Nano-sized molecules in drug delivery

A new drug delivery method using nano-sized molecules to carry the chemotherapy drug doxorubicin to tumors improves the effectiveness of the drug in mice and increases their survival time, according to a study published online June 26 in the Journal of the National Cancer Institute.

.......Doxorubicin delivered by nanocarriers was more effective in preventing tumor growth than free doxorubicin, and the mice receiving this treatment method lived longer and had fewer toxic side effects.

"Encapsulation of doxorubicin...increased its accumulation and penetration in tumors in terms of both the percentage of cells that were reached by the drug and the intracellular levels that were attained," the authors write.

In an accompanying editorial, the future of drug delivery is discussed to be focused on three important research areas—drug combinations, targeting, and integration.

"The study by Tang [and colleagues] is a simple but effective demonstration of the benefits of integration of a drug with an appropriate carrier to yield a striking gain in efficacy," the authors write. "May the days of pharmacological missiles that miss their target and friendly fire that kills patients soon be over!"

Nanoparticles Carry Chemotherapy Drug Deeper into Solid Tumors; JNCI Journal of the National Cancer Institute 2007 99(13):981; doi:10.1093/jnci/djm068; jnci.oxfordjournals.org/cgi/content/full/99/13/981-c

Liposomes — microscopic phospholipid bubbles with a bilayered membrane structure — have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs — from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.

http://www.nature.com/nrd/journal/v4/n2/abs/nrd1632.html;
jsessionid=EDB42255B532A20B8DA12723DBB94B46



The utility of polymeric micelles formed through the multimolecular assembly of block copolymers as novel core–shell typed colloidal carriers for drug and gene targeting is highlighted. The process of micellization in aqueous milieu is described in detail based on differences in the driving force of core segregation, including hydrophobic interaction, electrostatic interaction, metal complexation, and hydrogen bonding of constituent block copolymers. The segregated core embedded in the hydrophilic palisade is shown to function as a reservoir for genes, enzymes, and a variety of drugs with diverse characteristics. Functionalization of the outer surface of the polymeric micelle to modify its physicochemical and biological properties is reviewed from the standpoint of designing micellar carrier systems for receptor-mediated drug delivery. Further, the distribution of polymeric micelles is described to demonstrate their long-circulating characteristics and significant tumor accumulation, emphasizing their promising utility in tumor-targeting therapy. As an important perspective on carrier systems based on polymeric micelles, their feasibility as non-viral gene vectors is also summarized in this review article.


Block copolymer micelles for drug delivery: design, characterization and biological significance; http://www.sciencedirect.com/


Polymeric micelles are nanoscopic core/shell structures formed by amphiphilic block copolymers. Both the inherent and modifiable properties of polymeric micelles make them particularly well suited for drug delivery purposes.......Relevant properties discussed include micellar association, morphology, size and stability. These properties and characterization techniques are included to provide context for the known advantages and applications of polymeric micelles for drug delivery. The advantages and applications discussed include solubilization of poorly soluble molecules, sustained release and size advantages, and protection of encapsulated substances from degradation and metabolism. The three most widely studied block copolymer classes are characterized by their hydrophobic blocks, and are poly(propylene oxide), poly(L-amino acid)s and poly(ester)s. These three classes of block copolymers are reviewed with multiple examples of current research in which formulation techniques with polymeric micelles have been applied to some of the most challenging molecules in the pharmaceutical industry. The polymeric micelles used for drug delivery in these examples have shown the abilities to attenuate toxicities, enhance delivery to desired biological sites and improve the therapeutic efficacy of active pharmaceutical ingredients.

Polymeric micelles for drug delivery;
http://www.ncbi.nlm.nih.gov/pubmed/17168771