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Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats

and

Pharmaceutics 2011, 3(1), 1-11; https://doi.org/10.3390/pharmaceutics3010001 - 27 Dec 2010

Cited by 114 | Viewed by 10320

Abstract

We have reported that PEGylated liposomes lose their long-circulating properties when they are administered repeatedly at certain intervals to the same animal. This unexpected phenomenon is referred to as the accelerated blood clearance (ABC) phenomenon. We recently showed that the ABC phenomenon is triggered via the abundant secretion of anti-PEG IgM in response to the first dose of PEGylated liposomes. However, the details of the underlying mechanism for the induction of anti-PEG IgM production are yet to be elucidated. The present study demonstrated that the spleen is a major organ involved in the secretion of anti-PEG IgM in mice and rats. Anti-PEG IgM production was detected in nude, T-cell deficient mice, but not in SCID mice with B- and T-cell deficiencies. These observations indicate that splenic B-cells secret anti-PEG IgM without help from T-cells. Sequential injections of PEGylated liposomes into the same mice did not promote isotype switching from IgM to IgG. Accordingly, PEGylated liposomes may function as a type-2, T-cell-independent antigen (TI-2 antigen) during anti-PEG IgM production. Although the underlying mechanism that causes an anti-PEG IgM response against PEGylated liposomes is not yet clear, our findings give implications in revealing the anti-PEG IgM response against PEGylated liposome. Full article

(This article belongs to the Special Issue Nanotechnology in Drug Delivery)

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Nanotechnology and Drug Delivery: An Update in Oncology

Tait Jones

and

Nabil Saba

Pharmaceutics 2011, 3(2), 171-185; https://doi.org/10.3390/pharmaceutics3020171 - 14 Apr 2011

Cited by 13 | Viewed by 8056

Abstract

The field of nanotechnology has exploded in recent years with diverse arrays of applications. Cancer therapeutics have recently seen benefit from nanotechnology with the approval of some early nanoscale drug delivery systems. A diversity of novel delivery systems are currently under investigation and an array of newly developed, customized particles have reached clinical application. Drug delivery systems have traditionally relied on passive targeting via increased vascular permeability of malignant tissue, known as the enhanced permeability and retention effect (EPR). More recently, there has been an increased use of active targeting by incorporating cell specific ligands such as monoclonal antibodies, lectins, and growth factor receptors. This customizable approach has raised the possibility of drug delivery systems capable of multiple, simultaneous functions, including applications in diagnostics, imaging, and therapy which is paving the way to improved early detection methods, more effective therapy, and better survivorship for cancer patients. Full article

(This article belongs to the Special Issue Nanotechnology in Drug Delivery)

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Open AccessReview

Nano Delivers Big: Designing Molecular Missiles for Cancer Therapeutics

by Sachin Patel, Ashwin A. Bhirde, James F. Rusling, Xiaoyuan Chen, J. Silvio Gutkind and

Vyomesh Patel

Pharmaceutics 2011, 3(1), 34-52; https://doi.org/10.3390/pharmaceutics3010034 - 13 Jan 2011

Cited by 41 | Viewed by 10954

Abstract

Current first-line treatments for most cancers feature a short-list of highly potent and often target-blind interventions, including chemotherapy, radiation, and surgical excision. These treatments wreak considerable havoc upon non-cancerous tissue and organs, resulting in deleterious and sometimes fatal side effects for the patient. In response, this past decade has witnessed the robust emergence of nanoparticles and, more relevantly, nanoparticle drug delivery systems (DDS), widely touted as the panacea of cancer therapeutics. While not a cure, nanoparticle DDS can successfully negotiate the clinical payoff between drug dosage and side effects by encompassing target-specific drug delivery strategies. The expanding library of nanoparticles includes lipoproteins, liposomes, dendrimers, polymers, metal and metal oxide nano-spheres and -rods, and carbon nanotubes, so do the modes of delivery. Importantly, however, the pharmaco-dynamics and –kinetics of these nano-complexes remain an urgent issue and a serious bottleneck in the transition from bench to bedside. This review addresses the rise of nanoparticle DDS platforms for cancer and explores concepts of gene/drug delivery and cytotoxicity in pre-clinical and clinical contexts. Full article

(This article belongs to the Special Issue Nanotechnology in Drug Delivery)

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