based drug delivery systems to address the challenges faced by conventional methods. This paper highlights recent applications of various nanomaterials, such as polymeric micelles, hydrogels, liposomes, niosomes, dendrimers, and cyclodextrins as ocular drug delivery systems to enhance the bioavailability of ocular therapeutic agents.     

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09?±?6.21%, 55.74?±?6.26%, and 62.54?±?3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.     

Enhancement of oral bioavailability of pentoxifylline by solid lipid nanoparticles

Pentoxifylline (PTX) is a highly water-soluble, hemorheologic drug that undergoes first-pass effect with 20% bioavailability. The solid lipid nanoparticles (SLNs) of PTX were prepared to enhance its oral bioavailability by homogenization, followed by the sonification method. Seven different variables, each at two levels, were studied: lipid type, surfactant type and concentration, speed of homogenizer, acetone:dichloromethane (DCM) ratio, lecithin:lipid ratio, and sonication time. The mean particle size and size distribution, drug entrapment efficiency (EE%), zeta potential, and drug release of the SLNs were investigated. A pharmacokinetic study was conducted in male Wistar rats after oral administration of 10?mg kg^?1 PTX in the form of free drug or SLNs. The z-average particle size, zeta potential, and EE% of the SLNs were at least 250?nm, ?30.2 mV, and 70%, respectively. Among the studied factors, the lipid type, surfactant type, and percentage had a significant effect on the particle size. Zeta potential was more affected by lipid type, acetone:DCM ratio, and sonication time. Speed of homogenizer and acetone:DCM ratio had a significant effect on the EE%. The optimized SLN was prepared by 80?mg of cetyl alcohol, 10?mg of lecithin, acetone:DCM ratio (1:2), 30-second sonication, 3% Tween 20, and a mixing rate of 800?rpm. In vitro drug release lasted for about 5 hours. It was found that the relative bioavailability of PTX in SLNs was significantly increased, compared to that of the PTX solution. SLNs offer a promising approach to improve the oral bioavailability of PTX that is affected by a high first-pass effect.     

Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride

Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.     

Ocular amphotericin B delivery by chitosan-modified nanostructured lipid carriers for fungal keratitis-targeted therapy

Abstract

Context: Fungal keratitis, a corneal fungal infection of the eye caused mainly by Candida species, has become the leading cause of blindness resulting from corneal disease in China. Present limitations in the management of ophthalmic fungal infections include the inability to provide long-term extraocular drug delivery without compromising intraocular structures and/or systemic drug exposure.

Objective: The aim of this study was to construct amphotericin B (AmB) loaded, chitosan-modified, nanostructured lipid carriers (AmB-CH-NLC) for prolonged ocular application and for the improvement of the targeted delivery of AmB to the ocular mucosa.

Materials and methods: The AmB-CH-NLC was produced by the method of emulsion evaporation-solidification at low temperature. The particle size, zeta potential, and encapsulation efficiency, drug-release behavior, and corneal penetration ability were performed in vitro and in vivo.

Results and discussion: The prepared AmB-CH-NLC nanoparticles exhibited a measured size of 185.4?nm, a zeta potential of 27.1?mV, and an entrapment efficiency of 90.9%. Sustained drug release behavior was observed in vitro. The in vivo ocular pharmacokinetic study indicated improved bioavailability of AmB-CH-NLC. The corneal penetration study showed that the AmB-CH-NLC could successfully penetrate into the cornea with no obvious irritation to the rabbits’ eyes.

Conclusion: The results support that this novel nanomedicine could be a promising system for effective ocular delivery of amphotericin B for fungal keratitis-targeted therapy.     

Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box–Behnken design

The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box–Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100?mg GMS, 150?mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8?±?4.9?nm. The polydispersity index of particle size was 0.239?±?0.01 and the zeta potential was 32.7?±?2.6?mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4?°C).     

N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin

The aims of this study were to design the formulation of curcumin (CUR) liposomes coated with N-trimethyl chitosan chloride (TMC) and to evaluate in vitro release characteristics and in vivo pharmacokinetics and bioavailability of TMC-coated CUR liposomes in rats. The structure of synthesized TMC was examined by infrared spectroscopy, with the presence of trimethyl groups, and by proton nuclear magnetic resonance spectroscopy, indicating the high degree of substitution quaternization (65.6%). Liposomes, composed of soybean phosphotidylcholine, cholestrol, and D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared by a thin-film dispersion method. Characteristics of the CUR liposomes, including entrapment efficiency (86.67%), drug-loading efficiency (2.33%), morphology, particle size (221.4?nm for uncoated liposomes and 657.7?nm for TMC-coated liposomes), and zeta potential (-9.63 mV for uncoated liposomes and +15.64 mV for TMC-coated liposomes) were investigated. Uncoated CUR liposomes and TMC-coated CUR liposomes showed a similar in vitro release profile. Nearly 50% of CUR was released from liposomes, whereas 80% of CUR was released from CUR propylene glycol solution. CUR incorporated into TMC-coated liposomes exhibited different pharmacokinetic parameters and enhanced bioavailability (C(max)?=?46.13 μg/L, t(1/2)?=?12.05 hours, AUC?=?416.58 μg/L·h), compared with CUR encapsulated by uncoated liposomes (C(max)?=?32.12 μg/L, t(1/2)?=?9.79 hours, AUC?=?263.77 μg/L·h) and CUR suspension (C(max)?=?35.46 μg/L, t(1/2)?=?3.85 hours, AUC?=?244.77 μg/L·h). In conclusion, oral delivery of coated CUR liposomes is a promising strategy for poorly water-soluble CUR.     

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.     

Enhanced Solubility and Bioavailability of Naringenin via Liposomal Nanoformulation: Preparation and <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluations

This study was aimed at preparing orally administered naringenin-loaded liposome for pharmacokinetic and tissue distribution studies in animal models. The liposomal system, consisting of phospholipid, cholesterol, sodium cholate, and isopropyl myristate, was prepared using the thin-film hydration method. Physicochemical characterization of naringenin-loaded liposome such as particle size, zeta potential, and encapsulation efficiency produced 70.53?±?1.71 nm, ?37.4?±?7.3 mV, and 72.2?±?0.8%, respectively. The in vitro release profile of naringenin from the formulation in three different media (HCl solution, pH 1.2; acetate buffer solution, pH 4.5; phosphate buffer solution, pH 6.8) was significantly higher than the free drug. The in vivo studies also revealed an increase in AUC of the naringenin-loaded liposome from 16648.48 to 223754.0 ng·mL^?1 h as compared with the free naringenin. Thus, approximately 13.44-fold increase in relative bioavailability was observed in mice after oral administration. The tissue distribution further showed that the formulation was very predominant in the liver. These findings therefore indicated that the liposomal formulation significantly improved the solubility and oral bioavailability of naringenin, thus leading to wider clinical applications.     

Serum eye drops,amniotic membrane and limbal epithelial stem cells—tools in the treatment of ocular surface disease

The advent of serum eye drops, amniotic membrane and limbal stem cell grafts, have transformed the treatment of diseases which result in ocular surface failure. This article provides an overview of ocular surface anatomy and failure, and how the use of serum eye drops, amniotic membrane and limbal epithelial stem cell transplantation has influenced ophthalmological practice both historically and in recent years. This review focuses on the rationale for the use of these emerging tools, how they are prepared, clinical applications, limitations, and speculates on future directions.     

Nanovesicular Formulation of Brimonidine Tartrate for the Management of Glaucoma: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

In this study, nanovesicles were developed for brimonidine tartrate by film hydration technique and dispersed in viscous carbopol solution for ocular delivery. Scanning electron microscopy revealed spherical shape of the vesicles. As high as 32.27% drug entrapment efficiency was achieved depending upon the surfactant/cholesterol molar ratio (7:4 to 7:8). The vesicles were in the size range of 298.0–587.9 nm. Release study showed a biphasic drug-release pattern for the lyophilized vesicular formulation in buffered saline solution, i.e., initial burst release followed by gradual release over the period of 8 h. On contrary, the isolated vesicles reduced the burst effect in 3 h by two to three times and the drug release was comparatively slower at the intermediate ratio in both cases. With variation in cholesterol content, the drug release followed either first order or Higuchi’s kinetics. Physically the lyophilized vesicular formulations were more stable at refrigerated temperature. DSC and X-RD analyses indicated loss of drug crystallinity in the vesicles. FTIR spectroscopy did not reveal any interaction between drug and excipients. The lyophilized formulation showed better ocular hypotensive activity than marketed drops on albino rabbits and in vivo efficacy was sustained up to 7.5 h. Furthermore, the formulation was found to be non-irritant to the rabbit eye. Hence, the lyophilized vesicles, when dispersed in viscous carbopol solution, had the potential in reducing dosing frequency and could improve patient compliance.     

珍珠明目液消炎作用观察

目的观察珍珠明目液对眼结膜刺激性及其对实验性兔眼部炎症的影响.方法给兔眼眶内滴入珍珠明目液(每次0.1ml/眼,1天3次,连续7天),观察给药7天后角膜、虹膜及结膜的反应;用30%巴豆油造成兔眼结膜炎,致炎前及致炎后局部应用珍珠明目液滴眼(0.1ml/眼),并设醋酸可的松眼药水治疗组和生理盐水对照组.于致炎后2、4、12、24、36、48及72h,根据结膜炎充血、水肿及分泌物轻重程度进行评分.结果珍珠明目液对兔眼角膜、虹膜及结膜未见明显异常反应.珍珠明目液治疗30%巴豆油所致兔眼炎症评分值显著低于相应生理盐水组(P＜0.01),与醋酸可的松治疗组比较无显著性差异.结论珍珠明目液无眼刺激性,对巴豆油致兔眼结膜炎具有较好的消炎作用.