Goat Cornea Research Articles

Efflux transporter inhibitory (EXTRIN) micelles for enhanced ocular drug delivery

Efflux transporters such as P-glycoprotein (P-gp) and Multidrug resistance proteins-2 (MRP-2) are often highly expressed on cornea and conjunctiva, significantly restricting the absorption of topically administered drugs into the eye. We hypothesized that nanocarrier with P-gp and MRP-2 inhibitory activity may enhance drug permeation across the cornea. Due to ease in development and scale-up, a lipidic nanocarrier was proposed and therefore lipids and surfactants were screened for P-gp and MRP-2 modulation using erythromycin (Ery), a known substrate for both P-gp and MRP-2 as model drug and freshly excised goat cornea as membrane. Out of the studied lipids/surfactants, Peceol and Pluronic F127 showed maximum inhibitory effects against P-gp and MRP-2 and were used to develop efflux transporter inhibitory micelles (EXTRIN-micelles). Dynamic laser scattering showed that EXTRIN-micelles were 348 ± 14.5 nm with PDI <0.09. Preclinical studies in rabbits demonstrated significantly higher (p < 0.05) corneal retention of EXTRIN-micelles compared to solution. Further, EXTRIN-micelles delivered significantly higher (p < 0.001) Ery concentrations to aqueous humor compared to solution. In conclusion, EXTRIN-micelles are potential carriers for enhanced ocular delivery of drugs.

Cubosomes; An Approach to Sustain and Improve the Ocular Delivery for Glaucoma Treatment: Box Benhken Optimization, Formulation, In Vitro Characterization and Ex Vivo Permeation Study

Introduction: In glaucoma, acetazolamide (ACZ) is used to lower intraocular pressure (IOP). Low aqueous solubility and decreased corneal permeation are two characteristics of ACZ. This research intends to enhance the ocular delivery of ACZ. Materials and Methods: Using a Box-Behnken design, cubosomes loaded with acetazolamide were made using the Melt dispersion emulsification and sonication method. The independent variables included Glyceryl monoolein (GMO), polyvinyl alcohol (PVA) and Poloxamer 407 (P407. The prepared formulations underwent evaluation for polydispersity index (PDI), particle size and entrapment efficiency. Thermal analysis, in vitro characterisation and permeation were among the additional tests performed on the developed formulation. Results: Optimized formulation showed PDI of 0.23 ± 0.03, mean particle size of 243 ± 4.2 nm, zeta potential of -26.1 ± 0.6 mV, entrapment efficiency of 73.99% and cubic structure under TEM. Drug penetration through goat cornea has increased, according to an ex vivo permeation study. The prepared cubosome safety, stability and ability to be delivered through the cornea were confirmed by the ocular irritation test. Conclusion: The optimized cubosomal formulation has the potential to improve glaucoma treatment and be regarded as promising for ocular delivery of ACZ.

Formulation and evaluation of Fluconazole Nanosuspensions: In vitro characterization and transcorneal permeability studies

The aim in this study was to develop and evaluate a nanofluconazole (FLZ) formulation with increased solubility and permeation rate using nanosuspensions. The FLZ nanosuspensions were stabilized using a variety of stabilizing agents and surfactants in various concentrations. The FLZ nanosuspension was characterized in vitro using particle size, zeta potential, X-ray powder diffraction (XRPD), and solubility. In addition, the ex vivo ocular permeation of FLZ through a goat cornea was analyzed. The results showed that the particle size of all nanosuspension formulations was in the nanometer range from 174.5 ± 1.9 to 720.2 ± 4.77 nm; that of the untreated drug was 18.34 μm. The zeta potential values were acceptable, which indicated suitable stability for formulations. The solubility of the nanosuspensions was up to 5.7-fold higher compared with that of the untreated drug. The results of the ex vivo ocular diffusion of the FLZ nanosuspensions showed the percentage of FLZ penetrating via the goat cornea increased after using Kollicoat to stabilize the nanosuspension formulation. Consequently, when using a nanosuspension formulation of Kollicoat, the antifungal activity of the drug strengthens.

Besifloxacin HCl Ophthalmic In situ Gel: Design, Optimization, In vitro and Ex vivo Investigation

The present work aimed to formulate and evaluate Besifloxacin Hydrochloride (HCl) ophthalmic in situ gel for conjunctivitis, based on temperature triggered gelation system to increase ocular residence time, bioavailability and patient compliance. Different formulations were prepared by using Poloxamer 407 and Poloxamer 188 as temperature sensitive as well as mucoadhesive polymers. Design expert software version 11 was used to optimized the formula. Optimized batch having Poloxamer 407 (24.80% w/v) and Poloxamer 188 (14.53% w/v) was evaluated for visual appearance, clarity, gelation temperature, gelling capacity, rheological property, ex vivo, in vitro release and accelerated stability studies. Histopathological study was carried out using Goat cornea and revealed no change in histopathology of the tissues. Formulation was found to be effective against the Escherichia coli and Staphylococcus aureus. Cumulative % drug release of Besifloxacin HCl ophthalmic in situ gel after 8 hours was found to be 96.47 %.

Formulation and Evaluation of Moxifloxacin Hydrochloride Loaded Cubosomal Gel for Ocular Delivery

This study aimed to develop and evaluate an ocular, prolonged-release cubogel formulation of moxifloxacin hydrochloride (MX) to treat conjunctivitis. Using glycerol monooleate and poloxamer 407 in varying concentrations, a cubosome containing the antibiotic MX was developed using a top-down approach. Further, by dispersing optimized cubosomes in a cold in-situ gelling system, MX cubogels were prepared. Following Higuchi's release kinetic model, formulations MA4, MA8, MA11, and MA14 released 95.84, 95.77, 97.45, and 97.68% of MX after 12 hours. The in-vitro corneal permeation study showed that the goat cornea absorbed 81% of MX cubogel than conventional formulations. From the results of antibacterial and histopathological studies, the selected formulations were safe for ocular administration. This study concluded that MX cubogel may be a suitable alternative to conventional eye drops due to its increased permeability and sustained release characteristics.&#x0D; Keywords: Conjunctivitis, Cubosome, Glycerol monooleate, Moxifloxacin hydrochloride Poloxamer 407

Gellan gum and sodium alginate in-situ gel of monocaprin for effective corneal permeation

Babies born to mothers suffering from gonorrhea may experience severe eye infections that might culminate in loss of vision. The eyes of the neonate can are infected with Neisseria gonorrhoeae, during birth. The primary goal of the study was to develop a stable aqueous ion-activated polymeric solution with clinically useful amounts of fatty acid-based monocaprin and a polymeric mixture of two commonly employed edible polysaccharide, sodium alginate and gellan gum. Monocaprin is an antibacterial agent against the treatment of gonococcal ophthalmia neonatorum, which was successfully formulated as an ion-activated in-situ gel-forming ophthalmic solution. The absence of drug-polymer interaction was confirmed from the FTIR study. The gelling capacity confirmed pH dependent (pH 7.2–7.4) sol-to-gel transition at 37°C±0.5°C. Formulation C4 was selected as the best formulation because it exhibited clear appearance, pH, good gelling capacity, optimum viscosity, 96.4% in-vitro drug release up to 11h. Formulation C4 also exhibited 96.6% drug release after 12h using goat cornea. The study results demonstrated remarkable enhancement in corneal permeation of in-situ gel in contrast to conventional eye drops. Sterility results showed no evidence of bacterial growth after 14 days in different media. The developed monocaprin incorporated sodium alginate and gellan gum based in situ gel formulation showed promising results with increased ocular residence and enhanced corneal permeability.

Chitosan-poly(lactide-co-glycolide)/poloxamer mixed micelles as a mucoadhesive thermo-responsive moxifloxacin eye drop to improve treatment efficacy in bacterial keratitis

A mucoadhesive self-assembling polymeric system was developed to carry moxifloxacin (M) for treating bacterial keratitis (BK). Chitosan-PLGA (C) conjugate was synthesized, and poloxamers (F68/127) were mixed in different proportions (1: 5/10) to prepare moxifloxacin (M)-encapsulated mixed micelles (M@CF68/127(5/10)Ms), including M@CF68(5)Ms, M@CF68(10)Ms, M@CF127(5)Ms, and M@CF127(10)Ms. The corneal penetration and mucoadhesiveness were determined biochemically, in vitro using human corneal epithelial (HCE) cells in monolayers and spheroids, ex vivo using goat cornea, and in vivo via live-animal imaging. The antibacterial efficacy was studied on planktonic biofilms of P. aeruginosa and S. aureus (in vitro) and Bk-induced mice (in vivo). Both M@CF68(10)Ms and M@CF127(10)Ms demonstrated high cellular uptake, corneal retention, muco-adhesiveness, and antibacterial effect, with M@CF127(10)Ms exhibiting superior therapeutic effects in P. aeruginosa and S. aureus-infected BK mouse model by reducing the corneal bacterial load and preventing corneal damage. Therefore, the newly developed nanomedicine is promising for clinical translation in treating BK.

Optimization and in vivo evaluation of triamcinolone acetonide loaded in situ gel prepared using reacted tamarind seed xyloglucan and kappa-carrageenan for ocular delivery

In the current work, triamcinolone acetonide (TAA) loaded dual responsive in situ gelling system was designed and optimized using reacted tamarind seed xyloglucan (RXG) (thermoresponsive) and kappa-Carrageenan (κ-CRG) (ion-sensitive) polymers. Tamarind seed xyloglucan (TSX) was subjected to purification followed by enzymatic treatment to produce RXG with ~40 % reduction in galactose content compared to TSX. RXG was characterized using size exclusion chromatography, Fourier transform infrared and proton nuclear magnetic resonance spectroscopy to confirm the ~40 % reduction in galactoside content compared to TSX. The proportions of RXG and κ-CRG in the in situ gels (TAA loaded RXG-κ-CRG) were optimized based on their rheological properties. The optimized in situ gel exhibited good flow properties at 25 °C, but transformed rapidly into a stronger gel in the presence of STF at 35 °C. The optimized formulation had strong mucoadhesion with good spreadability on the surface of excised goat cornea. The drug release followed zero-order kinetics from the optimized in situ gel. Ex vivo ocular toxicity studies indicate that the optimized formulation was well tolerated. The ocular pharmacokinetic studies in rabbits showed significantly higher and sustained vitreous humor exposure of TAA for optimized in situ gel compared to hydroxypropyl-β-cyclodextrin based aqueous suspension of TAA.

Mesoporous Silica Nanoparticles Coated with Carboxymethyl Chitosan for 5-Fluorouracil Ocular Delivery: Characterization, In Vitro and In Vivo Studies.

This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU). Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. The drug encapsulation and loading were determined by the indirect method using HPLC. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 ± 5.8%, and drug loading capacity of 5.2 ± 1.2%. NMR spectra confirmed the coating of AMSN with the CMC layer. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. AMSN-CMC-FU gel and AMSN-FU gel were "minimally irritating" to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.

Optimization of hyaluronan-enriched cubosomes for bromfenac delivery enhancing corneal permeation: characterization, ex vivo, and in vivo evaluation

To design and evaluate hyaluronan-based cubosomes loaded with bromfenac sodium (BS) for ocular application to enhance the corneal permeation and retention in pterygium and cataract treatment. BS-loaded cubosomes were prepared by the emulsification method, employing 23 full factorial design using Design-Expert® software. Glycerol monoolein (GMO) and poloxamer 407 (P407) as lipid phase and polyvinyl alcohol (PVA) as stabilizer were the used ingredients. The optimized formulation (OBC; containing GMO (7% w/w), P407 (0.7% w/w) and PVA (2.5% w/w)) was further evaluated. OBC had an entrapment efficiency of 61.66 ± 1.01%, a zeta potential of −30.80 ± 0.61 mV, a mean particle size of 149.30 ± 15.24 nm and a polydispersity index of 0.21 ± 0.02. Transmission electron microscopy confirmed its cubic shape and excellent dispersibility. OBC exhibited high stability and no ocular irritation that was ensured by histopathology. Ex vivo permeation study showed a significant increase in drug deposition and permeability parameters through goat cornea, besides, confocal laser microscopy established the superior permeation capability of OBC, as compared to drug solution. In vivo pharmacokinetics in aqueous humor indicated higher AUC0-tlast (18.88 µg.h/mL) and mean residence time (3.16 h) of OBC when compared to the marketed eye drops (7.93 µg.h/mL and 1.97 h, respectively). Accordingly, hyaluronan-enriched cubosomes can be regarded as a promising carrier for safe and effective topical ocular delivery.

Cationic Chitosan/Pectin Polyelectrolyte Nanocapsules of Moxifloxacin as Novel Topical Management System for Bacterial Keratitis

Purpose Moxifloxacin (MOX) is a fourth-generation fluoroquinolone and a broad spectrum antibiotic used in the management of bacterial keratitis (BK). This investigation aimed to formulate MOX-loaded chitosan/pectin cationic polyelectrolyte nanocapsules (CPNCs) for the effective topical treatment of BK. Methods Physicochemical properties like nanocapsule size, charge, drug entrapment efficiency (EE), viscosity, pH, and in-vitro release profile of CPNCs were evaluated. The in-vitro antibacterial activity of CPNCs and marketed formulations (MFs) was studied against Staphylococcus aureus. Ex-vivo corneal permeation studies of CPNCs were evaluated with the help of a modified diffusion apparatus, which was used with goat cornea. The pharmacodynamic study was performed with optimized CPNCs on a BK-induced rabbit eye model and compared with MF. Results The optimized nanocapsules appeared as positive charge (+19.91 ± 0.66) with a nano size (242.0 ± 0.30 nm) as calculated by the dynamic light scattering method. The in-vitro release profile of CPNCs exhibited sustained release properties. The ex-vivo permeation pattern also supported the improved drug permeation through the cornea from CPNCs as compared with MF. Draize irritation studies confirmed that the prepared formulation is compatible with the corneal tissue. The in-vivo study concluded that the antibacterial activity of CPNCs was improved when evaluated with MF. Conclusion The obtained results showed that CPNCs were the better choice for the management of BK therapy due to its capability to improve the corneal adhesion of CPNCs through direct interaction with the mucous membrane of the corneal tissue.

Design and optimization of gatifloxacin loaded polyvinyl alcohol nanofiber for the treatment of dry eye infection: In vitro and in vivo evaluation

According to a clinical report, nearly 50% of dry eye patients have an elevated risk of ocular infections and inflammations. Nanofiber could serve as a potential vehicle for treating anterior ocular disease because of its sterile nature, known solubility enhancing ability, capacity to carry multiple drugs, and controlled drug release capability, which can minimize overall dose and dosing frequency. As a result, the goal of this study was to assess the therapeutic potential of Gatifloxacin (GAF) loaded Polyvinyl alcohol (PVA) nanofiber for the treatment of dry eye syndrome with infection. Towards in vitro assessment, optimized nanofiber was characterized through surface imaging, swelling, release behavior, sterility, residual solvent, and degradation studies. Goat cornea was used to determine trans corneal penetrability. Therapeutic performance of the optimized nanofibers was assessed in a dry eye animal model. Results showed that applied potential of 12 kV, the flow rate of 3 μl/min, and plate to collector distance of 20 cm were the optimized electrospinning parameters for bead-free uniform fiber of around 200 nm. Longer precorneal contact time and biphasic release behavior, with an initial burst phase followed by a 7-h controlled release profile, are thought to reduce the need for frequent dosing to manage dry eye issues. Additionally, there was partial tear volume restitution and the tear ferns revival after 36h. Overall, the in-vitro and in-vivo results suggested that the developed product could be a viable alternative to manage dry eye infectious syndrome with less frequent dosing.

Gellan gum-based in situ gelling ophthalmic nanosuspension of Posaconazole.

The formulation and delivery of highly hydrophobic drugs in an optimized dosage form is challenging to formulation scientists. Posaconazole has shown promising action in case studies against fungal keratitis. Biological macromolecules like gellan gum would aid in enhancing the availability of such drugs by increasing the contact time of the formulation. Herein, we propose a transmucosal ocular delivery system of Posaconazole by developing a gellan gum–based in situ gelling nanosuspension. The HPLC method for Posaconazole was developed and validated as per ICH guidelines. The nanosuspension was prepared by microfluidization and optimized by Quality by Design. The gellan gum concentration selected was 0.4% w/v based on the viscosity and mucoadhesion measurements. A greater zone of inhibition of ~ 15 mm was observed for the prepared nanosuspension as compared to ~ 11 mm for the marketed itraconazole nanosuspension. A potential irritancy score of 0.85, considered to be non-irritant, was observed for the developed nanosuspension. Higher drug release of ~ 35% was noted for the nanosuspension compared to about ~ 10% for the coarse suspension. Ex vivo corneal retention studies on excised goat cornea demonstrated ~ 70% drug retention in the tissue.Graphical abstractGraphical abstract depicting the central hypothesis of the work. Supplementary informationThe online version contains supplementary material available at 10.1007/s13346-022-01155-0.

Statistical optimization of voriconazole nanoparticles loaded carboxymethyl chitosan-poloxamer based in situ gel for ocular delivery: In vitro, ex vivo, and toxicity assessment.

The research study reflects the development of novel voriconazole (VCZ) loaded nanoparticles (NPs) for prolonged delivery for the management of ocular diseases. The in situ ophthalmic gel was prepared by incorporating NPs into carboxymethyl chitosan (CMCh) and poloxamer. The central composite design was used to optimize the process for the preparation of nanoparticles by the o/w solvent evaporation method. The developed nanoparticles were evaluated for the encapsulation efficiency (89.6 ± 1.2%), particle size (219.3 ± 1.8nm), polydispersity index (PDI, 0.1), zeta potential (- 21.1 ± 1.12mV), saturation solubility, DSC study, and drug release. The etherification process grafts carboxyl surface functional groups, on chitosan, and was confirmed by FTIR and NMR studies. The developed CMCh-poloxamer based gelling system was found to be clear and transparent with gelation temperature varying from 33 to 40°C. The nanoparticle-loaded gel containing CMCh demonstrated enhanced antifungal activity against Candida albicans. The optimized batch containing CMCh showed improved mucoadhesion by 2.86-fold compared to VCZ nanosuspension. The drug release was prolonged up to 8h with an ex vivo study suggesting the enhanced permeation across goat cornea estimated via fluorescent microscope. The hen's egg chorioallantoic membrane study revealed that the formulation was non-irritant and tolerated by the chorioallantoic membrane. The present study concludes that the VCZ loaded nanoparticulate in situ ophthalmic gel using CMCh may act as a potential alternative for traditional eye drops.

Preparation of NLCs-Based Topical Erythromycin Gel: In Vitro Characterization and Antibacterial Assessment

In the present study, erythromycin (EM)-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification and ultra-sonication method. EM-NLCs were optimized by central composite design using the lipid (A), pluronic F127 (B) and sonication time (C) as independent variables. Their effects were evaluated on particle size (Y1) and entrapment efficiency (Y2). The optimized formulation (EM-NLCs-opt) showed a particle size of 169.6 ± 4.8 nm and entrapment efficiency of 81.7 ± 1.4%. EM-NLCs-opt further transformed into an in-situ gel system by using the carbopol 940 and chitosan blend as a gelling agent. The optimized EM-NLCs in situ gel (EM-NLCs-opt-IG4) showed quick gelation and were found to be stable for more than 24 h. EM-NLCs-opt-IG4 showed prolonged drug release compared to EM in situ gel. It also revealed significant high permeation (56.72%) and flux (1.51-fold) than EM in situ gel. The irritation and hydration study results depicted no damage to the goat cornea. HET-CAM results also confirmed its non-irritant potential (zero score). EM-NLCs-opt-IG4 was found to be isotonic and also showed significantly (p < 0.05) higher antimicrobial activity than EM in situ gel. The findings of the study concluded that NLCs laden in situ gel is an alternative delivery of erythromycin for the treatment of bacterial conjunctivitis.

Effect of nano-encapsulation using human serum albumin on anti-angiogenesis activity of bevacizumab to target corneal neovascularization: Development, optimization and in vitro assessment

Majorly in ocular neovascular diseases or corneal neovascularization, the up-regulation of vascular endothelial growth factor level has been observed. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits VEGF binding to its surface receptors. Intravitreal injections of anti-VEGF are the revolutionized treatment but, the weak point is the frequent injections to the eye site and which may lead to several complications. Hence, the current study aimed to assess the effect of nano-encapsulation using human serum albumin on the anti-angiogenesis activity of bevacizumab to target corneal neovascularization. Human serum albumin encapsulated bevacizumab nanoparticles were fabricated by the double emulsion solvent evaporation method. Screening and optimization of designed nanoparticles were carried out by using design of experiment (DoE) software. Optimized nanoparticles were characterized for various characteristics like FT-IR, size of the particles, polydispersity index, zeta potential, percentage of drug entrapment, SEM, TEM, XRD, DSC, drug release, drug release kinetics, drug permeation, ocular irritation (HET-CAM assay), histopathological study, and stability study. The compatibility between the components was confirmed by FT-IR and DSC studies. The average size of the nanoparticles was within the acceptable range. The entrapment efficiency was high and followed Korsmeyers-Peppas drug release kinetics. Transcorneal permeation of the drug was assessed by goat cornea. The SEM images showed nanoparticles were crystal type of structures with rough surfaces and spherical shapes of particles confirmed by TEM studies. HET-CAM assay disclosed that the formulation was safe to use and well-tolerated. Histopathological studies on goat cornea revealed no corneal tissue damage. Stability studies exhibited that the prepared nanoparticle formulation was stable in accelerated storage conditions. Thus, the currently designed novel formulation could increase the bioavailability and decrease the toxicity of bevacizumab during corneal neovascularization therapy. Overall, applications of this nano technique in drug delivery systems promise further opportunities for the future.

Formulation design and optimization of cationic-charged liposomes of brimonidine tartrate for effective ocular drug delivery by design of experiment (DoE) approach

Objective The present study was aimed to design and optimize brimonidine tartrate (BRT) loaded cationic-charged liposome formulation with enhanced trans-corneal drug permeation, prolonged corneal residence, and sustained drug release for effective ocular delivery. Methods Design of experiment (DoE) based formulation optimization was done by three-factor, three-level Box–Behnken design selecting lipid, cholesterol, and drug content as independent variables and particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and cumulative % drug release (CDR) as response variables. The optimized formulation consisting of 79.2 mM lipid, 36.2 mM cholesterol, and 15.8 mg/mL drug was prepared by thin film hydration-sonication method using EPCS:DOTAP (1:1) as lipid component and characterized for all desired critical quality attributes (CQAs), drug release kinetics, TEM, DSC, XRD analysis, ex vivo trans-corneal drug permeation, and physical stability studies. Results The optimized liposome formulation exhibited experimentally observed responses close to predicted values having 150.4 nm (PS), 0.203 (PDI), 30.62 mV (ZP), and 55.17% (EE). The observed CDR (%) was 36.15% at 1 h and 91.13% at 12 h exhibiting sustained drug release profile and followed Higuchi drug release kinetics. The TEM, DSC, and XRD studies revealed spherical, nanosized, small unilamellar vesicles effectively entrapping BRT in liposomes. The ex vivo permeation study across goat cornea recorded apparent permeability (P app) 1.011 ± 0.07 cm.min−1 and steady-state flux (J ss) 17.63 ± 1.22 µg.cm−2.min−1 showing >2-fold enhanced drug permeation as compared to BRT solution. Conclusion The developed liposomal formulation possessed all recommended CQAs in optimal range with enhanced trans-corneal drug permeation and remained physically stable in 3 months stability study.

Design and Evaluation of Natamycin Nanocrystals Loaded In Situ Gel for Ophthalmic Administration

Background: Natamycin belongs to a large group of naturally occurring polyene antifungal antibiotics derived from Streptomyces natalensis. Natamycin has a restrictive pharmaceutical role because of its extremely low aqueous solubility, which severely reduces the bioavailability of the drug. To improve the absorption of the drug, nanocrystals of natamycin were prepared and incorporated into in situ gel.&#x0D; Aim: To improve the solubility and absorption of natamycin nanocrystals by preparing nanocrystal in situ gel of natamycin for ophthalmic delivery&#x0D; Methodology: Natamycin nanocrystal was prepared using Sono-Precipitation method. Box-Behnken approach was employed to assess the influence of independent variables, namely concentration of stabilizer, sonication time and amplitude on particle size and zeta potential of the prepared nanocrystal.&#x0D; Optimized natamycin nanocrystal in situ gel formulations was characterized for various parameters like pH, viscosity, drug content, in vitro drug release and ex vivo permeation studies.&#x0D; Results: The optimized formulation of natamycin nanocrystal with a particle size of 293.9nm and zeta potential -14.6mV was incorporated into in situ gels. The pH triggered in situ gel was prepared using Carbopol and Hydroxypropyl methylcellulose (HPMC)., which showed clear preparation, pH of the formulation was closed to the pH of tear fluid, i.e., 7.4, viscosity showed pseudoplastic behaviour with immediate gelation remained for an extended period, and the drug content was around 99.70%. From the characterizations given above, PF-4 was optimized and evaluated for In vitro drug release showing slow and sustained release when compared to the marketed formulation and followed first-order kinetics with the diffusion-controlled mechanism. Ex vivo permeation through goat's cornea of PF-4 showed better permeation than marketed formulation. The stability studies of PF-4 showed that formulation was stable at the appropriate condition.&#x0D; Conclusion: Nanocrystals formulations of natamycin was successfully formulated and incorporated into in situ gels. Further in vivo studies need to be carried out for confirmation of pharmacological activity

Smartphone enabled miniaturized temperature controller platform to synthesize nio/cuo nanoparticles for electrochemical sensing and nanomicelles for ocular drug delivery applications.

Undoubtedly, various kinds of nanomaterials are of great significance due to their enormous applications in diverse areas. The structure and productivity of nanomaterials are heavily dependent on the process used for their synthesis. The synthesizing process plays a vital role in shaping nanomaterials effectively for better productivity. The conventional method requires expensive and massive thermal instruments, a huge volume of reagents. This paper aims to develop an Automatic Miniaturized Temperature Controller (AMTC) device for the synthesis of nickel oxide (NiO), copper oxide (CuO) nanoparticles, and nanomicelles. The device features a low-cost, miniaturized, easy-to-operate with plug-and-play power source, precise temperature control, and geotagged real-time data logging facility for the producing nanoparticles. With a temperature accuracy of ± 2°C, NiO and CuO nanoparticles, and nanomicelles are synthesized on AMTC device, and are subjected to different characterizations to analyze their morphological structure. The obtained mean size of NiO and CuO is 27.14nm and 85.13nm respectively. As a proof-of-principle, the synthesized NiO and CuO nanomaterials are validated for electrochemical sensing of dopamine, hydrazine, and uric acid. Furthermore, the study is conducted, wherein, Dexamethasone (Dex) loaded nanomicelles are developed using AMTC device and compared to the conventional thin-film hydration method. Subsequently, as a proof-of-application, the developed nanomicelles are evaluated for transcorneal penetration using exvivo goat cornea model. Ultimately, the proposed device can be utilized for performing a variety of controlled thermal reactions on a minuscule platform with an integrated and miniaturized approach for various applications.

Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation

The goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F 127), Kollicoat IR (KL), hydroxypropyl methylcellulose E3 (HPMC), xanthan gum (XG), polyvinyl pyrrolidone K30 (PVP), and sodium lauryl sulfate (SLS) upon the resulting nanoparticles was investigated. Additionally, the ex vivo release of the FLZ nanonized particles from ophthalmic gel bases was studied by using goat cornea, and the ocular pharmacokinetics of appropriate ophthalmic gel base containing optimized drug nanoparticle formula compared to the untreated drug were studied in rabbits. FLZ nanoparticles were successfully prepared with different concentrations of stabilizers. However, the effects of these stabilizers on nanoparticle size and zeta potential values varied according to the concentration and type of stabilizer used. Based on differential scanning calorimetry, the drug was in its amorphous state in the tested nanoparticle formulations. The results of ex vivo ocular diffusion of the FLZ nanoparticle gel formulations revealed an improvement compared to that with the FLZ untreated gel. Nanoparticle formula (F3) prepared by using 5% PL F127 showed small particle size (352 ± 6.1 nm) with zeta potential value of −18.3 mV with highest ex vivo release rate from goat cornea (100% after 6 h). Moreover, the AUC0-8h from ocular application of FLZ from sodium alginate gel containing nanoparticle formula F3 was 1.4-fold higher than that after its administration in the untreated formula. Based on our findings, the ophthalmic gel formulations containing FLZ nanoparticles enhanced drug corneal permeation and improved the ocular pharmacokinetic parameters.