PLGA nanoparticles and nanosuspensions with amphotericin B: Potent in vitro and in vivo alternatives to Fungizone and AmBisome

Ven, H. Van de; Paulussen, Caroline; Feijens, Pim-Bart; Matheeussen, An; Rombaut, Patrick; Kayaert, Peter; Mooter, Guy Van den; Weyenberg, Wim; Cos, Paul; Maes, Louis; Ludwig, Annick

doi:10.1016/j.jconrel.2012.05.037

Cited by 140 publications

(79 citation statements)

References 51 publications

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“…In addition, pure Cs and ChS, as well as NQ and NQC nanoparticles presented no significant toxicity for macrophages. Van de Ven et al 60 and Corware et al 61 also obtained blank nanoparticles without significant cytotoxicity in macrophages, but when they were loaded with AmpB, the evaluated systems demonstrated an increase in their toxicity. Finally, hemolytic activity was also determined as a cytotoxicity parameter, and it was observed that none of the nanoparticle formulations resulted in significant hemolysis.…”

mentioning

confidence: 99%

Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system

Ribeiro

Chávez-Fumagalli

Valadares

et al. 2014

IJN

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The study reported here aimed to develop an optimized nanoparticle delivery system for amphotericin B (AmpB) using a polyelectrolyte complexation technique. For this, two oppositely charged polymers presenting anti-leishmanial activity – chitosan (Cs) and chondroitin sulfate (ChS) – were used: Cs as a positively charged polymer and ChS as a negatively charged polymer. The chitosan (NQ) nanoparticles, chitosan-chondroitin sulfate (NQC) nanoparticles, and chitosan-chondroitin sulfate-amphotericin B (NQC-AmpB) nanoparticles presented a mean particle size of 79, 104, and 136 nm, respectively; and a polydispersity index of 0.2. The measured zeta potential of the nanoparticles indicated a positive charge in their surface, while scanning and transmission electron microscopy revealed spherical nanoparticles with a smooth surface. Attenuated total reflectance-Fourier transform infrared spectroscopy analysis showed an electrostatic interaction between the polymers, whereas the release profile of AmpB from the NQC-AmpB nanoparticles showed a controlled release. In addition, the Cs; ChS; and NQ, NQC, and NQC-AmpB nanoparticles proved to be effective against promastigotes of Leishmania amazonensis and Leishmania chagasi , with a synergistic effect observed between Cs and ChS. Moreover, the applied NQ, NQC, and NQC-AmpB compounds demonstrated low toxicity in murine macrophages, as well as null hemolytic activity in type O + human red blood cells. Pure AmpB demonstrated high toxicity in the macrophages. The results show that cells infected with L. amazonensis and later treated with Cs, ChS, NQ, NQC, NQC-AmpB nanoparticles, or pure AmpB presented with a significant reduction in parasite number in the order of 24%, 31%, 55%, 66%, 90%, and 89%, respectively. The data presented indicate that the engineered NQC-AmpB nanoparticles could potentially be used as an alternative therapy to treat leishmaniasis, mainly due its low toxicity to mammals’ cells.

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confidence: 99%

Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system

Ribeiro

Chávez-Fumagalli

Valadares

et al. 2014

IJN

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“…However, this reduces the tissue fungal burden by no more than 30% as compared with controls, indicating limited in vivo efficacy of these formulations. [5][6][7] In addition, the stability, tissue permeability, degradation rate, and toxicity of NPs themselves are also concerns in this field. [8][9][10] The recently developed diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA) [hereafter, referred to as PLGA-TPGS]) has received special attention as a promising antimicrobial agent, due to its good biocompatibility and biodegradability.…”

mentioning

confidence: 99%

“…[8][9][10] The recently developed diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA) [hereafter, referred to as PLGA-TPGS]) has received special attention as a promising antimicrobial agent, due to its good biocompatibility and biodegradability. 7 Therefore, the synthesis of uniform PLGA-TPGS copolymer NPs (PLGA-TPGS NPs) with specific requirements in terms of size, shape, and physical and chemical properties is of great interest in the development of new drugs. 8,9 A variety of studies [8][9][10] have shown they have good biocompatibility and biodegradability and excellent targeted drug delivery, but the antifungal effects of AMB-loaded PLGA-TPGS NPs (AMBNPs) are mostly unknown.…”

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confidence: 99%

Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA) nanoparticles in vitro and in vivo

Tang¹,

Zhu²,

Sun³

et al. 2014

IJN

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Background Amphotericin B (AMB) is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs) – diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (PLGA-TPGS) – have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs) and evaluate their antifungal effects in vitro and in vivo. Methods AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo. Results AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual minimum inhibitory concentration of AMB-NPs against Candida albicans was significantly lower than that of free AMB, and AMB-NPs were less toxic on blood cells. In vivo experiments indicated that AMB-NPs achieved significantly better and prolonged antifungal effects when compared with free AMB. Conclusion The AMB-PLGA-TPGS NP system significantly improves the AMB bioavailability by improving its antifungal activities and reducing its toxicity, and thus, these NPs may become a good drug carrier for antifungal treatment.

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“…One nanoparticle formulation was more effective than AmBisome and, at the same time, less cytotoxic and hemotoxic. 97 Although very promising, especially as an antifungal agent, no further in vivo clinical applications have since been reported.…”

Section: Polymer Nanoparticlesmentioning

confidence: 99%

“…This phenomenon is not frequent in the case of AmpB, because in polymeric NP, only a small fraction of the drug is present in the free, monomeric form, the majority remaining superaggregated and associated with the delivery system. 97 The majority of nanostructures achieved interesting ranges of DL (up to 44% in one case). Passive or "natural" targeting, since the MPS cells are considered to be the main target for therapeutic interventions in leishmaniasis, is a mechanism that may be used to enhance drug concentration, reducing aspecific toxicity (hematotoxicity and kidney toxicity).…”

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confidence: 95%

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

Bruni¹,

Stella²,

Giraudo³

et al. 2017

IJN

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Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania , which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

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PLGA nanoparticles and nanosuspensions with amphotericin B: Potent in vitro and in vivo alternatives to Fungizone and AmBisome

Cited by 140 publications

References 51 publications

Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system

Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system

Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA) nanoparticles in vitro and in vivo

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

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