Biodegradable nanoparticles for drug and gene delivery to cells and tissue

doi:10.1016/S0169-409X(02)00228-4

Advanced Drug Delivery Reviews

Volume 55, Issue 3, 24 February 2003, Pages 329-347

https://doi.org/10.1016/S0169-409X(02)00228-4 Get rights and content

Abstract

Biodegradable nanoparticles formulated from poly (d,l-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted/localized delivery of different agents including plasmid DNA, proteins and peptides and low molecular weight compounds. Research about the mechanism of intracellular uptake of nanoparticles, their trafficking and sorting into different intracellular compartments, and the mechanism of enhanced therapeutic efficacy of nanoparticle-encapsulated agent at cellular level is more recent and is the primary focus of the review. Recent studies in our laboratory demonstrated rapid escape of PLGA nanoparticles from the endo-lysosomal compartment into cytosol following their uptake. Based on the above mechanism, various potential applications of nanoparticles for delivery of therapeutic agents to the cells and tissue are discussed.

Section snippets

Significance of nanotechnology for drug therapy

In recent years, significant effort has been devoted to develop nanotechnology for drug delivery since it offers a suitable means of delivering small molecular weight drugs, as well as macromolecules such as proteins, peptides or genes by either localized or targeted delivery to the tissue of interest [1]. Nanotechnology focuses on formulating therapeutic agents in biocompatible nanocomposites such as nanoparticles, nanocapsules, micellar systems, and conjugates. Since these systems are often

Nanoparticles

Nanoparticles are submicron-sized polymeric colloidal particles with a therapeutic agent of interest encapsulated within their polymeric matrix or adsorbed or conjugated onto the surface [10]. We have been investigating nanoparticles formulated using a FDA approved biodegradable and biocompatible polymers, poly (d,l-lactide-co-glycolide) (PLGA) with a therapeutic agent encapsulated into the polymer for localized and sustained drug and macromolecular delivery (Fig. 1) [11], [12], [13], [14], [15]

Tissue targeting

Targeted delivery of therapeutic agents to specific tissues has been made feasible due to a number of developments such as monoclonal antibodies, discovery of specific receptors that are either over-expressed or expressed only in specific tissues, and development of conjugation techniques to attach antibodies or ligands to drug delivery systems. Targeted delivery results in higher bioavailability of the therapeutic agent at its site of action and at the same time results in reduced side

Future prospects

Results from our studies and those of others indicate that nanoparticles are a potentially useful drug delivery system capable of delivering a multitude of therapeutic agents by targeted and/or sustained delivery. Issues in drug delivery are becoming more important as more potent and specific drugs become available with the knowledge about diseases available from the human genome project. All therapeutic agents would optimally require drug delivery and targeting mechanisms to deliver them to

Acknowledgements

JP is supported by a Predoctoral Fellowship from American Heart Association, the Heartland Affiliate. The work described in the review is partially contributed by Dr. Wenzong Zhou, Swayam Prabha, Jasmine Davda, and Dr. Sanjeeb K. Sahoo in Dr. Labhasetwar’s laboratory. Some of the work described in the review was carried out in collaboration with Dr. Robert J. Levy, University of Pennsylvania, Philadelphia and Dr. Gordon L. Amidon, University of Michigan, Ann Arbor. Grant support from the

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Biodegradable nanoparticles for drug and gene delivery to cells and tissue

Abstract

Section snippets

Significance of nanotechnology for drug therapy

Nanoparticles

Tissue targeting

Future prospects

Acknowledgements

J. Control. Release

J. Pharm. Sci.

J. Control. Release

J. Control. Release

Adv. Drug Deliv. Rev.

Adv. Drug Deliv. Rev.

J. Control. Release

J. Pharm. Sci.

Colloids Surfaces B: Biointerfaces

J. Control. Release

J. Control. Release

Biomaterials

Adv. Drug Del. Rev.

J. Control. Release

Biochem. Biophys. Res. Comm.

Adv. Drug Del. Rev.

Cancer Treat. Rev.

Int. J. Pharm.

J. Biol. Chem.

J. Pharm. Sci.

Int. J. Pharm.

Adv. Drug Del. Rev.

J. Control. Release

J. Pharm. Sci.

J. Pharm. Sci.

Adv. Drug Deliv. Rev.

Adv. Enzyme Regul.

Adv. Drug Deliv. Rev.

Trends Pharmacol. Sci.

Am. Heart J.

J. Am. Coll. Cardiol.

J. Vasc. Interv. Radiol.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Long-circulating and target specific nanoparticles: theory to practice

Pharmacol. Rev.

Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells

Adv. Drug Del. Rev.

Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches

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Pharm. News

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