BioTherapi: Bioinformatics for Therapeutic Peptides and Proteins

Peptide delivery Methods

Efficient delivery of peptide drugs to the desired site is very important. There are a number of barriers that may limit using peptides as potential drugs, some of these obstacles include poor biomembrane permeability, enzymatic degradation and low pH. To improve peptide drug efficiency a selective drug delivery system is required.

1. Polysaccharides/liposaccharides: Polysaccharides have been used for delivering drugs to colon. The rationale for using polysaccharides as a delivery system for colon is the presence of a number of polysaccharidases which biodegrade the carrier and release the drug. eg. chitosan, pectin, cyclodextrin, dextrans.
One polymer that received a lot of attention was chitin. The acetylation of chitin, which can be isolated from insects, crustacea such as crab and shrimp and some fungi leads to poly (β 1– 4 D-glucosamine) or so called chitosan. Chitosan displayed an improved paracellular route of absorption for peptide drugs. Use of liposaccharides to increase the lipophilicity of peptides, thereby increasing their membrane permeability.

2. Lipopeptides: In the early 1970s it was shown that conjugating fatty acids to bovine serum albumin changed the immune response from humoral response to a mainly delayed type hypersensitivity response. Lowell et al.complexed lipopeptides containing malaria epitopes to meningococcal outer membrane protein vesicles and induced high antibody levels against plasmodium falciparum sporozoites. Fatty acid addition to peptides can enhance bioavailability and membrane permeability of peptides that are poorly absorbed.

3. Liposomes: The popularity of liposomes as drug carriers partly arise from their biodegradability and the possibility of manipulating their structure to induce specificity and cell targeting. Liposomes have been used as a vehicle for delivering enzymes to defective cells where a specific enzyme deficiency exists. Peptides coupled to liposomes usually yield heterogeneous products and products that are ill defined both chemically and physically. To eliminate this problem, Gyongyossy-Issa et al. reported the use of disulfide linkage to the surface of intact liposome to attach a peptide representing one-half of a ligand-receptor pair. In this study an RGD-motif-containing peptide was coupled to the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine-N-[3-(2-pyridyldithio)propionate] (PDP-DOPE) of the liposomes by a thiol-disulfide exchange to achieve target specificity.

4. Polyethylene glycol (PEG): Many peptides and proteins have been conjugated with PEG to increase their circulation half life by greater than 50-fold. For example, degradable polymer microspheres containing Luteinizing Hormone Releasing Hormone (LHRH) have been used to maintain high systemic levels of this hormone.

5. Peptide carriers:Yamazaki et al. [23] investigated bioadhesive peptides that are fragments of adhesive proteins such as fibronectin and laminin, to deliver antitumor agents to specific cells.

Another promising method for delivering peptides was to incorporate the sequence of the peptide into the structure of a natural transport protein. In a study by Ali et al.human serum transferin (HST) was used as a the carrier protein and it contained the sequence of a peptide substrate of HIV-1 protease (VSQNYPIVL).