PHARMACEUTICAL NANOTECHNOLOGY
Zidovudine-loaded PLA and PLA–PEG blend nanoparticles: Influence of polymer type on phagocytic uptake by polymorphonuclear cells

https://doi.org/10.1002/jps.21406Get rights and content

Abstract

Mononuclear (macrophages) and polymorphonuclear leucocytes cells play an important role in the immunopathogenesis of acquired immunodeficiency syndrome. Zidovudine is a broad-spectrum drug used in current antiretroviral therapy. The development of controlled drug delivery systems for the treatment of chronic diseases is of great interest since these systems can act as vectors, carrying the drug only to the target, and the adverse effects can be reduced. In this study, PLA and PLA/PEG blend nanoparticles containing zidovudine were developed and their uptake by polymorphonuclear leucocytes were studied in vitro. The influence of polymer type on particle size, Zeta potential and particle uptake by polymorphonuclear leucocytes was investigated. The cells were isolated from rat peritoneal exudate and their activation by nanoparticles was measured by luminol-dependent chemiluminescence and microscopical analysis. The PEG in the blend modified the Zeta potential suggested the formation of a PEG coat on the particle surface. The phagocytosis depended on the PEG and its ratio in the blend, the results showed that the PLA nanoparticles were more efficiently phagocytosed than PLA/PEG blends. The blend with the highest PEG proportion did not prevent phagocytosis, indicating that the steric effect of PEG was concentration dependent. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:257–267, 2009

Section snippets

INTRODUCTION

Poly(lactide acid) (PLA) nanoparticles have been extensively used for the development of controlled drug-delivery systems. PLA nanoparticles, due to their physicochemical properties (size, surface charge, and hydrophobicity), are recognized by polymorphonuclear neutrophils or mononuclear cells, inducing phagocytosis,1,2 after intravenous administration. The neutrophils and mononuclear cells recognize pathogenic microorganisms and also may recognize polymeric surfaces as foreign material,3 and

Materials

The polymers studied were poly(lactide acid) (PLA) (Mw 40–100 kDa) (viscosity 0.15–0.25) from Sigma (St. Louis, MO) and poly(ethylene glycol) (PEG) (Mw 6 kDa). The surfactant used in the emulsification process was polyvinyl alcohol (PVA) (18 kDa—85% hydrolyzed) from Sigma. The organic solvent was methylene chloride (Labsynth Ltd., Diadema, Brazil). Zidovudine was a gift from FURP (Brazil). Distilled water of Milli-Q quality was used as the suspending medium. Luminol, trypan blue solution and

Nanoparticles Characterization

The double emulsion-solvent evaporation method was successful in producing nanoparticles containing AZT. This method is particularly interesting to encapsulate hydrophilic molecules. The results of AZT encapsulation efficiency can be observed in Table 1. It was observed that for a constant PLA concentration, the efficiency encapsulation of AZT on nanoparticles increases with increasing PEG concentration in blend. Modifying the surface characteristics of nanoparticles it is possible to obtain

DISCUSSION

The objective of this study was to analyze the importance of nanoparticlecharacteristics in inducing the oxidative burst of neutrophils monitored by chemiluminescence luminol-dependent. Another aim was to examine if nanoparticles composed of blends containing PEG could have steric properties, and if the PEG ratio could affect the extent of phagocytosis. For copolymers these effect is well characterized and established, but for blends (physical mixture of polymers) not yet, since the forces that

Acknowledgements

The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/Brazil for the financial support.

REFERENCES (30)

Cited by (90)

  • Nanoparticle-based strategies to target HIV-infected cells

    2022, Colloids and Surfaces B: Biointerfaces
  • PEGylated liposomes as an emerging therapeutic platform for oral nanomedicine in cancer therapy: in vitro and in vivo assessment

    2020, Journal of Molecular Liquids
    Citation Excerpt :

    High absolute value of zeta potential indicates a high electric charge on the surface of the drug-loaded liposomes which cause strong repellent forces among liposomal vesicles to prevent their aggregation during hydrated state [52]. So, highly electrostatically stabilized colloidal dispersion is expected to have high zeta potential of around ±30 mV to produce stable liposomes [53]. Therefore, prior to freeze-drying the physicochemical parameters of EXE-CON-LIPO and EXE-PEG-LIPO were analyzed.

  • Nanopharmaceuticals in immunology: What’s new in research?

    2018, Emerging Nanotechnologies in Immunology: The Design, Applications and Toxicology of Nanopharmaceuticals and Nanovaccines
View all citing articles on Scopus
View full text