Delivery Platform for Hydrophobic Drugs:  Prodrug Approach Combined with Self-Assembled Multilayers

Abstract

We report the design of a platform for the delivery of hydrophobic drugs via a macromolecular prodrug approach combined with LbL-assembled polyelectrolyte multilayers. A hyaluronan ester prodrug of the chemotherapeutic drug paclitaxel has been synthesized. Conjugation of the drug to hyaluronan through a labile succinate ester did not inhibit its activity. Using quartz crystal microbalance, atomic force microscopy, and UV spectroscopy, we have shown that the presence of the hydrophobic paclitaxel moieties does not prohibit the layer-by-layer construction of the multilayers. Release of the drug from the paclitaxel-loaded multilayers upon hydrolysis of the ester linkage resulted in a drastic cell death. Application of this delivery platform to substrates such as colloids, biomedical implants, or vascular tissues may lead to new therapeutic strategies.

Poly-cyclodextrin and poly-paclitaxel nano-assembly for anticancer therapy

“…2). Among the combinations of pCD and pPTX conjugates, pCD 20 and pPTX 7 were used for further study due to their enhanced water solubility. The pPTX/pCD (molar ratio of PTX/CD ¼ 1:1) nano-assembly was formulated by dissolving the two polymer conjugates in a water-ethanol solution, followed by freeze drying.…”

“…The reaction was monitored by TLC (silica plate; eluent, Formation of the pPTX/pCD nano-assembly. Two polymer conjugates, pCD 20 and pPTX 7 (molar ratio of PTX/CD ¼ 1), were dissolved in 20% (v/v) ethanol solution to obtain a 0.1% (w/v) PTX solution. This solution was stirred for 12 h at 25°C and then lyophilized.…”

“…As controls, PTX/pCD 20 and pPTX 7 were formulated using a similar method. In the case of PTX/pCD 20 , free PTX was used instead of pPTX 7 . For pPTX 7 , no CD molecules were added during the formulation process.…”

“…Polymeric delivery systems can also enhance the aqueous solubility and modify the pharmacokinetics and biodistribution of lipophilic drugs [5][6][7][8][9][10][11][12] . However, not all polymeric nanocarriers work efficiently.…”

Assembly‐Controlled Biocompatible Interface on a Microchip: Strategy to Highly Efficient Proteolysis

“…So far, they have been usually used for tissue engineering or drug delivery. [10] We have proposed a simple method with this self-assembly for imbedding enzymes on microchips for protein identification.…”