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Journal ArticleDOI

Pegylated poly(lactide) and poly(lactide-co-glycolide) nanoparticles: preparation, properties and possible applications in drug delivery.

30 Sep 2004-Current Drug Delivery (Curr Drug Deliv)-Vol. 1, Iss: 4, pp 321-333
TL;DR: The ability of the PLA-Peg and PLGA-PEG nanoparticles to evade rapid phagocytocis has extended the range of sites within the body that the nanoparticles can reach, which has significant implications with regard to their application in controlled drug delivery and targeting.
Abstract: The preparation, properties and potential applications in drug delivery of biocompatible and biodegradable PLA-PEG and PLGA-PEG nanoparticles are discussed. PLA-PEG and PLGA-PEG nanoparticles have been produced by emulsification-solvent evaporation, solvent displacement and salting out methods. The nanoparticles can be stored as freeze-dried powders, but an adequate amount of a suitable lyoprotectant should be added prior lyophilisation to prevent nanoparticle aggregation and retain nanoparticle redispersibility. The nanoparticles have a core-shell structure with a PLA core and a PEG coating. Their basic colloidal properties and degradation depend on copolymer composition. The PLA-PEG and PLGA-PEG nanoparticles exhibit prolonged blood circulation following intravenous administration to animals. The composition of the nanoparticles determine their biodistribution properties, probably through its effects on the effectiveness of the PEG steric barrier and the size of the nanoparticles. The ability of the PLA-PEG and PLGA-PEG nanoparticles to evade rapid phagocytocis has extended the range of sites within the body that the nanoparticles can reach, which has significant implications with regard to their application in controlled drug delivery and targeting. The PLA-PEG and PLGA-PEG nanoparticles can be loaded with a variety of bioactive agents achieving satisfactory loading, especially in the case of hydrophobic drugs. The nanoparticles have been investigated for the treatment of infectious diseases and cancer, the intravenous and mucosal delivery of proteins, and oligonucleotide and gene delivery. The results have been encouraging and PLA-PEG and PLGA-PEG nanoparticle formulations, improving the therapeutic potential of both established and new drugs, may be expected to be available in the near future.
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Journal ArticleDOI
TL;DR: These factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation.
Abstract: Nanoparticle (NP) drug delivery systems (5−250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, de...

3,009 citations

Journal Article
TL;DR: In this article, the authors discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation, including interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and targeting ligand functionalization.
Abstract: Nanoparticle (NP) drug delivery systems (5−250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, de...

2,543 citations

Journal ArticleDOI
TL;DR: In this critical review, insights are provided into the design and development of targeted polymeric NPs and the challenges associated with the engineering of this novel class of therapeutics are highlighted, including considerations of NP design optimization, development and biophysicochemical properties.
Abstract: Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).

1,407 citations

Journal ArticleDOI
TL;DR: It is found that NP mean volumetric size correlates linearly with polymer concentration for NPs between 70 and 250 nm in diameter and the ability to control NP size together with targeted delivery may result in favorable biodistribution and development of clinically relevant targeted therapies.

1,248 citations


Cites background from "Pegylated poly(lactide) and poly(la..."

  • ...such as particle size, nature of the polymer and drug, and surface biochemical properties [6]....

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