Encapsulation of amphotericin B in poly(ethylene glycol)-block-poly(ɛ-caprolactone-co-trimethylenecarbonate) polymeric micelles

Vandermeulen, Gaëlle; Rouxhet, Laurence; Ariën, Albertina; Brewster, Marcus E.; Préat, Véronique

doi:10.1016/j.ijpharm.2005.11.031

Cited by 75 publications

(63 citation statements)

References 22 publications

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“…Investigators have employed different watersoluble polymers to develop encapsulated, conjugated AmBbased delivery systems, but have met with little success. [40][41][42][43][44][45][46][47][48] In some of the earlier efforts, polymers synergized the toxicity of AmB, 49 while in others the AmB was unable to retain the beneficial physicochemical properties associated with its liposomal form (AmB-L). 50 Although, AmB-cyclodextrin complexes showed improved water solubility, 49,51 they were found to be toxic to human red blood cells.…”

Section: Resultsmentioning

confidence: 99%

“…54 Polymeric micelle systems have also been developed; however, encapsulation in the polymeric micelles decreased the in vitro antifungal activity of the drug. 40 Moreover, these micelles have been shown to be unstable in the presence of serum due to disruption of their integrity, 55 resulting in rapid and near-complete release of core-loaded molecules from circulating micelles in an uncontrolled fashion. 56 Herein, we aimed to develop a stable, easy-to-prepare, nontoxic preparation of AmB with physicochemical characteristics comparable with those shown by AmB-L.…”

Section: Resultsmentioning

confidence: 99%

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Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

Zia¹,

Khan²,

Zubair³

et al. 2015

IJN

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In the present study, we developed a self-assembled biodegradable polyglutamic acid (PGA)-based formulation of amphotericin B (AmB) and evaluated its in vitro antifungal potential against Candida albicans . The AmB-loaded PGA nanoparticles were prepared in-house and had a mean size dimension of around 98±2 nm with a zeta potential of −35.2±7.3 mV. Spectroscopic studies revealed that the drug predominantly acquires an aggregated form inside the formulation with an aggregation ratio above 2. The PGA-based AmB formulation was shown to be highly stable in phosphate-buffered saline as well as in serum (only 10%–20% of the drug was released after 10 days). The AmB–PGA nanoparticles were less toxic to red blood cells (<15% lysis at an AmB concentration of 100 μg/mL after 24 hours) when compared with Fungizone ® , a commercial antifungal product. An MTT assay showed that the viability of mammalian cells (KB and RAW 264.7) was negligibly affected at AmB concentrations as high as 200 μg/mL. Histopathological examination of mouse kidney revealed no signs of tissue necrosis. The AmB–PGA formulation showed potent antimicrobial activity similar to that of Fungizone against C. albicans . Interestingly, AmB-bearing PGA nanoparticles were found to inhibit biofilm formation to a considerable extent. In summary, AmB–PGA nanoparticles showed highly attenuated toxicity when compared with Fungizone, while retaining equivalent active antifungal properties. This study indicates that the AmB–PGA preparation could be a promising treatment for various fungal infections.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

Zia¹,

Khan²,

Zubair³

et al. 2015

IJN

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“…45,46 In aqueous solutions, amphotericin B exists in an aggregated form containing about 2,000 molecules, whereas in DMSO the monomeric form is predominant below 5 mM. 47 The characteristic absorption bands in UV and CD spectroscopic methods can differentiate between the different states of aggregation.…”

Section: Gelatin Stabilizes the Monomeric Forms Of Amphotericin Bmentioning

confidence: 99%

Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

Lakshminarayanan

Sridhar

Loh

et al. 2014

IJN

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Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections.

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“…However, the infusion toxicity and nephrotoxicity, which may ascribe to the dimeric form obtained with DOC, using a technological process with pH changes, still frequently cause troublesome complications. [11][12][13] Commercial products, including a lipid complex (Abelcet ® , Sigma-Tau, Gaithersburg, MD, USA) and a liposomal product (Ambisome ® , Astellas, Tokyo, Japan) that encapsulate AmB with hydrogenated soybean lecithin, phosphatidylcholine, and cholesterol (polyaggregate forms), have already come to the market. The toxicity incidence of these formulations becomes lower, and they are accepted well when administered in higher doses.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and evaluation of amphotericin B-loaded MPEG-PCL-g-PEI micelles for local treatment of oral <em>Candida albicans</em>

Zhou¹,

Zhang²,

Chen³

et al. 2017

IJN

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Fatal Candida albicans infections in the mucosal system can occur in association with immune-compromised diseases and dysbacteriosis. Currently, amphotericin B (AmB) is considered to be the most effective antibiotic in the treatment of C. albicans infections, but its clinical application is limited by side effects and poor bioavailability. In order to use AmB in the local treatment of oral C. albicans infections, AmB/MPEG-PCL-g-PEI (monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone)-graft-polyethylenimine, MPP) micelles were prepared. A series of characterizations were performed. The micelles allowed a sustained in vitro release in both normal oral conditions (pH 6.8) and C. albicans infection conditions (pH 5.8). Then, buccal tablets containing freeze-dried powder of AmB/MPP micelles were produced by direct compression process and evaluated as regards to weight variation, hardness, and friability. In vitro drug release of the buccal tablets was measured in both the United States Pharmacopeia dissolution apparatus and the dissolution rate test apparatus, which was previously designed for simulating in vivo conditions of the oral cavity. The buccal tablets could sustainably release within 8 h and meet the antifungal requirements. Regarding safety assessment of AmB/MPP micelles, in vivo histopathological data showed no irritation toward buccal mucosa of the rats in both optical microscopy and ultrastructure observation of the tissues. MTT experiment proved that AmB/MPP micelles reduced the cytotoxicity of AmB. The micelles delivered through the gastrointestinal route were also found to be non-systemic toxicity by liquid chromatography-mass spectrometry analysis. Furthermore, the antifungal action of AmB/MPP micelles was evaluated. Although AmB/MPP had no obvious improvement as compared to AmB alone in the antifungal effect on planktonic C. albicans , the micelles significantly enhanced the antifungal activity against the biofilm state of C. albicans . Thus, it was concluded that AmB/MPP micelles represent a promising novel drug delivery system for the local treatment of oral C. albicans infections.

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Encapsulation of amphotericin B in poly(ethylene glycol)-block-poly(ɛ-caprolactone-co-trimethylenecarbonate) polymeric micelles

Cited by 75 publications

References 22 publications

Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

Preparation, characterization, and evaluation of amphotericin B-loaded MPEG-PCL-g-PEI micelles for local treatment of oral <em>Candida albicans</em>

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