Study of drug delivery and cell encapsulation using biocompatible hydrogel

Hydrogel particles encapsulating biomolecules or living cells are becoming an attractive means to mediate drug delivery or facilitate cell-based treatment of diseases. These particles are capable of maintaining drug stability/cell viability and providing specific drug release profiles. The selection of specific hydrogel and particle size depends on the administration routes, properties of the therapeutics and desired release profiles, and dictates the fabrication methods. We have chosen to design and fabricate hydrogel particles as a means to improve the efficacy of drug delivery utilizing mechanical, hydrodynamic and electric forces (precision particle fabrication (PPF) method and its modified scheme). Using such precision particles, we studied the drug release mechanisms that may help improve the design of new drug delivery vehicles. Monodisperse gelatin microspheres, fabricated via the electric field assisted PPF method, allowed detailed analysis of drug release without uncertainties ascribable to nonuniform particles. The results from this analysis, including zeta potential, particle swelling ratio, and intraparticle drug distributions, led to a release model, based on the reaction-diffusion and Michaelis-Menten kinetics. This model elucidates the effect of glutaraldehyde, a cross-linking agent, on release profile in terms of the initial drug distribution, diffusivity, degradation rate of gelatin and its ability to form polyionic complex with the drug. By measuring the drug diffusion constant and initial intrapaticle drug distribution in advance, the model can predict the drug release and serve as a design tool for certain drug delivery scenarios. Hydrogel particles with peptide coating were developed as a vehicle for targeted delivery. The proposed drug delivery vehicle contains three main components: (1) anticancer drug, (2) targeting peptide, and (3) drug carrier. In this study, the peptide was used to target Cathepsin D that is overexpressed by breast cancer cells. Gelatin microspheres were utilized as drug carriers which immobilized doxorubicin, an anticancer drug. Uniform gelatin particles (30 µm in diameter, dry) were fabricated via the electric field assisted PPF method to optimize the drug loading efficiency. The particles suitable for intravenous injection (<10 µm, dry) were fabricated by increasing the electric field strength. The results of the release study and chemotherapy on cancer cells, performed in collaboration with Prof. Logan Liu’s group, confirmed that the use of peptide coating as a targeting moiety substantially enhanced the efficacy of chemotherapy, which would alleviate the adverse effect of chemotherapy ascribable to systemic distribution of chemotherapeutics. Alginate microspheres/microcapsules of precisely controlled size and size distribution were employed for cell encapsulation which could be utilized in cell-based therapy and artificial organs. Cell viability was shown to remain intact after the encapsulation. The cross-linking of alginate with calcium ion involved the motion of both alginate molecules and calcium ions. The observation of significant size shrinkage from alginate microdroplets to microspheres indicated a junction-zone mode of the cross-linking process. A particle sorting scheme combining optical detection and electric deflection was developed to deflect out capsules empty of cells and increase the yield in cell encapsulation. This may contribute to reducing the volume of microcapsules required for transplantation and make clinical application more practical. In summary, we have demonstrated the flexibility and practicality of the modified PPF method in producing precision hydrogel particles and the suitability of these particles for applications involving their applications for controlled drug delivery and tissue engineering.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Electrical & Computer Engr

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Cheng, Felice

Contributors dc:contributor

• Kim, Kyekyoon
• Choi, Hyungsoo
• O'Brien, William D.
• Hsieh, Kuang-Chien

• Hydrogel
• drug delivery
• cell encapsulation

Statement dc:rights

• Copyright 2010 Felice Cheng

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/18647

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/18647