Novel drug delivery systems is a field of which demands constant innovation. The healthcare industry is in continued search for delivery systems which can accurately deliver the drugs to target site with ideally no adverse effects. A poster-perfect drug delivery system is biocompatible and able deliver the active molecule at a constant rate, at the right dose, to the right site with no complications. Hence, the search for an idea drug carrier incorporates aspects of pharmacokinetics, pharmacodynamics, toxicological and immunological reactions, biorecognition and local biochemical interactions. In recent years, research in biochemical carriers for drug delivery has gained traction since these molecules can be adapted to meet most of the requirements of an ideal carrier and thus can be referred to as “smart” carriers. This includes liposomes, vectors, peptide drug adducts, dendrimers, micelles, microcapsules etc.
Molecular self-assembly can be defined as “spontaneous association of numerous individual entities into coherent organisation and well defined structures to maximize the benefit of the individual without external instruction”. The basic principle involves designing the molecules so that they interact and form numerous non-covalent bonds like hydrogen bonds, ionic bonds, Van der Waal’s interactions, etc leading to the formation of a stable structure into which a drug molecules can be incorporated. Peptides undergo self-assembly in nature leading to the formation of various peptide motifs like the α-helix and β- sheets.
Peptides can be engineered specifically with these motifs which then interact to form various supramolecular assemblies including nanovesicles, nanotubes, nanofibers, nanoribbons and hydrogels which can be used for drug delivery and immunological applications. Widely explored biomedical applications for self-assembling peptides include formation of scaffolds for tissue engineering and drug and vaccine delivery.
Self-assembling peptide molecules are biocompatible and can act as intracellular transporters due to high permeability through bio membranes with high drug loading capacity and low drug leakage. They encapsulate hydrophobic drug molecules through interactions with amino acid side chains. Stability against enzymatic degradation can be conferred to the drug molecules and sustained release profiles can also be achieved. This can be done by designing the drug to respond to specific stimuli like pH, temperature or enzymes. In addition to acting as a carrier, peptide itself can have some therapeutic value. These peptides also demonstrate a sequence and structure specific impacts of the immune system which can be switched off for drug delivery and switched on for vaccine delivery. Targeted delivery can be achieved by including adhesin ligands, receptor specific ligands or peptide based antigens in the peptide design.
Dalargin is a low bioavailability drug which acts on the µ receptors and is effluxed and metabolized in the blood. This problem can be overcome by using a amphiphilic dalargin derivative where a palmitoyl moiety has been attached to the hydroxyl residue on tyrosine via an ester bond and then self-assembled into β-sheets fibrils on sonication. These nanofibrils show improved stability in blood and increased bioavailability in the CNS.
Sequences of poly-aspartic acid have shown increased binding to hydroxyapatite which can effectively deliver small drug molecules to the bones. This can be effectively used to treat osteoporosis or osteosarcoma where the complex mineralisation can be a barrier for conventional drug delivery techniques.
Active or passive targeting using self-assembling peptides for chemotherapeutic agents in an arena of much exploration. The RGD sequence in the peptide amphiphile has cell adhesion property and can mimic the extracellular matrix specifically binding to the transmembrane glycoproteins during tumour growth and metastasis, thus successfully entering the cell. This can prove to be a promising carrier for cytotoxic material into cancerous cells.
The examples stated above clearly demonstrate the potential of self-assembling peptides to target various physiological systems with minimal incompatibilities. With more concentrated research in the area, peptide therapeutics can boost the efficiency of drug therapy tremendously.
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