Drug Delivery

17.04

Drug Delivery Platforms

A great majority of drugs fail to pass through clinical trials due to detrimental side effects or short plasma half lives, and drug nanocarrier systems have received considerable attention in the recent decade as target-specific vectors capable of avoiding such complications. The main focus of such approaches is to develop a nanocarrier system by which a therapeutic molecule can be delivered selectively to its target tissue or cell type, hence increasing drug efficacy, reducing effective doses and minimizing toxic effects compared to the administration of the vector-free drug. Our group studies a wide array of drug vectors, including peptide amphiphile nanofibers, nanospheres, liposomes and SPIONs (superparamagnetic iron oxide nanoparticles). We have previously demonstrated that a cationic peptide amphiphile (lauryl-VVAGK) could serve as an efficient vector for the delivery and slow release of therapeutic oligonucleotides, (Bulut, 2011) and are currently investigating different strategies for the enhacement of drug uptake and targeting capabilities in liposomes. In addition to conventional drugs, we are also working on the peptide amphiphile-mediated delivery of SPIONs, novel MRI contrast agents with low toxicity and considerable potential in theranostics, and have previously shown that SPION solubilities were improved following non-covalent functionalization by the peptide amphiphiles lauryl-VVAGK and lauryl-VVAAD (Sulek, 2011).

Peptide-based Antigens and Adjuvants

Vaccines and adjuvants play important roles in the defense of the body against complex diseases such as cancer and intracellular pathogens such as malaria and hepatitis C. The ability of a vaccine to stimulate the immune system can be increased through the use of adjuvants, which elicit the humoral immune response without affecting cellular immunity. A strong CD8T cell response is desirable for long-term protection against infectious agents, and advanced methods such as recombinant DNA technologies and nanotechnology can be used to further bolster the efficiency of a prospective vaccine. Synthetic vaccines and adjuvants in particular have attracted great interest for their potential to simultaneously promote the humoral and cellular immune responses against fast-acting pathogens. In our lab, we fabricate nanosphere- or nanofiber-forming peptide amphiphile molecules to replicate the morphology of common spherical and fusiform viruses and use them in conjunction with nucleotide drugs that are widely used as adjuvants for triggering Toll-like receptors. The presence of antigenic peptides and the nucleotide adjuvant in close proximity is expected to increase the efficiency of these nanostructures in inducing robust antigen-specific humoral and cellular immune response, in addition to enhancing their ability to deliver an exogenously provided antigen.

Selected publications:

Mumcuoglu D, Sardan M, Tekinay T, Guler MO, Tekinay AB. Oligonucleotide Delivery with Cell Surface Binding and Cell Penetrating Peptide Amphiphile Nanospheres, Mol Pharm. 2015; DOI: 10.1021/acs.molpharmaceut.5b00007

Bulut S, Erkal TS, Toksoz S, Tekinay AB, Tekinay T, Guler MO, Slow Release and Delivery of Antisense Oligonucleotide Drug by Self-Assembled Peptide Amphiphile Nanofibers, Biomacromolecules, 12(8): 3007–3014, 2011.