Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

Veloso, Danillo Fabrini Maciel Costa; Benedetti, Naiara I. G. M.; Ávila, Renato Ivan de; Bastos, Thiago Souza Azeredo; Silva, Thaísa C.; Silva, Maria R. R.; Batista, Aline Carvalho; Valadares, Marize Campos; Lima, Eliana Martins

doi:10.1080/10717544.2018.1492046

Cited by 52 publications

(26 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…VRC-PNs Ocu displayed superior antifungal activity against Candida albicans (more susceptible) than Aspergillus nidulans. 66 Therefore, HPMC promotes corneal drug permeation as manifested from the microbiological confirmation. VRC-PNs Ocu containing HPMC as a viscosity modifier slow down the growth of fungi.…”

Section: Microbiological Study Antifungal Susceptibility Testingmentioning

confidence: 99%

<p>Ocular Inserts of Voriconazole-Loaded Proniosomal Gels: Formulation, Evaluation and Microbiological Studies</p>

El-Emam¹,

Girgis²,

El‐Sokkary³

et al. 2020

IJN

View full text Add to dashboard Cite

Background: Voriconazole (VRC) is a triazole broad spectrum antifungal drug, used in the management of versatile fungal infections, particularly fungal keratitis. The obligatory use of niosomal delivery of VRC may reduce the frequency of dosing intervals resulting from its short biological half time and consequently improve patient compliance. Methods: VRC loaded proniosomes (VRC-PNs) were set by the coacervation technique and completely characterized. The developed formula was comprehensively assessed concerning in-vitro release behavior, kinetic investigation, and its conflict against refrigerated and room temperature conditions. A selected noisomal formula was incorporated into ocusert (VRC-PNs Ocu) formulated by 1% w/w hydroxypropyl methyl cellulose HPMC and 0.1% w/w carbopol 940. Eventually, in vitro antifungal activity against Candida albicans and Aspergillus nidulans was assessed by the cup diffusion method. Results: The optimized VRC-PNs (Pluronic F127: cholesterol weight ratio 1:1 w/w) exhibited the highest entrapment efficiency (87.4±2.55%) with a spherical shape, proper size in nano range and a suitable Zeta potential of 209.7±8.13 nm and −33.5±1.85 mV, respectively. Assurance of drug encapsulation in nanovesicles was accomplished by several means such as attenuated total reflection Fourier-transform infrared spectroscopy, differential scanning calorimetry in addition to powder X-ray diffraction investigations. It displayed a biphasic in vitro release pattern and after 6 months of storage at a refrigerated temperature, the optimized formula preserved its stability. VRC-PNs Ocu proved a very highly significant antifungal activity matched with the free drug or nanosuspension which was extra assured by comparing its mean inhibition zone with that of 5% natamycin market eye drops. Conclusion: In conclusion, VRC-PNs Ocu could be considered as a promising stable sustained release topical ocular nanoparticulate system for the management of fungal infections.

show abstract

Section: Microbiological Study Antifungal Susceptibility Testingmentioning

confidence: 99%

<p>Ocular Inserts of Voriconazole-Loaded Proniosomal Gels: Formulation, Evaluation and Microbiological Studies</p>

El-Emam¹,

Girgis²,

El‐Sokkary³

et al. 2020

IJN

View full text Add to dashboard Cite

show abstract

“…However, the systemic administration of VCZ is associated with serious adverse effects and drug interactions (Theuretzbacher et al., 2006 ). VCZ has molecular weight of 349.3 and log P value of 1.8 making it a suitable candidate for ocular drug delivery with good corneal permeation (de Sá et al., 2015 ; Veloso et al., 2018 ). However, no commercial ocular product of VCZ is available yet, possibly due to the limited aqueous solubility of VCZ.…”

Section: Introductionmentioning

confidence: 99%

Statistical optimization of hyaluronic acid enriched ultradeformable elastosomes for ocular delivery of voriconazole via Box-Behnken design: in vitro characterization and in vivo evaluation

et al. 2020

View full text Add to dashboard Cite

Voriconazole (VCZ) is a well-known broad spectrum triazole antifungal, mainly used orally and intravenously. The study aimed to formulate VCZ into ultradeformable elastosomes for the topical treatment of ocular fungal keratitis. Different formulae were prepared using a modified ethanol injection method, employing a 3 3 Box-Behnken design. They were characterized by measuring their entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The optimized formula was subjected to further in vitro investigations and in vivo evaluation studies. The prepared vesicles had satisfactory EE%, PS, PDI and ZP values. The numerical optimization process suggested an optimal elastosomal formula (OE) composed of phosphatidyl choline and brij S100 at the weight ratio of 3.62: 1, 0.25%w/v hyaluronic acid and 5% (percentage from phosphatidyl choline/brij mixture) polyvinyl alcohol. It had high EE (72.6%), acceptable PS and PDI (362.4 nm and 0.25, respectively) and highly negative ZP of −41.7 mV. OE exhibited higher elasticity than conventional liposomes, with acceptable stability for three months. Transmission electron microscopy demonstrated the spherical morphology of vesicles with an external transparent coat of Hyaluronic acid. OE was expected to cause no ocular irritation or blurring in vision as reflected by pH and refractive index measurements. The histopathological study revealed the safety of OE for ocular use. The fungal susceptibility testing using Candida albicans demonstrated the superiority of OE to VCZ suspension, with greater and more durable growth inhibition. Therefore, OE can be regarded as a promising formula, achieving both safety and efficacy.

show abstract

“…Crosslinking of chitosan derivatives to obtain gels is widely used, especially with external crosslinkers (i.e., aldehydes), which usually exhibit a harmful and/or toxic character in nature [19]. On the other hand, crosslinking with the freeze–thaw process is simple, easy to perform, and it does not need addition of any crosslinking agent to prepare gels [18,20].…”

Section: Introductionmentioning

confidence: 99%

Chitosan-Graft-Poly(N-Isopropylacrylamide)/PVA Cryogels as Carriers for Mucosal Delivery of Voriconazole

et al. 2019

View full text Add to dashboard Cite

The objective of this study was to prepare and characterize physically crosslinked gel formulations of chitosan (CS)-graft-poly(N-isopropyl acrylamide) (PNIPAAm) and polyvinyl alcohol (PVA) for smart delivery of an antifungal drug, Voriconazole, for mucosal applications. For this purpose, cryogels of CS-g-PNIPAAm/PVA and CS/PVA were tested by means of texture profile analysis and rheology to determine optimal matrix properties for topical application. The ratio of 75/25 v/v % CS-g-PNIPAAm/PVA was selected to be used for formulation since it gave low compressibility and hardness (1.2 and 0.6 N) as well as high adhesion properties and non-Newtonian flow behavior. The cryogels and formulations were further characterized by means of FTIR spectroscopy, swelling behavior, texture analysis, scanning electron microscopy (SEM), thermal (differential scanning calorimetry (DSC) and TGA), and rheological behavior. The drug loading capacity and in vitro release profile of the drug, storage stability, and cytotoxicity tests were also performed for the gel formulation. The FTIR, DSC, and TGA results verified the successful formation of cryogels. Swelling studies revealed a pH-dependent swelling ability with a maximum swelling degree of 1200% in acid and 990% in phosphate buffer (pH = 7.4). Thermal studies showed that CS-g-PNIPAAm/PVA 75/25 had higher thermal stability proving the structural complexity of the polymer. The loading capacity of Voriconazole was found to be 70% (w/w). The in vitro release profiles of Voriconazole showed Fickian release behavior for CS-g-PNIPAAm/PVA 75/25 gel with an approximate delivery of 38% within 8 h, slower than matrices containing unmodified chitosan. The storage stability test exhibited that the gel formulation was still stable even after aging for two months. Moreover, the cell culture assays revealed a non-toxic character of the polymeric matrix. Overall results showed that the CS-g-PNIPAAm/PVA 75/25 hydrogel has the potential to be used as a smart polymeric vehicle for topical applications.

show abstract

Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

Cited by 52 publications

References 61 publications

<p>Ocular Inserts of Voriconazole-Loaded Proniosomal Gels: Formulation, Evaluation and Microbiological Studies</p>

<p>Ocular Inserts of Voriconazole-Loaded Proniosomal Gels: Formulation, Evaluation and Microbiological Studies</p>

Statistical optimization of hyaluronic acid enriched ultradeformable elastosomes for ocular delivery of voriconazole via Box-Behnken design: in vitro characterization and in vivo evaluation

Chitosan-Graft-Poly(N-Isopropylacrylamide)/PVA Cryogels as Carriers for Mucosal Delivery of Voriconazole

Contact Info

Product

Resources

About