Polymer platforms for drug delivery and biomedical imaging

Abstract

Biocompatible synthetic polymers have demonstrated advantageous pharmacokinetic properties as compared to small molecular agents. Incorporation of low molecular weight therapeutics and imaging agents into biocompatible polymers can optimize their pharmacokinetic properties with improved efficacy of therapy and diagnostic imaging, respectively. We have applied the concept of drug delivery to design safe and effective contrast agents for magnetic resonance imaging (MRI) and used biomedical imaging in non-invasive evaluation of drug delivery and image-guided therapy. We summarize here the recent progress in our research on biodegradable macromolecular MRI contrast agents, non-invasive visualization of in vivo drug delivery of polymeric conjugates with contrast enhanced MRI, and contrast enhanced MRI guided photodynamic therapy. The preliminary results have shown that biocompatible polymers can be used as an effective platform for drug delivery and biomedical imaging. Safe and effective imaging agents can be designed by using the concept of polymeric drug delivery. Biomedical imaging can be used as a non-invasive method for the evaluation of in vivo drug delivery of polymeric drug delivery systems. The combination of drug delivery and biomedical imaging can result in image-guided therapies, which include tumor detection, therapy and non-invasive evaluation of therapeutic responses.Biocompatible and water-soluble polymers have demonstrated unique pharmacokinetic properties, including prolonged blood circulation and tissue retention, and preferential accumulation in lesions with blood vessel hyperpermeability, because of their large sizes. Biocompatible synthetic polymers have been used as a platform for the modification of pharmacokinetics of small molecular therapeutics and imaging agents to improve their efficacy in drug delivery and molecular imaging [1,2]. The conjugation of therapeutics to biocompatible polymers prolongs in vivo drug retention time, increases drug bioavailability, reduces systemic toxicity and enhances therapeutic efficacy [3,4]. The incorporation of imaging agents into biocompatible polymers prolongs their retention in the tissues of interest with increased concentrations, which allows more accurate disease detection and characterization [5,6]. For example, the incorporation of a magnetic resonance imaging (MRI) contrast agent into a macromolecule would increase its blood circulation time for effective contrast enhanced cardiovascular imaging and tumor imaging [7,8].Both drug delivery and molecular imaging can benefit from the large sizes and unique pharmacokinetic properties of biomedical polymers. However, the applications of biomedical polymers in these areas are not mutually exclusive. In fact, the concept of drug delivery can be applied in molecular imaging to design and develop effective and specific imaging agents Correspondence to: Dr. Zheng-Rong Lu, 421 Wakara Way, Suite 318, Salt Lake City, UT 84108, Phone: 801 587-9450, Fax: 801 585-3614, Email: E-mail: zhengrong.lu@utah.edu....

Nanotechnology for biomedical applications - enhancement of photodynamic activity by nanomaterials

“…It was demonstrated that platforms to deliver only singlet oxygen, while conserving the embedded photosensitizer, may be synthesized [88]. Moreover, nanocarriers can contain not only photosensitizers particles, but also MRI contrast agents [89]. Optimal time of drugs systematic circulation can be ensured by modifying nanoparticles size (e.g.…”

Multifunctional Polymeric Nanostructures for Therapy and Diagnosis

“…These high density surface groups can be conjugated to drug molecules, targeting moieties and imaging agents, rendering dendrimers a versatile drug delivery platform. Surface groups on dendrimers can be modified to modulate cytotoxicity and permeation across biological barriers [100][101][102][103][104][105].…”

Dendrimers as carriers for contrast agents in magnetic resonance imaging

“…These agents were anticipated to be beneficial for the accumulation of MRI labels at regions of interest and allowed bimodality in imaging, thereby integrating the advantages of different imaging techniques [86][87][88]. Therefore, dendrimers were uniquely qualified to establish this site-specific system as the carriers with large numbers of reactive functional groups on the surface [89][90][91].…”

“…Other carbohydrate-functionalized dendritic agents with a bivalent fluorescent label and dendrimers with multiple gadolinium chelates and multiple oligopeptides for targeting were reported. Dendritic target-specific MRI contrast agents based on a biotinylated oligopeptide equipped with Gd(III)DTPA and avidin, and dendritic contrast agents composed of Gd(III)DTPA and oligopeptides were studied previously ( Figure 4) [87,[98][99][100][101].…”

“…(a) Multivalent target-specific contrast agents based on a biotinylated oligopeptide equipped with Gd(III)DTPA and avidin; (b) dendritic contrast agents composed of Gd(III)DTPA and oligopeptides[87,[98][99][100][101].…”