New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.

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Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

Current Molecular Pharmacology ◽

10.2174/1874467214666210120160016 ◽

2021 ◽

Vol 14 ◽

Author(s):

Sarbjot Kaur ◽

Ujjwal Nautiyal ◽

Pooja A. Chawla ◽

Viney Chawla

Keyword(s):

Drug Delivery ◽

Ex Vivo ◽

In Vitro Release ◽

Nanostructured Lipid Carriers ◽

Polydispersity Index ◽

Poloxamer 407 ◽

Ex Vivo Permeation ◽

Permeation Studies ◽

Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

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Emulgels Containing Carbopol 934P and Different Vegetable Oils for Topical Propolis Delivery: Bioadhesion, Drug Release Profile, and Ex Vivo Skin Permeation Studies

AAPS PharmSciTech ◽

10.1208/s12249-020-01748-3 ◽

2020 ◽

Vol 21 (6) ◽

Author(s):

Rafaela Said dos Santos ◽

Camila Félix Vecchi ◽

Hélen Cássia Rosseto ◽

Jéssica Bassi da Silva ◽

Maria Eduarda Lima Dano ◽

...

Keyword(s):

Drug Release ◽

Vegetable Oils ◽

Ex Vivo ◽

Skin Permeation ◽

Release Profile ◽

Drug Release Profile ◽

Permeation Studies ◽

Carbopol 934P

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

Medical Mycology ◽

10.1093/mmy/myab006 ◽

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.

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Development and Evaluation of Particulate Microcarriers of Adapalene as a Topical Delivery System

Drug Delivery Letters ◽

10.2174/2210303109666190227163606 ◽

2019 ◽

Vol 9 (3) ◽

pp. 222-233

Author(s):

Divya D. Jain ◽

Namita D. Desai

Keyword(s):

Patient Compliance ◽

Targeted Delivery ◽

Ex Vivo ◽

Acne Vulgaris ◽

Drug Loading ◽

Topical Therapy ◽

Skin Irritation ◽

Topical Delivery ◽

Diffusion Method ◽

Topical Gel

Background: Adapalene is a promising third generation retinoid used in the topical treatment of acne vulgaris. However, the major drawback associated with conventional topical therapy of Adapalene is the ‘retinoid reaction’ which is dose-dependent and characterized by erythema, scaling and burning sensation at the application sites. Microparticulate drug delivery can play a major role in reducing side effects and providing better patient compliance due to targeted delivery. Methods: Adapalene microparticles were prepared using quasi emulsion solvent diffusion method. The effects of formulation variables including polymer ratios, amounts of emulsifier, drug loading and process variables such as stirring time and speed on the physical characteristics of microparticles were investigated. The developed microparticles were characterized by DSC and SEM. Adapalene microparticles were incorporated into Carbopol 971 NF gel for ease of topical delivery. Results: Adapalene microparticulate topical gel showed sustained drug release over 8 hours in in vitro studies. The amount of drug retained in the rat skin during ex vivo studies was higher in the microparticulate topical gel (227.43 ± 0.83 µg/cm2) as compared to the marketed formulation (81.4 ± 1.11 µg/cm2) after 8 hours indicating localized and sustained drug action that can be useful in treating acne vulgaris. The safety of optimized Adapalene gel determined by skin irritation studies performed on Sprague Dawley rats showed no irritation potential. Conclusion: Microparticles can provide promising carrier systems to deliver Adapalene, improving patient compliance due to enhanced skin deposition, localized and sustained action with reduced associated irritant effects.

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Development, Pre-clinical Investigation and Histopathological Evaluation of Metronidazole Loaded Topical Formulation for Treatment of Skin Inflammatory disorders

Drug Delivery Letters ◽

10.2174/2210303110999200821123047 ◽

2020 ◽

Vol 10 ◽

Author(s):

Divya Thakur ◽

Gurpreet Kaur ◽

Sheetu Wadhwa ◽

Ashana Puri

Keyword(s):

Ex Vivo ◽

Clinical Investigation ◽

In Vivo Studies ◽

Tween 20 ◽

Inflammatory Disorders ◽

Rat Paw Edema ◽

Ex Vivo Permeation ◽

Permeation Studies ◽

Anti Inflammatory

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at target site, which requires frequent administration and poor patient compliance. Objective: The aim of current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed average diameter and polydispersity index of selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion i.e. 21.90 ± 1.92 μg/cm2 which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm2 (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests efficacy of the developed MTZ loaded microemulsion in treatment of chronic skin inflammatory disorders.

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Polishing the Therapy of Onychomycosis Induced by Candida spp.: Amphotericin B–Loaded Nail Lacquer

Pharmaceutics ◽

10.3390/pharmaceutics13060784 ◽

2021 ◽

Vol 13 (6) ◽

pp. 784

Author(s):

Aleph M. S. Souza ◽

Renato C. A. Ribeiro ◽

Gleyse K. L. O. Pinheiro ◽

Francisco I. Pinheiro ◽

Wógenes N. Oliveira ◽

...

Keyword(s):

Amphotericin B ◽

Ex Vivo ◽

Drug Loading ◽

Drug Bioavailability ◽

Candida Spp ◽

Drying Time ◽

Analytical Method Validation ◽

Nail Lacquer ◽

In Vitro Adhesion

Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅ 7 days (≅ 90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%w/w, water-resistance of approximately 2%w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis.

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Design of Mucoadhesive Strips for Buccal Fast Release of Tramadol

Pharmaceutics ◽

10.3390/pharmaceutics13081187 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1187

Author(s):

Nayla Francine Garcia Pastório ◽

Camila Felix Vecchi ◽

Rafaela Said dos Santos ◽

Marcos Luciano Bruschi

Keyword(s):

Ex Vivo ◽

Polymer Concentration ◽

Peroral Administration ◽

Patient Acceptance ◽

Poly Vinyl Alcohol ◽

Synthetic Analogue ◽

Drug Release Profile ◽

Opioid Agonist ◽

In Vivo Evaluation ◽

Tramadol Hydrochloride

Tramadol hydrochloride is a synthetic analogue of codeine and shows activity on the central nervous system as an opioid agonist and inhibitor of serotonin and norepinephrine reuptake. It has been used for controlling moderate to severe pain. Mucoadhesive fast-dissolving films can present greater drug availability and patient acceptance when compared to the systems of peroral administration. The films were prepared using the solvent casting method with ethylcellulose, polyvinylpyrrolidone and poly(vinyl alcohol). The effect of each polymer concentration was investigated using a 2³ factorial design with repetition at the central point. The formulations were subjected to physicochemical, mechanical, ex vivo mucoadhesive and in vitro drug release profile analysis. These properties were dependent on the polymeric composition (independent factors) of each system. The optimized formulations showed good macroscopic characteristics, improved resistance to bending, rigidity, rapid swelling up to 60 s, improved mechanical and mucoadhesive characteristics, and also fast dissolving and tramadol release. The optimized formulations constitute platforms and strategies to improve the therapy of tramadol with regard to availability at the site of application, considering the necessity of rapid pain relief, and show potential for in vivo evaluation.

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Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model

Mycopathologia ◽

10.1007/s11046-021-00530-8 ◽

2021 ◽

Vol 186 (2) ◽

pp. 177-188

Author(s):

Ying Wu ◽

Lisha Jiang ◽

Lingling Zhang ◽

Xia Liu ◽

Lina Yan ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Basal Layer ◽

Vulvovaginal Candidiasis ◽

Control Group ◽

Therapeutic Effects ◽

Blank Control Group ◽

Candida Spp ◽

Expression Levels ◽

Gene And Protein Expression

AbstractVulvovaginal candidiasis (VVC) caused by Candida spp. affects 70–75% of women at least once during their lives. We aim to elucidate the potential mechanism of VVC and investigate the therapeutic effects of long noncoding RNA 9708-1. Female BALB/c mice were randomized to four treatment groups, including the blank control group, VVC control group, vehicle control group and lncRNA 9708-1-overexpressed group. Mice were euthanized on Day 4, Day 7 and Day 14 after treatment. Colony-forming unit (CFU) was measured, and the inflammation was detected by hematoxylin and eosin (H&E). Gene and protein expression levels of lncRNA 9708-1 and FAK were determined by real-time PCR, Western blot and immunohistochemistry. The overexpression of lncRNA 9708-1 significantly decreased the fungal load from Day 4 to 7. H&E staining indicated that the impaired histological profiles were improved in lncRNA 9708-1-overexpressed group. LncRNA 9708-1 led to a significant increase in FAK level of vagina tissue which is expressed mainly in epithelial basal layer. This study suggests that lncRNA 9708-1 played a protective role on murine experimental VVC by upregulating the expression levels of FAK.

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