Development and characterization of oral lipid-based Amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans

Wasan, Ellen K.; Bartlett, Karen H.; Gershkovich, Pavel; Sivak, Olena; Banno, Brian; Wong, Zhao; Gagnon, Jeffrey; Gates, Byron D.; León, Carlos; Wasan, Kishor M.

doi:10.1016/j.ijpharm.2009.01.003

Cited by 104 publications

(73 citation statements)

References 15 publications

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“…SMEDDS can improve oral bioavailability by enhancing permeation across the intestinal membrane, solubilization, a reduced or eliminated effect of food, droplet size reduction, lymphatic transport, and improvement of drug dissolution. [26][27][28] Moreover, the enhancement of oral absorption of 25-OCH 3 -PPD-loaded SMEDDS compared with 25-OCH 3 -PPD suspension in our study was likely to be due to the effects of the surfactants and cosurfactants, including improved mucosal permeability, smaller droplets, and greater surface area. Double C max peaks for 25-OCH 3 -PPD and 25-OH-PPD were observed after administration of SMEDDS ( Figures 4 and 5).…”

Section: In Vivo Absorption Studiesmentioning

confidence: 73%

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Cai¹,

Shi²,

Zhang³

et al. 2014

IJN

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The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3β;12β;20-triol (25-OCH 3 -PPD). Optimized SMEDDS formulations for 25-OCH 3 -PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH 3 -PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH 3 -PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH 3 -PPD via the oral route.

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Section: In Vivo Absorption Studiesmentioning

confidence: 73%

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Cai¹,

Shi²,

Zhang³

et al. 2014

IJN

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“…Glyceryl monooleate (type 40), a readily dispersible and lymphotropic solubilizing agent composed mainly of a mixture of monoand diglycerides of oleic acid, had been used in the selfemulsifying drug delivery system by other researchers. 29,30 Moreover, Diethylene glycol monoethyl ether showed the largest solubility (236.29±21 mg/mL) as compared with the other cosurfactants ( Figure 5B). Diethylene glycol monoethyl ether, a highly purified diethylene glycol monoethyl ether, was often employed in the SNEDDS formulation as a coemulsifier or solubilizer for actives.…”

Section: Characterization Of Apcmentioning

confidence: 94%

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex

Shen¹,

Bi²,

Tian³

et al. 2016

IJN

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Background Akebia saponin D (ASD) exerts various pharmacological activities but with poor oral bioavailability. In this study, a self-nanoemulsifying drug delivery system (SNEDDS) based on the drug–phospholipid complex technique was developed to improve the oral absorption of ASD. Methods ASD–phospholipid complex (APC) was prepared using a solvent-evaporation method and characterized by infrared spectroscopy, differential scanning calorimetry, morphology observation, and solubility test. Oil and cosurfactant were selected according to their ability to dissolve APC, while surfactant was chosen based on its emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were constructed to determine the optimized APC-SNEDDS formulation, which was characterized by droplet size determination, zeta potential determination, and morphology observation. Robustness to dilution and thermodynamic stability of optimized formulation were also evaluated. Subsequently, pharmacokinetic parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated in rats. Results The liposolubility significantly increased 11.4-fold after formation of APC, which was verified by the solubility test in n -octanol. Peceol (Glyceryl monooleate [type 40]), Cremophor ® EL (Polyoxyl 35 castor oil), and Transcutol HP (Diethylene glycol monoethyl ether) were selected as oil, surfactant, and cosurfactant, respectively. The optimal formulation was composed of Glyceryl monooleate (type 40), Polyoxyl 35 castor oil, Diethylene glycol monoethyl ether, and APC (1:4.5:4.5:1.74, w/w/w/w), which showed a particle size of 148.0±2.7 nm and a zeta potential of −13.7±0.92 mV after dilution with distilled water at a ratio of 1:100 (w/w) and good colloidal stability. Pharmacokinetic studies showed that APC-SNEDDS exhibited a significantly greater C max 1 (733.4±203.8 ng/mL) than ASD (437.2±174.2 ng/mL), and a greater C max 2 (985.8±366.6 ng/mL) than ASD (180.5±75.1 ng/mL) and APC (549.7±113.5 ng/mL). Compared with ASD, T max 1 and T max 2 were both remarkably shortened by APC-SNEDDS. The oral bioavailability in rats was enhanced significantly to 183.8% and 431.8% by APC and APC-SNEDDS, respectively. Conclusion These results indicated that APC-SNEDDS was a promising drug delivery system to enhance the oral bioavailability of ASD.

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“…8 GMO is a safe and cheap lipid excipient, and is regarded as the better alternative for oral administration, compared against other lipid excipients (PHY, DOPS, etc). 14 Therefore, the purpose of this study was to investigate the GMO cubosomal formulation for AmB oral administration, focusing on antifungal efficacy in vivo and cellular mechanisms of a human colon adenocarcinoma cell line (Caco-2).…”

Section: Introductionmentioning

confidence: 99%

Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

Yang¹,

Chen²,

Yang³

et al. 2014

IJN

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The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone®, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.

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Development and characterization of oral lipid-based Amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans

Cited by 104 publications

References 15 publications

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex

Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

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Development and characterization of oral lipid-based Amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans

Cited by 104 publications

References 15 publications

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3&beta;, 12&beta;, 20-triol: preparation and evaluation

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3&beta;, 12&beta;, 20-triol: preparation and evaluation

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D&ndash;phospholipid complex

Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

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Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex