Poly(L-lactide) Nanoparticles Reduce Amphotericin B Cytotoxicity and Maintain Its &lt;I&gt;In Vitro&lt;/I&gt; Antifungal Activity

Casa, Diani Meza; Camargo, Luciana Erzinger Alves de; Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

doi:10.1166/jnn.2015.9177

Cited by 35 publications

(12 citation statements)

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“…[28][29][30] First, 10 mg of AmB and 100 mg of MPP triblock copolymer were co-dissolved in 200 mL methanol with the help of ultrasound. The methanol was recovered by evaporating at 55°C under reduced pressure (RE-52A; Shanghai Ya Rong Biochemistry Instrument Factory, Shanghai, China) to form a uniform thin film.…”

Section: Preparation Of Amb/mpp Micellesmentioning

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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Section: Preparation Of Amb/mpp Micellesmentioning

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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“…Similar results from Tang et al [51] indicate increased fungicidal activity of amphotericin B after incorporation into polymeric nanoparticles. It was also shown that encapsulation of amphotericin B poly(L-lactide) (PLA) nanoparticles reduces hemolytic activity of the drug without affecting its antifungal properties [10]. Moreover, a study from 2013 reported that amphotericin B-encapsulated PLGA-DMSA (poly[lactic-co-glycolic] acid and dimercaptosuccinic acid) nanoparticles might be an effective delivery system for the treatment of cutaneous leishmaniasis [52].…”

Section: Recent Advances In Application Of Antibioticconjugated Nanopmentioning

confidence: 99%

“…Specifically, nanosystems offer antibiotic delivery to the site of infection and extension of its action due to controlled release [7]. Additionally, the use of nanotechnology provides important improvements in the pharmacokinetics of antibiotics whose application is limited due to low solubility, poor bioavailability after oral administration, short half-life, high toxicity or instability in physiological conditions ( Figure 1) [8][9][10]. A broad spectrum of antimicrobial activity described for a variety of nanomaterials supports the idea that the employment of antibiotic-conjugated nanoformulations will provide a more efficient way to overcome the ever-growing drug resistance of pathogens [11,12].…”

Section: Introductionmentioning

confidence: 99%

Polymeric nanoparticles – a novel solution for delivery of antimicrobial agents

Michalak¹,

Głuszek²,

Piktel³

et al. 2016

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The increased prevalence of antibiotic-resistant pathogens requires additional efforts to develop new antimicrobial agents and alternative methods to prevent and treat infections. In response to this challenge, a variety of nanotechnology-based tools are currently being designed and thoroughly investigated. To date, a considerable number of studies have reported increased activity of antibiotic-conjugated polymeric nanoparticles against bacteria and fungi associated with various infections, including those caused by drug-resistant pathogens. Importantly, high biocompatibility of these structures coupled with enhanced biological activity and improved pharmacokinetic properties supports the potential of these nanosystems as new tools to treat infections. In this review, we summarize the synthesis of polymer-based nanoparticles and describe their mechanism of action. We also highlight the recent advances in the application of antibiotic-conjugated polymeric nanoparticles as novel antimicrobial agents. StreszczenieStale narastająca lekooporność drobnoustrojów wymusza konieczność rozwoju alternatywnych metod profilaktyki i terapii zakażeń, a także uzasadnia prace nad nowymi lekami o aktywności przeciwdrobnoustrojowej. Realizacja tego celu jest moż-liwa dzięki zastosowaniu osiągnięć z zakresu nanotechnologii. Zwiększająca się liczba doniesień literaturowych potwierdza znaczną aktywność przeciwdrobnoustrojową nanocząstek polimerowych skoniugowanych z klasycznymi antybiotykami, co może zostać wykorzystane w terapii infekcji o charakterze bakteryjnym i grzybiczym, również tych wywoływanych przez patogeny lekooporne. Wysoka biokompatybilność nanocząstek polimerowych, a także możliwość zwiększania aktywności przeciwdrobnoustrojowej i poprawy parametrów farmakokinetycznych stosowanych obecnie chemioterapeutyków, wskazuje na możliwość zastosowania nanostruktur w nowoczesnej terapii chorób infekcyjnych. W niniejszej pracy podsumowano metody syntezy nanosystemów opartych na nanocząstkach polimerowych, a także opisano mechanizm ich działania. Przedstawione zostały również najnowsze osiągnięcia w syntezie nanocząstek skoniugowanych z antybiotykami, pozwalające na ich zastosowanie w terapii infekcji o charakterze bakteryjnym i grzybiczym.

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“…The samples were analyzed by HPLC (Waters 2695 Alliance HPLC system, Milford, MA). The mobile phase consisted of acetonitrile, methanol and water mixture (40:50:10, v/v/v) at a flow rate of 1 mL/min, in an isocratic mode 28 . The injection volume was 20 mL and photodiode array detector was operated at 408 nm.…”

Section: Determination Of Amb Encapsulation Efficiencymentioning

confidence: 99%

Amphotericin B-loaded polymeric nanoparticles: formulation optimization by factorial design

Khalil

Mainardes

2014

Pharmaceutical Development and Technology

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In this study, PLGA or PLGA-PEG blend nanoparticles were developed loading amphotericin B (AmB), an antifungal agent broadly used in therapy. A 2(2) × 3(1) factorial experimental design was conducted to indicate an optimal formulation of nanoparticles containing AmB and demonstrate the influence of the interactions of components on the mean particle size and drug encapsulation efficiency. The independent variables analyzed were polymer amount (two levels) and organic phase (three factors in one level). The parameters methanol as cosolvent and higher polymer amount originated from the higher AmB encapsulation, but with the larger particle size. The selected optimized parameters were set as the lower polymer amount and ethyl acetate as cosolvent in organic phase, for both PLGA and PLGA-PEG nanoparticles. These parameters originated from nanoparticles with the size of 189.5 ± 90 nm and 169 ± 6.9 nm and AmB encapsulation efficiency of 94.0 ± 1.3% and 92.8 ± 2.9% for PLGA and PLGA-PEG nanoparticles, respectively. Additionally, these formulations showed a narrow size distribution indicating homogeneity in the particle size. PLGA and PLGA-PEG nanoparticles are potential carrier for AmB delivery and the factorial design presented an important tool in optimizing nanoparticles formulations.

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Poly(L-lactide) Nanoparticles Reduce Amphotericin B Cytotoxicity and Maintain Its <I>In Vitro</I> Antifungal Activity

Cited by 35 publications

References 0 publications

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

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

Polymeric nanoparticles – a novel solution for delivery of antimicrobial agents

Amphotericin B-loaded polymeric nanoparticles: formulation optimization by factorial design

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