Self-Assembling Peptide Formulations for Drug Delivery

In this interview, Sotirios Koutsopoulos, Research Scientist at the Center for Biomedical Engineering at Massachusetts Institute of Technology, discusses the latest research in designer self-assembling peptides, injectable peptide hydrogel for targeted delivery of small drug compounds and proteins, and the direction of their future work.

  Pharma IQ: Can you tell us about the latest research in:

(a) Designer self assembling peptides?

  S Koutsopoulos: We have discovered that a class of self-assembling peptides comprised of alternating hydrophobic and hydrophilic amino acids spontaneously self-organize into interwoven nanofibers with diameters of 10–20 nm upon being introduced to lectrolyte solutions. These nanofibers further organize to form highly hydrated hydrogels
(up to ~99.5% w/v water), with pore sizes between 5 – 200 nm in diameter.

Peptide hydrogels not only have all the advantages of ‘traditional’ hydrogels, but also do not use harmful materials (e.g., toxic cross-linkers, etc.) to initiate the sol-gel transformation while the degradation products are natural amino acids, which can be metabolized by cells. The fact that the sol-gel transition occurs at physiological conditions and the high internal hydration of the hydrogel allows for the presentation of bioactive molecules and/or cells which may be co-injected locally in a tissue-specific manner. Self-assembling peptide hydrogel scaffolds are biocompatible, amenable to molecular design, and have been used in a number of tissue engineering applications including bone and
cartilage reconstruction, heart tissue regeneration, angiogenesis, and more.

Peptide hydrogels provide a platform that makes them ideal for nanomedical applications they are easy to use, non-toxic, non-immunogenic, non-thrombogenic, biodegradable, and applicable to localized therapies through injection to a particular tissue.

(b) Injectable peptide hydrogel for targeted delivery of small drug compounds and proteins?

S Koutsopoulos: Previously, a nanofiber hydrogel consisting of the self-assembling peptide ac-(RADA)4-CONH2 (where R is arginine, A is alanine and D is aspartic acid) was studied for controlled release of small, model-drug molecules and of proteins with different molecular weights and isoelectric points for periods of time between 3 days and 1 week. More recently, the sustained release of human immunoglobulin through injectable ac-(RADA)4-CONH2 and ac-(KLDL)3-CONH2 self assembling peptide hydrogels was studied for a period of 3 months. The release kinetics of the diffusing drug molecule through the ydrogels depend on the amino acid sequence of the self assembling peptides which form the hydrogel and on the density of the peptide nanofibers in the hydrogel.

The self assembling peptide system will gel upon injection intramuscularly, subcutaneously, in the void space of the brain, in the knee joint, or in any other tissue and release therein the therapeutic antibody. This peptide hydrogel system allows for 100% loading efficiency of the active therapeutic compound inside the hydrogels whereas, due to the consistency of he hydrogel (i.e., contains water up to 99.5 %), the maximum amount of drug loading
depends solely on the solubility of the drug in water.

One of the main goals of sustained drug delivery is to efficiently direct therapies to specific tissues. In cases of drugs with side effects localized delivery will result in less toxicity side effects on patients. The injectable self-assembling peptide system, which gels under physiological conditions, has the potential to be a robust system for sustained release pplications including immunotherapies to release active antibodies locally in specific issues over prolonged periods of time.

(c) Where do you see the future of this research going?

S Koutsopoulos: Our results present an opportunity to create new tailor-made, programmable and multi-layered peptide hydrogels for sustained release of small drug molecules, biomolecules, cytokines, antibodies, and other proteins. Peptide hydrogel systems can be easily designed and synthesized. The programmability of the peptide sequence provides a means of controlling the nanofiber properties at the molecular level which, in turn, alter the biomolecular diffusion and release kinetics. It is anticipated that urther fine-tuning of the peptide hydrogel systems will allow for a wide range of
applications in biomedical technology.

Future work will be focused on the release of therapeutic molecules like insulin to treat diabetes, hormones, growth factors, cancer drugs and eye medications. Furthermore, we want to explore the pharmacokinetics and biodistribution in animals and ultimately in humans. The peptide hydrogel system has been tested in humans with success. This will facilitate the transfer of peptide hydrogel drug delivery technology from bench to bedside.

The peptide hydrogel system can be used by physicians or nurses with minimal training who can prepare the drug formulation and adjust the release of the therapeutic compound to the desired timeframe on site, simply by mixing the appropriate amount of peptide solution with the drug compound. This will address each patient’s personal needs for optimal therapy because the patient will receive a treatment that will last as long as the prescription requires and optimal dosing which will eliminate toxic side effects. The biocompatible and injectable peptide hydrogel system is an ideal material for personalized therapies.

Sotirios Koutsopoulos will be speaking indepth on this topic at the upcoming IQPC Protein Formulation Development Summit, September 10 to 12, 2012 in Boston. For more information or to register, visit or email

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