Challenges associated with penetration of nanoparticles across cell and tissue barriers: A review of current status and future prospects

• Published in: Nano today Vol. 9; no. 2; pp. 223 - 243
• Main Authors: Barua, Sutapa, Mitragotri, Samir
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-04-2014; Elsevier
• Subjects: Applied sciences; Biological barriers; Cross-disciplinary physics: materials science; rheology; Delivery; Electronics; EPR; Exact sciences and technology; Materials science; Molecular electronics, nanoelectronics; Nanocrystalline materials; Nanomedicine; Nanoparticle; Nanoscale materials and structures: fabrication and characterization; Nanotubes; Physics; Quantum dots; Semiconductor electronics. Microelectronics. Optoelectronics. Solid state devices; Transport; Delivery; Transport; Nanoparticle; Nanomedicine; EPR; Biological barriers; Gold; Dendrimer; Pressure effects; Doses; Quantum dots; Aromatic polymer; Carbon nanotubes; Nanoparticles; Endocytosis; Reviews; Micelles; Diffusion; Polymers; Nanostructured materials; Nanomaterial synthesis
• ISSN: 1748-0132; 1878-044X
• DOI: 10.1016/j.nantod.2014.04.008

•Transport barriers for delivery of nanoparticles are discussed.•Permeation across the endothelium, diffusion in the interstitium and entry into cells is discussed.•Permeation of nanoparticles across the skin and mucosal membranes is discussed.
Nanoparticles (NPs) have emerged as an effective modality for the treatment of various diseases including cancer, cardiovascular and inflammatory diseases. Various forms of NPs including liposomes, polymer particles, micelles, dendrimers, quantum dots, gold NPs and carbon nanotubes have been synthesized and tested for therapeutic applications. One of the greatest challenges that limit the success of NPs is their ability to reach the therapeutic site at necessary doses while minimizing accumulation at undesired sites. The biodistribution of NPs is determined by body's biological barriers that manifest in several distinct ways. For intravascular delivery of NPs, the barrier manifests in the form of: (i) immune clearance in the liver and spleen, (ii) permeation across the endothelium into target tissues, (iii) penetration through the tissue interstitium, (iv) endocytosis in target cells, (v) diffusion through cytoplasm and (vi) eventually entry into the nucleus, if required. Certain applications of NPs also rely on delivery through alternate routes including skin and mucosal membranes of the nose, lungs, intestine and vagina. In these cases, the diffusive resistance of these tissues poses a significant barrier to delivery. This review focuses on the current understanding of penetration of NPs through biological barriers. Emphasis is placed on transport barriers and not immunological barriers. The review also discusses design strategies for overcoming the barrier properties.