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

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.

Download Full-text

Bioassay-guided optimization of lipid-based erythromycin microparticles

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i7.2 ◽

2020 ◽

Vol 19 (7) ◽

pp. 1351-1358

Author(s):

Ifeanyi T. Nzekwe ◽

Anselm C. Okere ◽

Ifeanyi E. Okoye ◽

Kokonne E. Ekere ◽

Adaobi A. Ezenwa ◽

...

Keyword(s):

Ex Vivo ◽

Drug Loading ◽

Entrapment Efficiency ◽

Antimicrobial Activities ◽

Hydrodynamic Size ◽

Chemical Assay ◽

Acid Ratio ◽

Drug Entrapment Efficiency ◽

Lower Variation

Purpose: To optimize erythromycin microparticles by in vitro bioassay methods based on its antibacterial activity. Methods: The microparticles were produced by high shear homogenization. The effects of different lipid-to-surfactant ratios were studied. The hydrodynamic size of the different batches was evaluated using dynamic light scattering while bioactive drug load per batch was assessed in agar using bioassay methods. The antimicrobial activities of selected batches were tested ex vivo by determination of reduction in bacteraemia following administration of the microparticles to infected animals. Results: All batches had particles with hydrodynamic sizes < 8.5 microns. Batch 7 with a 2: 5: 2.5 (drug: surfactant: stearic acid) ratio, represents the optimized batch with a hydrodynamic size of 2281 nm, a bioactive drug loading capacity (BLC) of 4.67 ± 0.70 % and bioactive drug entrapment efficiency (BEE) of 10.51 %. The “microparticle MIC” against Staphylococcus aureus was 1.74 x 10-3 μg/ml. Despite containing lower amounts of erythromycin than the pure sample, the microparticles achieved comparable reduction in bacteraemia, with the optimized batch exhibiting lower variation in bacteraemia than the pure drug. Conclusion: Erythromycin microparticles have been successfully optimized with the aid of bioassay methods which has the advantage that only the bioactive drug concentration is factored in. This method eliminates problems posed by inadequate or non-discriminating chemical assay methods. Keywords: Microparticles, Erythromycin, Gastrointestinal, Bioavailability Antimicrobial, Bioactivity, Encapsulation

Download Full-text

Nanopartículas lipídicas sólidas contendo óleo essencial de Melaleuca alternifolia Cheel como plataforma inovadora no tratamento da candidíase orofaríngea

10.34019/ufjf/te/2021/00007 ◽

2021 ◽

Author(s):

◽

Hanny Reis Mockdeci Gonçalves

Keyword(s):

Ex Vivo ◽

Melaleuca Alternifolia ◽

Candida Spp

Espécies do gênero Candida spp. são frequentemente encontradas na microbiota bucal vivendo de forma comensal; mas podem mudar para o estado patogênico e gerar candidíase orofaríngea, que pode evoluir para candidemia. Apesar da importância clínica e epidemiológica dessas infecções, as opções terapêuticas são limitadas, o que tem estimulado a busca por novos medicamentos, dentre eles os de origem vegetal e o emprego da nanotecnologia como estratégia tecnológica. Nesse contexto, o presente estudo teve como objetivo desenvolver uma plataforma inovadora para o tratamento da candidíase orofaríngea, constituída por um hidrogel contendo o óleo de Melaleuca alternifolia Cheel (OM) encapsulado em nanopartículas lipídicas sólidas (NLS). A composição química do óleo foi avaliada por cromatografia gasosa acoplada à espectrometria de massas. As NLS foram caracterizadas em relação ao tamanho hidrodinâmico médio das partículas (TP), índice de polidispersividade (PdI), potencial Zeta (PZ), eficiência de encapsulação (EE), morfologia, estabilidade, potencial antioxidante e citotoxicidade in vitro em linhagem celular de fibroblastos murinos (L929). As NLS contendo OM (OM-NLS) foram incorporadas em hidrogel e, em seguida, verificou-se a atividade antifúngica frente a leveduras padrão de C. albicans, C. glabrata, C. krusei e C. guilliermondii. Por fim, a permeação ex vivo do OM a partir do hidrogel, utilizando mucosa jugal suína foi analisada. Foram identificados treze constituintes no OM, cuja composição percentual atendeu aos padrões descritos pela ISO 4730: 2017. Quanto à caracterização das OM-NLS, os valores para TP, PdI e PZ foram 135,9 ± 6,65; 0,19 ± 0,04 e -31,07 ± 1,05, respectivamente. As OM-NLS mostraram uma EE de 92,74% ± 0,012% e revelaram uma forma esférica. Além disso, a atividade antioxidante variou de 14,1% a 17,2% e foi encontrado efeito citotóxico contra a linhagem celular L929 (IC50 = 77,4 µg/mL). Por pelo menos 120 dias, não foram observadas mudanças significativas nos valores da média de TP e PdI para OM-NLS, e o hidrogel contendo OM-NLS permaneceu estável por minimamente 30 dias, ambos sob refrigeração. OM-NLS e hidrogel contendo OM-NLS exibiram efeito fungicida (concentração fungicida mínima variou entre 5,60 e 11,20 mg/mL; e 5,53 e 11,06 mg/mL, respectivamente); e permeação transmucosa (70,52% ± 3,85%). Concluiu-se que o hidrogel contendo OM-NLS apresentou efeito fungicida superando o OM, estabilidade durante o período de avaliação e foi permeável pela mucosa jugal suína, podendo ser, portanto um sistema de entrega promissor na candidíase orofaríngea.

Download Full-text

Characterization of bilayered matrix-type mucoadhesive buccal films containing tizanidine hydrochloride and piroxicam

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i11.1 ◽

2021 ◽

Vol 20 (11) ◽

pp. 2241-2248

Author(s):

M. Yasmin Begum ◽

Ali Alqahtani

Keyword(s):

Drug Release ◽

Patient Compliance ◽

Residence Time ◽

Ex Vivo ◽

Drug Bioavailability ◽

In Vitro Drug Release ◽

Surface Ph ◽

Folding Endurance ◽

Buccal Films

Purpose: To formulate and characterize tizanidine hydrochloride (TZN) and piroxicam (PRX)-loaded bilayer mucoadhesive buccal films with an intention to improve the bioavailability and patient compliance in pain management.Methods: Bilayer buccal films were prepared by solvent evaporation technique using hydroxypropyl methylcellulose (HPMC) 15cps and polyvinylpyrrolidone (PVP K30 as immediate release (IR) layer forming polymers and HPMC K15 M, PVP K 90 along with various muco adhesive polymers (Carbopol P934, sodium alginate, etc), as sustained release (SR) layer forming polymers. The prepared films werecharacterized for thickness, weight variation, folding endurance, surface pH, swelling index,mucoadhesive strength, in vitro residence time, in vitro drug release, ex vivo permeation and drug release kinetics.Results: The prepared films were of largely uniform thickness, weight and drug content. Moisture loss (%) and folding endurance were satisfactory. Surface pH was compatible with salivary fluid. Disintegration time was 85 s for F1 and 115 s for F2 of IR films. In vitro dissolution studies showed 99.12 ± 1.2 % (F1) and 90.36 ± 1.8 % (F2) were released in 45 min. Based on the above results, F1 was chosen as the optimum formulation to be combined with SR layer of TZN. Amongst the SR layers of TZN in vitro drug release. The findings show that of F2 was 98.38 ± 0.82 % and correlated with ex vivo release. Drug release followed zero order release kinetics and mechanism of drug release was non-Fickian type diffusion. In vitro residence time was greater than 5 h.Conclusion: The findings show that the bilayer buccal films demonstrate the dual impact of deliveringPRX instantly from the IR layer, with good controlled release and permeation of TZN from the SR layer, thus providing enhanced therapeutic efficacy, drug bioavailability and patient compliance.

Download Full-text

Development of a Topical Amphotericin B and Bursera graveolens Essential Oil-Loaded Gel for the Treatment of Dermal Candidiasis

Pharmaceuticals ◽

10.3390/ph14101033 ◽

2021 ◽

Vol 14 (10) ◽

pp. 1033

Author(s):

Lupe Carolina Espinoza ◽

Lilian Sosa ◽

Paulo C. Granda ◽

Nuria Bozal ◽

Natalia Díaz-Garrido ◽

...

Keyword(s):

Essential Oil ◽

Amphotericin B ◽

Ex Vivo ◽

In Vitro Release ◽

Topical Administration ◽

In Vivo Models ◽

Topical Gel ◽

Cutaneous Candidiasis ◽

Vitro Release

The higher molecular weight and low solubility of amphotericin B (AmB) hinders its topical administration. The aim of this study was to incorporate Bursera graveolens essential oil into an AmB topical gel (AmB + BGEO gel) in order to promote the diffusion of the drug through the skin in the treatment of cutaneous candidiasis. AmB + BGEO gel formulation was determined using a factorial experiment. Physical and chemical parameters, stability, in vitro release profile and ex vivo permeation in human skin were evaluated. In vitro antimicrobial activity was studied using strains of C. albicans, C. glabrata and C. parapsilosis. The tolerability was evaluated using in vitro and in vivo models. AmB + BGEO gel presented appropriate characteristics for topical administration, including pH of 5.85, pseudoplastic behavior, optimal extensibility, as well as high stability and acceptable tolerability. In vitro release studies showed that the formulation releases the drug following a Boltzmann sigmoidal model. Finally, AmB + BGEO gel exhibited higher amount of drug retained inside the skin and lower Minimum Inhibitory Concentration than a formulation sans essential oil. Therefore, these results suggest that the incorporation of B. graveolens essential oil in the formulation could be used as strategy to promote a local effect in the treatment of cutaneous candidiasis.

Download Full-text

Accuracy in clinical examinations for the diagnosis of vulvovaginitis by CANDIDA SPP. and IN VITRO susceptibility to the main antifungals

Revista de Patologia Tropical / Journal of Tropical Pathology ◽

10.5216/rpt.v49i3.64233 ◽

2020 ◽

Vol 49 (3) ◽

Author(s):

Andressa Santana Santos ◽

Ana Laura Sene Amancio Zara ◽

Fábio Silvestre Ataídes ◽

Elisangela Gomes da Silva ◽

Vivianny Aparecida Queiroz Freitas ◽

...

Keyword(s):

Amphotericin B ◽

Clinical Diagnosis ◽

High Resistance ◽

Antifungal Susceptibility ◽

Vulvovaginal Candidiasis ◽

Vaginal Mucosa ◽

Candida Spp ◽

In Vitro Susceptibility ◽

Gynecology And Obstetrics

Vulvovaginal candidiasis (VVC) is a common infection. This work aims to determine the positive predictive value (PPV) of the clinical diagnosis of VVC and to characterize Candida species isolated from the vaginal mucosa. This cross-sectional study was conducted from February 2016 to February 2017 at the Gynecology and Obstetrics Outpatient Clinic of the Hospital das Clínicas, in Goiânia, Goiás State, Brazil. The study included samples of vaginal secretion from 55 women who complained of vaginal discharge and itching as their main symptoms. The PPV of the clinical diagnosis of VVC was estimated in comparison to the laboratory culture method. The phenotypic methods and molecular tests were performed to identify Candida spp. In vitro susceptibility of Candida spp. isolates to fluconazole, itraconazole, clotrimazole, nystatin, and amphotericin B was determined using the broth microdilution assay. Yeast growth using the enzymes protease, phospholipase, and hemolysin was carried out in media containing respectively bovine albumin, egg yolk, and sheep erythrocytes. A PPV of 61.8% (34/55) was determined. Among the 55 vulvovaginal samples collected, we identified 36 isolates in whichC. albicans was the most common species. High resistance to fluconazole and low minimal inhibitory concentration (MIC) values for clotrimazole, nystatin and amphotericin B were observed. All isolates were proteinase and hemolysin producers, while seven strains were phospholipase negative. The clinical diagnosis of VVC presented a moderate PPV, which meant that cultures had to be conducted in the laboratory to confirm infection. The high resistance to fluconazole and itraconazole indicated the importance of the in vitro susceptibility test.KEY WORDS: Vulvovaginal candidiasis; antifungal susceptibility; enzymatic activity

Download Full-text

In vitro activity of BMS-181184 compared with those of fluconazole and amphotericin B against various candida spp.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2229 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2229-2231 ◽

Cited By ~ 9

Author(s):

H M Wardle ◽

D Law ◽

D W Denning

Keyword(s):

High Resolution ◽

Amphotericin B ◽

Clinical Studies ◽

Antifungal Agents ◽

Vitro Activity ◽

In Vitro Activity ◽

Candida Spp ◽

New Class ◽

Microdilution Method

We compared the in vitro activity of BMS-181184, the first compound of a new class of antifungal agents, the pradimicins, with those of fluconazole and amphotericin B against 64 clinical isolates of Candida species. MICs were determined by a microdilution method with high resolution medium for BMS-181184 and fluconazole and antibiotic medium no. 3 with 2% glucose for amphotericin B. MICs of BMS-181184 for all yeasts were in the range of 0.78 to 12.5 micrograms/ml. BMS-181184 was active against isolates resistant to other antifungal agents, consistent with a novel mode of action. Minimum fungicidal concentrations for 16 isolates showed that BMS-181184 was fungicidal. Clinical studies are now required to confirm its activity.

Download Full-text

Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis

Pharmaceutics ◽

10.3390/pharmaceutics11070312 ◽

2019 ◽

Vol 11 (7) ◽

pp. 312 ◽

Cited By ~ 7

Author(s):

Lilian Sosa ◽

Ana Cristina Calpena ◽

Marcelle Silva-Abreu ◽

Lupe Carolina Espinoza ◽

María Rincón ◽

...

Keyword(s):

Drug Release ◽

Amphotericin B ◽

Ex Vivo ◽

Skin Irritation ◽

Vaginal Candidiasis ◽

Vaginal Mucosa ◽

High Porosity ◽

Candida Spp ◽

Thermoreversible Gel ◽

Antifungal Efficacy

The present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue layer in order to provide a local effect. Parameters including internal structure, swelling, porosity, and short-term stability were determined. In addition, drug release profile and ex vivo skin and vaginal permeation studies were carried out. Antifungal efficacy was evaluated against strains of Candida spp. and atomic force microscopy (AFM) supported the results. The tolerance of AmB-gel was studied by evaluating biomechanical properties of skin and determining the irritation level in scarified rabbit skin supported by histological analysis. Results confirmed the development of a thermoreversible AmB-gel with high porosity exhibiting Newtonian behavior at 4 °C and pseudoplasticity at 32 °C as well as optimal stability for at least 90 days. The Amb-gel provided a sustained drug release following a Boltzmann sigmoidal model. Non permeation was observed in skin and vaginal mucosa, showing a high retained amount of AmB of 960.0 and 737.3 µg/g/cm2, respectively. In vitro antifungal efficacy showed that AmB-gel was more effective than Free-AmB in inhibiting strains of Candida spp. and these results were corroborated by AFM. Finally, tolerance studies showed that its application did not induce skin irritation nor alter its biophysical properties. Together, these results confirmed that AmB-gel could be proposed as a promising candidate for the clinical status in the treatment of skin and vaginal candidiasis.

Download Full-text

Novel Polypseudorotaxanes Hydrogel based Nail Lacquer of Efinaconazole for Transungual Drug Delivery

Drug Delivery Letters ◽

10.2174/2210303110999200918163213 ◽

2020 ◽

Vol 10 ◽

Author(s):

Rohan Aggarwal ◽

Monika Targhotra ◽

Bhumika Kumar ◽

P. K. Sahoo ◽

Meenakshi K. Chauhan

Keyword(s):

Drug Delivery ◽

Ex Vivo ◽

Sol Gel ◽

Nail Plate ◽

Penetration Enhancer ◽

High Rate ◽

Poloxamer 407 ◽

Drying Time ◽

Nail Lacquer ◽

Transungual Delivery

Aim: Due to the various drawbacks associated with current treatment therapy of onychomycosis, the main aim was to develop thermosensitive hydrogels and thermosensitive polypseudorotaxanes hydrogels-based nail lacquer for transungual delivery of Efinaconazole for management of onychomycosis. The objective is to enhance the permeation and retention of the drug in the nails and improve patient compliance. Method: Poloxamer 407 and Hydroxy Propyl -β- cyclodextrin was used to prepare the nail lacquers. 2-mercaptoethanol was added as a penetration enhancer to improve the penetration of the drug across the nail plate. The formulations were optimized by varying the concentration of poloxamer and water:ethanol ratio and evaluated based on basis of drying time, sol-gel transition temperature, ex vivo drug release and viscosity. The optimized formulation was further evaluated for pH, water resistance, non-volatile content, drug content, blush test, spreadability, and stability studies. Results: The increase in ethanol concentration, reduction in poloxamer proportion lead to reduction in lacquer stickiness thus, improving the lacquer drying time and penetration. The polypseudorotaxanes improved the permeation profile of the drug in comparison to the marketed nail lacquer. The presence of 2-mercaptoethanol also contributed in transungual delivery of Efinaconazole. Conclusion:: The polypseudorotaxanes based nail lacquer with the incorporation of penetration enhancer was able to achieve a high rate of drug penetration and retention, thus supporting the potential use of aqueous based-nail lacquer in transungual drug delivery for the onychomycosis treatment.

Download Full-text

Formulation and Ex-vivo Evaluation of Transdermal Patches of Glipizide using the Penetration Enhancer Buchanania- Lanzan (Spreng) Seed Oil

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.1.9 ◽

2015 ◽

Vol 8 (1) ◽

pp. 2768-2774

Author(s):

Sudarshan Singh ◽

Sunil B Bothara ◽

D. Roshan Patel ◽

Mahobia K Naveen

Keyword(s):

Essential Oils ◽

Seed Oil ◽

Ex Vivo ◽

Drug Loading ◽

Penetration Enhancers ◽

Permeation Enhancement ◽

Dsc Studies ◽

Transdermal Patches ◽

Effective Stability

The aim of the present work was to evaluate the permeation enhancement properties of Buchanania lanzan spreng seed oil. Ethyl cellulose transdermal patches of Glipizide using some essential oils as penetration enhancers were developed. Effect of drug loading and penetration enhancers on the in vitro permeation of drug through rat skin was investigated. Incorporation of essential oils enhanced the moisture content, moisture uptake capacity and permeation of Glipizide across skin barriers. Among the penetration enhancers used, Buchanania lanzan spreng seed oil found to be most effective. Stability as well FTIR and DSC studies did not show any Interaction/degradation of the drug. It was concluded that stable and effective Glipizide transdermal patches can be prepared using essential oils as penetration enhancers. Further it was also concludes that the seed oil can be used in permeation enhancement of various types of tropical preparation.

Download Full-text