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Antifungal Agents01:15

Antifungal Agents

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Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
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Optimizing growth media enhances microbial proliferation and maximizes product yield. Statistical experimental design methodologies provide structured and reproducible approaches, offering progressively higher levels of robustness and efficiency.The One-Factor-at-a-Time (OFAT) MethodThe One-Factor-at-a-Time (OFAT) method involves adjusting a single variable while keeping all others constant. However, it cannot detect interactions between variables, often leading to suboptimal outcomes when...
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Site-Targeted Drug Delivery Systems: Polymeric Carriers

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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Biopharmaceutical Factors Influencing Drug Product Design: Overview01:22

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Rational drug product design integrates knowledge of the drug’s physicochemical properties, formulation components, manufacturing techniques, and intended route of administration. Each factor influences the drug’s performance, including how it is released, absorbed, and eliminated in the body.The physicochemical properties of a drug—such as solubility, stability, and particle size—affect its compatibility with excipients and the choice of dosage form. Excipients, though...
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Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
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PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure...
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Amphotericin B-loaded polymeric nanoparticles: formulation optimization by factorial design.

Talita Cristina Moreira Moraes Carraro1, Najeh Maissar Khalil1, Rubiana Mara Mainardes1

  • 1a Department of Pharmacy , Universidade Estadual do Centro-Oeste , Guarapuava , PR , Brazil.

Pharmaceutical Development and Technology
|November 12, 2014
PubMed
Summary

This study optimized poly(lactic-co-glycolic acid) (PLGA) and PLGA-PEG nanoparticles for delivering amphotericin B (AmB). A factorial design identified optimal parameters for high drug encapsulation and small particle size, crucial for effective antifungal therapy.

Keywords:
Antifungalencapsulation efficiencynanoencapsulationparticle sizepolydispersity index

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Area of Science:

  • Materials Science
  • Nanotechnology
  • Pharmaceutical Sciences

Background:

  • Amphotericin B (AmB) is a vital antifungal agent, but its use is limited by toxicity and poor solubility.
  • Nanoparticle drug delivery systems offer a promising strategy to improve AmB's therapeutic index.
  • Poly(lactic-co-glycolic acid) (PLGA) and its blend with polyethylene glycol (PLGA-PEG) are biocompatible polymers frequently used for nanoparticle formulation.

Purpose of the Study:

  • To develop and optimize PLGA and PLGA-PEG nanoparticles for encapsulating amphotericin B (AmB).
  • To investigate the influence of formulation parameters, specifically polymer amount and organic phase composition, on nanoparticle characteristics.
  • To determine the optimal formulation yielding high AmB encapsulation efficiency and desirable particle size for effective drug delivery.

Main Methods:

  • A 2(2)×3(1) factorial experimental design was employed to systematically study the effects of independent variables.
  • Independent variables included polymer amount (two levels) and organic phase composition (three factors).
  • Nanoparticle characterization involved measuring mean particle size and drug (AmB) encapsulation efficiency.

Main Results:

  • Optimized formulations using a lower polymer amount and ethyl acetate as the cosolvent resulted in nanoparticles with sizes of 189.5 ± 90 nm (PLGA) and 169 ± 6.9 nm (PLGA-PEG).
  • High AmB encapsulation efficiencies of 94.0 ± 1.3% (PLGA) and 92.8 ± 2.9% (PLGA-PEG) were achieved.
  • The optimized nanoparticles exhibited narrow size distributions, indicating formulation homogeneity.

Conclusions:

  • PLGA and PLGA-PEG nanoparticles are effective carriers for amphotericin B delivery.
  • The factorial design approach proved valuable for optimizing nanoparticle formulations, balancing particle size and drug encapsulation.
  • These optimized AmB-loaded nanoparticles hold potential for improved antifungal therapy with reduced side effects.