Periodic Reporting for period 1 - NanoCap (Sustainable Polypeptide Nanoparticle Platform for Drug Delivery)
Reporting period: 2016-04-01 to 2018-03-31
Numerous examples in the academic and patent literature discuss enhanced biocompatibility, superior cargo encapsulation, and convenient release profiles for a number of cargoes from biodegradable nanoparticles to be used in a variety of applications in the field of medicine and cosmetics. Most widely used are polymeric nanoparticles based on natural polymers have advantages and drawbacks, making them more or less suited for certain application areas, e.g. natural polymers usually have a good biocompatibility. However, obtaining reproducible sample quality from natural sources is challenging. PLGA can be produced reproducibly but is hydrophobic in nature, which makes loading of hydrophilic drugs challenging. Next generation carrier systems should offer enhanced functionality to readily enable loading with multiple classes of active agents, allow chemical modification, bioconjugation or diagnostic labelling, if needed. Moreover, they should be easy to produce from natural building blocks, omitting the use of harsh synthetic agents. While the pharmaceutical/medical sector is more conservative, for the cosmetic sector it was stated, that “Terms such as ‘natural’, ‘organic’, ‘no artificial preservatives’ and ‘no animal ingredients’ are drawing formidable attention. This trend is creating heightened demand for products formulated as cosmeceuticals with natural and nutraceutical ingredients. Functional ingredients and innovative delivery systems are driving the new product development arena.”
The overall objective of this project is to develop a new biodegradable polypeptide nanomaterials platform and demonstrate its technical feasibility as nano-carrier platform for active ingredients for Life Science applications exclusively from amino acid building blocks. A series of copolypeptides was synthesized and their structure verified. These were successfully formulated into nanoparticles of 200-300 nm diameter and it was demonstrated that dyes as well as drug molecules can be loaded into the polypeptide nanoparticles. The simple preparation method of synthetic polypeptide nanoparticles will be useful as an advanced technology to develop fully biodegradable nanoparticles used as nanocarriers for active ingredients in biomedical science application.
In the second part of the project the range of cargo types that can be successfully encapsulated within the polypeptide nanoparticles was investigated in order to determine the scope of their utility. In the first instance a simple model dye rhodamine B was incorporated into the hydrophobic nanoparticles. Rhodamine B-loaded nanoparticles showed mostly spherical morphology with a average diameter of ca. 260 nm. In the following stage indomethacine, a model anti-inflammatory drug was used. Indomethacin is a poorly water-soluble drug used to reduce pain, fever, and inflammation. Indomethacine could be efficiently loaded into the nanoparticles owing to the hydrophobic interaction. In order to meet primary requirements for biomedical use, the degradation profiles of the statistical copolypeptide nanoparticles were tested in a preliminary in vitro hydrolysis study. Degradation of the nanoparticles was thus studied by DLS over the period of 4 weeks. The nanoparticles were prepared in distilled deionized water and PBS buffer and then degraded at 37°C. The average nanoparticle size in water decreased initially, and then levelled off after 7 days. The nanoparticle size then increased dramatically after 14 days, indicating significant aggregation. On the other hand, the average nanoparticle size in PBS buffer remains constant for 24 days followed by significant aggregation as determined by DLS analysis.
It is expected that research activities on this project will result in 1 or 2 papers. During my Marie Skłodowska-Curie Individual Research Fellowship at RCSI I have also worked on a side project, which has resulted in the synthesis of novel poly(tert-butyl acrylate)-xanthate macroinitiator as a precursor for RAFT polymerization with N-vinylpyrrolidone. The result of this work has been presented as a poster at the European Polymer Conference in Lyon (EPF2017, MO 017-147049). In addition, I have attended the Marie Skłodowska-Curie alumni association conference (Leuven, February 2nd-3rd 2018) which enabled me to participate in career development events such as workshops on funding and employment opportunities.