3. Artificial "cell" for targeted delivery of pharmaceutical agents.

 

The past half century has witnessed extraordinary advances in molecular biology and biochemical engineering to develop vast arrays of therapeutic agents. The development of delivery strategies to efficiently implement these agents is equally important but has lagged behind. Although it is possible to surgically input biodegradable drug-loaded implants [1], intravenous administration provides the most versatile accessibility. Two major challenges exist: 1. Specific targeting [2,3]. The drugs ought to be delivered to the right location and released in the right time frame; 2. Biological barriers [4]. The drugs ought to overcome biological barriers and reach their targeting sites in significant numbers. These challenges are especially urgent for the delivery of anti-cancer drugs due to their narrow therapeutic index and often challenging physical characteristics. Most of anti-cancer drugs in clinical use today are delivered with poor tumor specificity, which leads to high systemic toxicity. Currently approaches under development oftentimes involve a 1:1 conjugation or chemical bonding of an anti-cancer drug to a “helper” carrier [5-7]. Besides their problematic conversion yield and potential adverse effect to the functions of the drug, the circulation, uptake and release profile of the drugs could be altered significantly to induce undesired complications.

artificial cell

 

Development of biologically-benign carriers to efficiently deliver drug payloads has long been pursued. Liposome is one of the most widely studied vesicles, and a number of intravenously administered liposome-based drug formulations have already been licensed to the market [8,9]. Its success is attributed to the innocuous nature of many liposomal components and the structural versatility of the system [9]. For example, antibodies or ligands can be attached to the exterior surface of liposomes for site-specific targeting [3,10], and liposomes containing lipid derivatives of polyethylene glycol (PEG) have significantly prolonged circulation time to allow efficient extravagation to the targeted sites [8,9]. One outstanding problem for liposome-based delivery is the difficulty to encapsulate insoluble therapeutic agents. Unfortunately, nearly 70% of drugs coming from early pre-clinical development have low solubility [11], and most of anti-cancer drugs in the market are fairly hydrophobic [12,13].

 

Nanotechnology is expected to play a pivotal role for drug delivery in the postgenomic era [14], partly because the nanoscopic size allows the drug carriers to break the biological barriers more easily and interact with the nanostructured biological assemblies directly. However, when these inherently nonselective carriers enter the circulation, the general opsonization-mediated phagocytosis, cytotoxicity and immunogenicity are the intrinsic problems [14].

 

One of the ideal platforms for next generation drug delivery could be a hybrid system that combines the versatile liposome systems with emerging nanotechnologies. We are working to design and create hybrid artificial “cells” that can be used as delivery vesicles. The “cells” consist of a bioactive membrane to encapsulate a functional “nucleus”. The membrane helps the “nucleus” navigate to the desired sites before being engulfed by the immune system, and the “nucleus” either bears therapeutic function itself, or acts as a universal carrier for payloads.

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[14] Ferrari, M. Cancer nanotechnology: Opportunities and challenges. Nature Reviews Cancer 2005, 5, 161-171