Master assignment - PAA Nanogels for Drug Delivery

Poly(Amido Amine) Nanogels for Drug Delivery

Background
Dispersed nano-sized water-soluble polymer networks, or nanogels respond to environmental factors such as pH and temperature and have a wide variety of biomedical applications.1 At the department of Controlled Drug Delivery synthesis and application of poly(amido amine)s (PAAs) are important topics of research.2–4 PAAs are a versatile, water-soluble and biocompatible class of polymers, whose structures mimics that of peptides, enhancing their biocompatibility. PAA nanogels can be formed by an inverse nanoprecipitation method, as shown in Figure 1.5 Bioreducible disulfide groups can be introduced into the nanogels by using cystamine disulfide as a crosslinker.

Figure 2: General process of inverse nanoprecipitation. The PAA is dissolved in water and added to a non-solvent, which contains the crosslinker. After the reaction has been completed the non-solvent is removed and the particles are purified.

Aim of the Project

The aim of the project is to encapsulate therapeutic molecules into nanogels by co-precipitation and subsequent crosslinking of the polymer in Figure 2.6 The initial approach will be to physically encapsulate molecules like Rifampicin, for the controlled release of antibiotics, and Doxorubicin, for the targeted chemotherapeutic delivery. To improve encapsulation efficiency methods like the synthesis a functional co-polymer, chemical ligation or the use of host-guest complexes can be considered.

Figure 2: PAA structure for nanogel formation

Approach

Functional PAAs will be synthesized and nanogels will be formed in the presence of e.g. Rifampicin or Doxorubicin. The encapsulation efficiency and release profile will be researched. Finally the drug-loaded nanogels can be tested in vitro as a proof of concept.

Contact information

Tony Ekkelenkamp – Biomaterial Science & Technology
Dr. Jos Paulusse – Biomaterial Science & Technology

Email: a.e.ekkelenkamp@utwente.nl
Phone: 053 - 489 2988
Room: ZH 244

References

(1) Kabanov, A. V; Vinogradov, S. V. Angew. Chem. Int. Ed. 2009, 48, 5418–5429.

(2) Van der Aa, L. J.; Vader, P.; Storm, G.; Schiffelers, R. M.; Engbersen, J. F. J. J. Control. release 2011, 150, 177–186.

(3) Lin, C.; Zhong, Z.; Lok, M. C.; Jiang, X.; Hennink, W. E.; Feijen, J.; Engbersen, J. F. J. J. Control. release 2006, 116, 130–137.

(4) Martello, F.; Piest, M.; Engbersen, J. F. J.; Ferruti, P. J. Control. release 2012, 164, 372–379.

(5) Steinhilber, D.; Witting, M.; Zhang, X.; Staegemann, M.; Paulus, F.; Friess, W.; Küchler, S.; Haag, R. J. Control. Release 2013, 169, 289–295.

(6) Ryu, J.-H.; Chacko, R. T.; Jiwpanich, S.; Bickerton, S.; Babu, R. P.; Thayumanavan, S. J. Am. Chem. Soc. 2010, 132, 17227–17235.