PotM: Polysarcosines for Drug Delivery

Polysarcosine (PSR) – originating from the natural, non-toxic amino acid sarcosine (N-methylglycine) – is the simplest polypeptoid and serves as biocompatible and degradable polymer. Polysarcosines have been employed in a number of drug delivery systems, including dendrimers, polymer micelles, polyplexes, protein conjugates and nanoparticles, polymersomes and nanotubes.

Polysarcosines allow to improve solubility as well as chemical and physical stability, prolong in vivo half-life, decrease immunogenicity and toxicity and increase efficacy and clinical effectiveness in vivo. Furthermore, they are 100% biodegradable.

However, widespread use of PSR has been hampered by the lack of commercially-available functional PSR in good quality. In response to the increasing regulatory demand for drug delivery systems we are focused on high precision polymers.

Iris Biotech offers monofunctional, homo- and heterobifunctional Polysarcosines with a wide variety of functional groups. Degrees of polymerization (n) may range from below 10 to above 1.000. Thus, molar masses of approx. 1 kg/mol to 100 kg/mol are feasible.

They are characterized by the following properties:

• Biobased, degradable, and non-immunogenic
• Excellent water solubility and solubility in organic solvents
• Highly defined polymers with narrow Poisson distribution
• Mono-, homo- and heterobifunctional; customized functionalities on demand
• Excellent shelf-life, reproducibility and analytical purity

We provide narrow molecular weight distribution and reproducible and scalable manufacturing.

The use of Polysarcosines with functional head- and tail-groups for bioconjugation is comparable to the well-known PEGylation technology. In a study, a Polysarcosine- and PEG-conjugated Uricase were compared, and it was shown that the PSar conjugation is efficient in extending Uricase half-life in vivo more than 20-fold. Furthermore, PSar-Uricase is less immunogenic compared to either native or PEGylated Uricase in vivo, and polysarcosination did not affect the enzymatic activity.

Case Study Uricase: PEGylation vs. Polysarcosination

Check-out the related products to see our available catalogue items.

➔ Interested in other polysarcosines? Get in contact for a customized offer to match your material specifications, regulatory requirements, and functional needs.

References:

Molecular assembly composed of a dendrimer template and block polypeptides through stereocomplex formation; H. Matsui, M. Ueda, A. Makino, S. Kimura; Chem. Commun. 2012; 48: 6181-3. https://doi.org/10.1039/c2cc30926b.

Factors Influencing in Vivo Disposition of Polymeric Micelles on Multiple Administrations; E. Hara, M. Ueda, A. Makino, I. Hara, E. Ozeki, S. Kimura; ACS Med. Chem. Lett. 2014; 5: 873-877. https://doi.org/10.1021/ml500112u.

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. S. Nogueira, A. Schlegel, K. Maxeiner, B. Weber, M. Barz, M. A. Schroer, C. E. Blanchet, D. I. 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.