Peptide-based drug delivery systems

Otvos, L., Jr., Cudic, M., Chua, B.Y., Deliyannis, G., and Jackson, D.C. (2004) An insect antibacterial peptide-based drug delivery system. Mol. Pharmaceut. 1, 220-232. 

C. Moon, Y. M. Kwon, W. K. Lee, Y. J. Park and V. C. Yang, In vitro assessment of a novel polyrotaxane-based drug delivery system integrated with a cell-penetrating peptide, /. Control. Release, 124,... 

A composition based on diketopiperazine derivatives (3,6-bis (N-fumaryl-N-(n-butyl) amino-2, 5-diketopiperazine) has been investigated as a pulmonary drug delivery system, termed Technospheres (Pharmaceutical Discovery Corp., Elmsford, NY) (Pohl et al. 2000 Steiner et al. 2002). The diketopiperazine derivatives self-assemble into microparticles at low pH with a mean diameter of approximately 2 pm. During self-assembly, diketopiperazine derivatives microencapsulate peptides present in the solution. Insulin incorporated in diketopiperazine derivatives (TI) was administered to five healthy humans by the use of a capsule-based inhaler with a passive powder deagglomeration mechanism. Relative and absolute bioavailability of TI in the first 3 hours (0-180 min) were 26 12% and 15 5%, and for 6 hours (0-360 min) 16 8% and 16 6%, respectively (Steiner et al. 2002). The time to peak action for glucose infusion rates was shorter with both IV (14 6 min) injection and inhalation (39 36 min), as compared to SC administration (163 25 min). This rapid absorption of insulin would be beneficial for diabetic patients who need to rapidly affect their glucose levels. 

Different drug delivery systems have been proposed for vaginal delivery of peptides and proteins. The first one was a mucoadhesive gel based on polyacrylic acid intended for vaginal administration of insulin [96]. More recently, microparticulate systems such as starch and hyaluronan ester (HYAFF) microspheres have been proposed for vaginal delivery of insulin... 

Clausen, A. E. and Bernkop-Schnurch, A. Development an in vitro evaluation of a peptide drug delivery system based on thiolated polycarbophil. Pharm. Ind. 2001 63, 312-... 

Progress in drug delivery systems and new proteins/ peptides being developed for parenteral administration has created a need to expand the list of excipients that can be safely used. An informational chapter included in the USP 24, presents a scientifically based approach for safety assessment of new pharmaceutical excipi-ents.f This chapter is based on the excipient safety evaluation guidelines prepared by The Safety Committee of the International Pharmaceutical Excipient Council, with appropriate reaction. Table 14 summarizes the approach in developing a new excipient. 

Self-assembled nanoparticulates comprise various kinds of polymeric, peptide-based, and lipoidal systems. The rationale for their pharmaceutical use is to incorporate the drug into the system and thereby modify its solubility or delivery. 

Biological molecules do show regularity at the level that is not obtained with synthetic polymers. Protein folding is a perfect example, but it is not yet well understood. Therefore, protein-based 3D drug delivery systems are difficult to design. However, small peptides with amphiphilic structure (e.g., V6K, where six valines form hydrophobic part and lysine is the hydrophilic end group) can assemble... 

Yui s group has investigated biodegradable polymers based on the cyclodextrin-based polyrotaxanes over the course of the last decade [128-139]. First, they prepared polyrotaxanes from a-cyclodextrin and PEG bisamine (Scheme 23) [128]. For example, l-phenylalanine was employed as an enzymatically hydrolyzable endcap. The in vitro degradation experiments using papain showed that a-cyclo dextrin was indeed released only when the terminal peptide linkages were hydrolyzed. They have prepared various kinds of polyrotaxanes based on cyclodextrin and have demonstrated that these polyrotaxanes are effective as drug delivery systems. 

One of the earliest approaches to creating polymer-peptide hybrid materials was based on the introduction of peptide moieties in the polymer side chain [11]. These architectures have been of particular interest for the development of drug delivery systems with a high loading capacity as well as for systems in which case the bioactivity is related to having multiple copies of a peptide in close proximity of each other. 

Hormones, proteins, and small peptides are not suitable for oral administration without complex modifications in the formulation. A variety of approaches for insulin delivery, as a model drug, have been attempted to improve on its bioavailability. Advances have been realized in the delivery of insulin through oral, nasal, rectal, dermatologic, and ocular routes. Proteins can also be delivered transdermally, using a lipid-based, biphasic delivery system in therapeutic quantity. 

Bhadra, D., Bhadra, S. and Jain, N.K., PEGylated peptide-based dendritic nanoparticulate systems for delivery of artemether. Journal of Drug Delivery Science and Technology, 15(1), 65-2005. 

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