Abstract

Modification of drug delivery materials with beta-cyclodextrins (β-CyD) is known to increase solubility of poorly water-soluble drugs, protect drugs from degradation and sustain release. In this study, we developed a hydrogel drug delivery system for local paclitaxel delivery using the natural polysaccharide alginate functionalized with β-CyD-moieties. Paclitaxel was chosen due to its ability to form inclusion complexes with cyclodextrins. The rheological and mechanical properties of the prepared hydrogels were characterized, as well as in vitro release of the paclitaxel and in vitro activity on PC-3 prostate cancer cells. Introduction of β-CyD-moieties into the hydrogel reduces the mechanical properties of the gels compared to nonmodified gels. However, gelation kinetics were not markedly different. Furthermore, the β-CyD-modified alginate helped to reduce undesired crystallization of the paclitaxel in the gel and facilitated paclitaxel diffusion out of the gel network. Remarkably, the β-CyD grafted alginate showed increased capacity to complex paclitaxel compared to free HPβ-CyD. Release of both paclitaxel and degradation products were measured from the gels and were shown to have cytotoxic effects on the PC-3 cells. The results indicate that functionalized alginate with β-CyDs has potential as a material for drug delivery systems.

Highlights

  • Local drug delivery gives an advantage compared to systemic therapy due to increased drug concentration at delivery site, less detrimental systemic side effects, and ease of administration.[1]

  • We conducted a series of experiments to characterize gelation kinetics and mechanical properties of the hydrogel system based on the modified alginate

  • We developed a hydrogel-based delivery system employing β-CyD functionalized alginate, where alginate acted as the gelling material and the β-CyD moieties were responsible for formation of inclusion complexes with a poorly soluble drug

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Summary

| INTRODUCTION

Local drug delivery gives an advantage compared to systemic therapy due to increased drug concentration at delivery site, less detrimental systemic side effects, and ease of administration.[1]. Injectable systems are advantageous due to their minimally invasive delivery, capacity to fill the cavity they are placed in, and ability to form a drug-loaded depot that can protect payload from enzymatic degradation and sustain drug release over a long period of time.[2] Many injectable in situ forming hydrogels have been developed, and their superior efficacy in animal models over conventional systemic therapy has been demonstrated.[3] As an example, an injectable hydrogel has been used for local delivery of paclitaxel for the treatment of glioblastoma in mice.[4] To design an efficacious hydrogelbased injectable system many parameters should be controlled, including biocompatibility, mechanical, and viscoelastic properties.[3]. In vitro release of the paclitaxel and in vitro cytotoxicity toward PC-3 prostate cancer cells was studied

| MATERIAL AND METHODS
| Methods
| RESULTS AND DISCUSSION
| CONCLUSIONS

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