Drug Delivery Technology

M IMETIC DELIVERY S

YSTEMS

Mimetic Drug Delivery Systems for Release With

Specific Molecular Triggers

By: Lisa Brannon-Peppas, PhD

ABSTRACT

Although the field of controlled delivery in pharmaceutical and consumer products has grown exponentially throughout the past decade, most classical controlled-release systems provide only passive release. Some may release due to a change in temperature, and some may rupture due to applied pressure, but few if any can actually respond to the presence of one specific molecule in its environment and release its contents in response to that molecule and that molecule alone. The unique use of molecular imprinting in the Affinimer ^TMdelivery systems allows that sensitivity to become reality.

INTRODUCTION

Drug Delivery Technology June 2009 Vol 9 No 6

Recognition in nature is a complex orchestration of numerous interactions between individual atoms and cumulative interactions between secondary structures. For example, the active sites of enzymes are composed of several amino acid residues, which covalently bind ligand molecules in a very specific manner. However, the activity of the site is dependent on the stabilization of the three-dimensional structure by the interactions of hundreds of other residues within the structure of secondary and tertiary domains. The term configurational biomimesis refers to the three-dimensional arrangement of chemical groups that can specifically bind a biomolecule via non-covalent forces. This designed recognition involves analyzing the molecular basis of recognition in biological systems and attempts to mimic similar interactions on a molecular level. Molecularly imprinted polymers (MIPs) are polymers that are formed in the presence of an imprinted compound or

targeting chemical, biological, or other molecule such that the imprinted compound may later be removed, leaving an MIP that is able to recognize and bind to the imprinted compound via a binding cavity, perhaps even able to differentiate with isomeric specificity.^1-5

The design of a precise macromolecular chemical architecture that can recognize target molecules from an ensemble of closely related molecules has a large number of potential applications. The main thrust of research in this field has included separation processes (chromatography, capillary electrophoresis, solid-phase extraction, membrane separations), immunoassays and antibody mimics, biosensor recognition elements, and catalysis and artificial enzymes. However, relatively little attention has been paid to controlled delivery. ^6-11

Configurational biomimesis and nanoimprinting create stereo-specific three-dimensional binding cavities based on the template of interest. Configurational biomimetic imprinting techniques involve forming a pre-

polymerization complex between the template molecule and functional monomers or functional oligomers (or polymers) with specific chemical structures designed to interact with the template either by covalent, non-covalent chemistry (self-assembly) or both (Figure 1).

Proper tuning of non-covalent interactions, such as increasing macromolecular chain hydrophobicity, including strong ionic directed recognition sites with hydrophobic domains, or including stronger hydrogen bond donors and acceptors, has been shown to enhance binding and achieve selective recognition in aqueous solutions. Thermodynamic analysis regarding energy contributions of ligand-receptor binding outlines the importance of directed tuning of these parameters in non-covalent recognition.