Modern drug development technologies such as combinatorial chemistry and automated high-throughput screening have led to the identification of numerous potential new active pharmaceutical ingredients (APIs). However, many of those promising new molecules never reach market approval because they are not sufficiently soluble, cannot reach the desired target, are attacked by the immune system, are degraded by endogenous enzymes, or suffer from rapid renal clearance.

To overcome these restrictions, first attempts with polymers were made already in the 1960s – either by attaching the therapeutic agent covalently to a polymer or by entrapping it non-covalently in a polymer nanoparticle. The first polymer-drug conjugates that showed promising results contained poly(ethylene glycol) (PEG), and until today, PEG is the most widely used standard.

However, PEG is made of monomer units connected via an ether bond. This is a rather rare chemical bond in living nature and not used in natural biopolymers. Consequently, the human body does not possess suitable enzymes to degrade polyether molecules – leading to undesired accumulation of large PEG molecules in cells upon long-term treatment with high doses of PEG.

Besides, the increasing use of PEGs and PEGylated products in pharmaceutical research led to additional insights:

• PEGs, which were originally thought to be non-immunogenic, turned out to provoke immune reactions in several individuals.

• Adverse side effects in the body can be provoked by the polymer itself or by side products formed during synthesis that may lead to hypersensitivity.

• Unexpected changes in the pharmacokinetic behavior can occur with PEG-based carriers.

Biodegradable poly(amino acids) appear very attractive in this context. As with PEGs, the termini of these polymers can be equipped with various functionalizations to make the polymer more hydrophilic or more hydrophobic, inert, or reactive.

Poly(sarcosine) (PSar) – originating from the natural, non-toxic amino acid sarcosine (N-methylglycine) – is the simplest polypeptoid and a newly rediscovered biocompatible and degradable polymer. PSar is hydrophilic and shows excellent non-fouling properties, leading to protein-repellent surfaces and long-circulating polymers or polymer nanoparticles.

→ Don’t allow your creativity to be limited! Try out poly(sarcosine) for PEG replacement and discover its unique properties.
→ To support your research efforts, we offer special trial bundles at a discounted price (valid from beginning of May till end of July 2023).

Mal-PSar-OMe Bundle PSB1000 

NHS-PSar-OMe Bundle PSB1010 

MeO-PSar-COOH Bundle PSB1020 

N3-PSar-Ac Bundle PSB1030

Alkyne-PSar-Ac Bundle PSB1040 

• Find many poly(amino acid) derivatives in our section Drug Delivery

• For more detailed information, download our brochure Polymer Therapeutics 

References:

Suppressive immune response of poly-(sarcosine) chains in peptide-nanosheets in contrast to polymeric micelles; E. Hara, M. Ueda, C. J. Kim, A. Makino, I. Hara, E. Ozeki, S. Kimura; J. Pept. Sci. 2014; 20: 570-577. https://doi.org/10.1002/psc.2655.

Thermoresponsive release from poly(Glu(OMe))-block-poly(Sar) microcapsules with surface-grafting of poly(N-isopropylacrylamide); T. Kidchob, S. Kimura, Y. Imanishi; J. Control. Release 1998; 50: 205-14. https://doi.org/10.1016/s0168-3659(97)00135-1.

Amphiphilic poly(Ala)-b-poly(Sar) microspheres loaded with hydrophobic drug; T. Kidchob, S. Kimura, Y. Imanishi; J. Control. Release 1998; 51: 241-248. https://doi.org/10.1016/s0168-3659(97)00176-4.

On the biodegradability of polyethylene glycol, polypeptoids and poly(2-oxazoline)s; J. Ulbricht, R. Jordan, R. Luxenhofer; Biomaterials 2014; 35: 4848-4861. https://doi.org/10.1016/j.biomaterials.2014.02.029.

Polypeptoids: A Perfect Match for Molecular Definition and Macromolecular Engineering? R. Luxenhofer, C. Fetsch, A. Grossmann; J. Polym. Sci.: Part A: Polym. Chem. 2013; 51: 2731-2752. https://doi.org/10.1002/pola.26687.

Polysarcosine as an Alternative to PEG for Therapeutic Protein Conjugation; Y. Hu, Y. Hou, H. Wang, H. Lu; Bioconjugate Chem. 2018; 29(7): 2232-2238. https://doi.org/10.1021/acs.bioconjchem.8b00237.

Polysarcosine-containing copolymers: Synthesis, characterization, self-assembly, and applications; A. Birke, J. Ling, M. Barz; Prog. Polym. Sci. 2018; 81: 163-208; https://doi.org/10.1016/j.progpolymsci.2018.01.002.

Polysarcosine-Functionalized Lipid Nanoparticles for Therapeutic mRNA Delivery; S. Nogueira, A. Schlegel, K. Maxeiner, B. Weber, M. Barz, M. A. Schroer, C. E. Blanchet, D. Svergun, S. Ramishetti, D. Peer, P. Langguth, U. Sahin, H. Haas; ACS Appl. Nano Mater. 2020; 3(11): 10634-10645. https://doi.org/10.1021/acsanm.0c01834.