Preclinical Assessment of Nanostructured Liquid Crystalline Particles for the Management of Bacterial Keratitis: in-vivo and Pharmacokinetics Study

2021 ◽  
Author(s):  
Shreya Kaul ◽  
Upendra Nagaich ◽  
Navneet Verma
Keyword(s):  
Residence Time ◽  
Liquid Crystalline ◽  
Ex Vivo ◽  
Research Work ◽  
Poloxamer 407 ◽  
Pharmacokinetic Studies ◽  
Eye Drops ◽  
Statistical Experimental Design ◽  
Bacterial Keratitis

Abstract The research work was driven to develop novel nanostructured liquid crystalline particles of vancomycin for its improved pre-ocular residence time, ocular bio-availability, enhanced targeting, increased permeability, reduced dosing frequency, controlled drug release and reduced systemic side-effects. Formulation was developed by fragmenting cubic crystalline phase of glycerol monooleate, water and poloxamer 407. A four-factor, three-level Taguchi statistical experimental design was constructed to optimize the formulation. Formulations exhibited internal-cubic structure of the vesicles with particle size in the range of 51.11 ± 0.96 nm to 158.73 ± 0.46 nm and negative zeta potential. Ex-vivo transcorneal permeation studies demonstrated that the optimized cubosomes had 2.4-fold increase in apparent permeability co-efficient as compared to vancomycin solution. Whereas, in-vivo studies in rabbits demonstrated that the severity of keratitis was considerably lowered in day 3 with optimized cubosomes. Ocular pharmacokinetic studies evaluated level of drug in aqueous humor and results revealed that the time to peak concentration (Tmax) of vancomycin loaded cubosomal formulation was about 1.9-fold higher and mean residence time was 2.2-fold greater than vancomycin solution. Furthermore, histological examination revealed that the corneal layers displayed well-maintained morphology without any stromal swelling, consequently indicating safety of formulation. In conclusion, results manifested that the developed vancomycin loaded cubosomes could be a promising novel ocular carrier and an ideal substitute for conventional eye-drops for the management of bacterial-keratitis.

In vivo study of hypericin-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system in a mice model of vulvovaginal candidiasis

2021 ◽  
Author(s):  
Patricia Rocha de Araújo ◽  
Giovana Maria Fioramonti Calixto ◽  
Victor Hugo Sousa Araújo ◽  
Mariana Rillo Sato ◽  
Camila Fernanda Rodero ◽  
...  
Keyword(s):  
Liquid Crystalline ◽  
Ex Vivo ◽  
Vulvovaginal Candidiasis ◽  
Poloxamer 407 ◽  
Vaginal Fluid ◽  
Vaginal Mucosa ◽  
Ex Vivo Permeation ◽  
In Situ Gelling

Abstract The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.

scholarly journals Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2450
Author(s):  
Lucy Urwin ◽  
Katarzyna Okurowska ◽  
Grace Crowther ◽  
Sanhita Roy ◽  
Prashant Garg ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Bacterial Species ◽  
Resistance Mechanisms ◽  
Bacterial Keratitis ◽  
Corneal Surface ◽  
Corneal Infection ◽  
Infection Models

Bacterial keratitis is a corneal infection which may cause visual impairment or even loss of the infected eye. It remains a major cause of blindness in the developing world. Staphylococcus aureus and Pseudomonas aeruginosa are common causative agents and these bacterial species are known to colonise the corneal surface as biofilm populations. Biofilms are complex bacterial communities encased in an extracellular polymeric matrix and are notoriously difficult to eradicate once established. Biofilm bacteria exhibit different phenotypic characteristics from their planktonic counterparts, including an increased resistance to antibiotics and the host immune response. Therefore, understanding the role of biofilms will be essential in the development of new ophthalmic antimicrobials. A brief overview of biofilm-specific resistance mechanisms is provided, but this is a highly multifactorial and rapidly expanding field that warrants further research. Progression in this field is dependent on the development of suitable biofilm models that acknowledge the complexity of the ocular environment. Abiotic models of biofilm formation (where biofilms are studied on non-living surfaces) currently dominate the literature, but co-culture infection models are beginning to emerge. In vitro, ex vivo and in vivo corneal infection models have now been reported which use a variety of different experimental techniques and animal models. In this review, we will discuss existing corneal infection models and their application in the study of biofilms and host-pathogen interactions at the corneal surface.

scholarly journals Ex vivo and in vivo study of Kowa HA-2 applanation tonometer in the measurement of intraocular pressure in cats

2017 ◽  
Vol 38 (6) ◽  
pp. 3647
Author(s):  
Claudia Lizandra Ricci ◽  
Rogério Giuffrida ◽  
Glaucia Prada Kanashiro ◽  
Hilidia Stephania Rufino Belezzi ◽  
Carolina De Carvalho Bacarin ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ex Vivo ◽  
Clinical Signs ◽  
In Vivo Study ◽  
Eye Drops ◽  
Significant Difference ◽  
Applanation Tonometer ◽  
Ex Vivo Study ◽  
Healthy Eyes

The objective of this study was to evaluate the use of the Kowa HA-2 applanation tonometer in measuring intraocular pressure (IOP) in cats. Ten healthy eyes were used in an ex vivo study in which the calibration curve for manometry vs. tonometry was determined by artificially raising the IOP in 5 mmHg increments up to 60 mmHg (10-60 mmHg). Both eyes of 10 anesthetized cats were studiedin vivo to compare manometry vs. tonometry. In the ambulatory study, 78 healthy eyes, 7 eyes with glaucoma and 20 eyes with uveitis were evaluated by tonometry, which was performed with topical anesthesia and 1% fluorescein eye drops for the formation of fluorescein semicircles. The correlation coefficient (r²) between the manometer and the Kowa HA-2 tonometer was 0.993 and the linear regression equation was y = 0.0915x + 0.0878 in the ex-vivo study. In the in vivo study, the IOP values (mean±SD, in mmHg) in manometry were 15.6 ± 1.1(14.0 – 17.5) and in tonometry were 15.5 ± 1.2(13.5 – 17.2), with no significant difference (P > 0.05) between manometry and tonometry. In ambulatory study, using the Kowa HA-2 tonometer, the IOP values (mean±SD, in mmHg) were 15.0 ± 1.5 (11.8 – 18.3) for the healthy eyes, 38.4 ± 8.1(29.6 – 53.7) for glaucomatous eyes and 10.4 ± 2.0(5.3 – 12.2) for eyes with uveitis. There was a strong correlation and accuracy between the IOP values with the manometry and the Kowa HA-2 tonometer. In the ambulatorystudy the IOP values obtained with the tonometer were compatible for animals with healthy eyes and with clinical signs of glaucoma and uveitis. We conclude that the Kowa HA-2 tonometer can be used in the measurement of IOP in cats, since it is a practical and accurate method in this species.

scholarly journals Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1640
Author(s):  
Sreeja C. Nair ◽  
Kollencheri Puthenveettil Vinayan ◽  
Sabitha Mangalathillam
Keyword(s):  
Drug Release ◽  
Olfactory Epithelium ◽  
Drug Transport ◽  
Ex Vivo ◽  
Medical Attention ◽  
Pharmacokinetic Studies ◽  
Phenytoin Sodium ◽  
Drug Solution

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.

LIPID NANOPARTICLES FOR TRANSDERMAL DELIVERY OF CELECOXIB: AN IN VITRO AND IN VIVO INVESTIGATION

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (08) ◽  
pp. 38-48
Author(s):  
S. V Shinde ◽  
S Nikam ◽  
P Raut ◽  
M. K. Ghag ◽  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Ex Vivo ◽  
Research Work ◽  
Lipid Nanoparticles ◽  
Inflammatory Activity ◽  
Promising Alternative ◽  
Solid Lipid ◽  
Anti Inflammatory

In the present research work, celecoxib (CXB) loaded solid lipid nanoparticles (SLNs) were prepared using the probe sonication method, wherein Glyceryl monostearate and Tween 80 were used as solid lipid and surfactant, respectively. To obtain the statistically optimized batch, 32 factorial design was applied. The optimized batch was characterized physicochemically and evaluated through DSC, SEM and XRD studies. The mean particle size of the optimized batch was found to be 135.41± 0.24 nm with a mean % entrapment efficiency of 80 ± 1.69%. The optimized batch was further lyophilized and dispersed into 1% w/v Carbopol 934P to form a gel. Prepared gel was further evaluated for in vitro drug release, occlusivity, ex vivo permeability, local toxicity, in vivo anti-inflammatory activity and accelerated stability study. The study resulted in stable, safe and prolonged anti-inflammatory activity with quick onset of action. Hence, celecoxib loaded solid lipid nanoparticles can be considered as promising alternative to conventional topical systems.

scholarly journals Cyclosporine Lipid Nanocapsules as Thermoresponsive Gel for Dry Eye Management: Promising Corneal Mucoadhesion, Biodistribution and Preclinical Efficacy in Rabbits

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 360
Author(s):  
Lubna M. Eldesouky ◽  
Riham M. El-Moslemany ◽  
Alyaa A. Ramadan ◽  
Mahmoud H. Morsi ◽  
Nawal M. Khalafallah
Keyword(s):  
Dry Eye ◽  
Ex Vivo ◽  
Histopathological Examination ◽  
Entrapment Efficiency ◽  
Poloxamer 407 ◽  
Lipid Nanocapsules ◽  
Ocular Irritation ◽  
Schirmer Tear Test

An ophthalmic cyclosporine (CsA) formulation based on Lipid nanocapsules (LNC) was developed for dry eye management, aiming to provide targeting to ocular tissues with long-term drug levels and maximum tolerability. CsA-LNC were of small particle size (41.9 ± 4.0 nm), narrow size distribution (PdI ≤ 0.1), and high entrapment efficiency (above 98%). Chitosan (C) was added to impart positive charge. CsA-LNC were prepared as in-situ gels using poloxamer 407 (P). Ex vivo mucoadhesive strength was evaluated using bovine cornea, while in vivo corneal biodistribution (using fluorescent DiI), efficacy in dry eye using Schirmer tear test (STT), and ocular irritation using Draize test were studied in rabbits compared to marketed ophthalmic CsA nanoemulsion (CsA-NE) and CsA in castor oil. LNC incorporation in in-situ gels resulted in an increase in mucoadhesion, and stronger fluorescence in corneal layers seen by confocal microscopy, compared to the other tested formulations. Rate of recovery (days required to restore corneal baseline hydration level) assessed over 10 days, showed that CsA-LNC formulations produced complete recovery by day 7 comparable to CsA-NE. No Ocular irritation was observed by visual and histopathological examination. Based on data generated, CsA-LNC-CP in-situ gel proved to be a promising effective nonirritant CsA ophthalmic formulation for dry eye management.

scholarly journals Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies

Drug Delivery ◽  
2017 ◽  
Vol 24 (1) ◽  
pp. 692-700 ◽  
Author(s):  
Sara Nageeb El-Helaly ◽  
Ahmed Abd Elbary ◽  
Mohamed A. Kassem ◽  
Mohamed A. El-Nabarawi
Keyword(s):  
Ex Vivo ◽  
Brain Targeting ◽  
Pharmacokinetic Studies
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