Self-aggregated nanoparticles based on amphiphilic poly(lactic acid)-grafted-chitosan copolymer for ocular delivery of amphotericin B

Zhou, Wenjun; Wang, Yuanyuan; Jian, Jiuying; Song, Shengfang

doi:10.2147/ijn.s51186

Cited by 34 publications

(13 citation statements)

References 41 publications

(51 reference statements)

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“…AmB was loaded into MPPI dendrimers by using an equilibrium dialysis method following the reported procedure (10,18), with slight modifications. The release kinetics of AmB was determined in two different release media: phosphate-buffered saline (PBS), pH 7.4, and sodium acetate buffer, pH 5.5, each containing 1% (vol/vol) Tween 80 (19,20). The amount of drug released was determined by high-pressure liquid chromatography (HPLC), using acetonitrile-acetic acid (10%)-water (41:43:16) as the mobile phase, a flow rate of 1.2 ml/min, a UV detector at 405 nm, and a C 18 column (4 mm ϫ 150-mm inner diameter) (21,22).…”

Section: Methodsmentioning

confidence: 99%

Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

Jain

Verma

Mishra

et al. 2015

Antimicrob Agents Chemother

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The present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR), 1 H nuclear magnetic resonance ( 1 H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency, in vitro drug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellular Leishmania donovani amastigotes, in vivo pharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pHsensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagic L. donovani amastigotes. In the in vitro cell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs. In vivo studies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity. Nanomedicine has immense potential in drug delivery because of nanoscale size-derived chemical, physical, and biological properties. Dendritic polymers, including dendrigrafts, dendrimers, and dendrons, are providing new directions in nanomaterialbased drug delivery due to their nanostructure, monodispersity, versatility, well-defined molecular size, tailor-made surface groups, and chemical stability. The unique physicochemical and biological properties of dendrimers are due to their stepwise controlled synthesis, which is accomplished by sequential addition of layers/generations surrounding the core (1-4).Scientists are continuously investigating approaches for targeted delivery of antiparasitic drugs to macrophages because parasites reside and multiply within host macrophages in infectious diseases such as salmonellosis, leishmaniasis, histoplasmosis, listeriosis, cryptococcosis, candidiasis, AIDS, etc. Targeted delivery to macrophages in cases of infectious disease is expected to improve the therapeutic index by...

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Section: Methodsmentioning

confidence: 99%

Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

Jain

Verma

Mishra

et al. 2015

Antimicrob Agents Chemother

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“…When assessing in vitro drug release of a hydrophobic drug, sink conditions were maintained. These conditions were maintained by inclusion of 1% (v/v) Tween in the phosphate buffer [17,19]. This allowed the total quantity of drug can be eluted from the nanocarriers and to reduce the adhesion of AmB onto the dialyzing membrane wall.…”

Section: Resultsmentioning

confidence: 99%

Development of mannose-anchored Thiolated Amphotericin B Nanocarriers for Treatment of Visceral Leishmaniasis

Shahnaz

Edagwa

McMillan

et al. 2016

Nanomedicine (Lond.)

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Aim:Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized.Materials & methods:A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities.Results:MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug.Conclusion:These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

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“…An in vivo ocular pharmacokinetic study showed a prolonged precorneal retention time. Moreover, no sign of irritation was observed during the ocular irritation study [99]. Chitosan was also combined with PEG to formulate resveratrol-loaded NPs [100] and resveratrol and quercetin co-encapsulated…”

Section: Combination Of Natural and Synthetic Polymersmentioning

confidence: 99%

Advances and limitations of drug delivery systems formulated as eye drops

Jumelle

Gholizadeh

Annabi

et al. 2020

Journal of Controlled Release

199

125

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show abstract

Self-aggregated nanoparticles based on amphiphilic poly(lactic acid)-grafted-chitosan copolymer for ocular delivery of amphotericin B

Cited by 34 publications

References 41 publications

Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

Development of mannose-anchored Thiolated Amphotericin B Nanocarriers for Treatment of Visceral Leishmaniasis

Advances and limitations of drug delivery systems formulated as eye drops

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