A pH‐sensitive nano drug delivery system derived from pullulan/doxorubicin conjugate

Abstract

A novel pH-sensitive nanoparticle drug delivery system for doxorubicin (DOX) is prepared. Pullulan, a natural biocompatible polysaccharide, was partly carboxymethylized; hydrazine hydrate was condensed with the carboxyl groups forming hydrazide. The hydrazide was coupled with DOX through the formation of hydrazone bond. The chemical structure of the conjugate was determined by FTIR and (1)H NMR. The pullulan/DOX conjugate nanoparticles were formed through the aggregation of hydrophobic DOX. The size and morphology of prepared nanoparticles were characterized using dynamic light scattering and transmission electron microscope. The results showed that the nanoparticles were spherical and their size was less than 100 nm. The content of DOX in conjugate was 3.18 wt %. The investigation of the release behavior in vitro indicated that the DOX was released from nanoparticles faster at pH 5.0 (62% DOX released within 24 h) than at pH 7.4 (29% DOX released within 24 h). The in vitro cytotoxicity of pullulan/DOX conjugate nanoparticles was tested by the MTT assay.

Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

“…Methylene protons of CMP were resolved between 4.1 and 5.6 ppm spectrum region corresponding to the four substitution sites namely O-2, O-3, O-4, and O-6. In DOX-CMP conjugate, peaks at 0.9 and 1.25 ppm for methyl and methylene of DOX were observed which confirmed conjugation of doxorubicin (Lu et al 2009). DOX-conjugated CMP was synthesized by hydrazone bond between CMP and DOX.…”

Natural Polysaccharide based Nanoparticles for Drug/Gene Deliv­ery

“…66 Pullulan-based nanoparticles have been successfully used for the enhanced delivery of doxorubicin into tumor cells. 70 Similarly, pullulan nanoparticles have been designed as mocuadhesive ocular drug delivery systems. 71 Pullulan has also been reported for the oral delivery, because of its biodegradable nature.…”

“…69 Besides, pullulan has shown anticancer activity. 70 Cholesteryl groupbearing pullulan (CHP) is a universal protein-based antigen delivery vehicle for adjuvant free nasal vaccination. CHP can self-assemble into nanoparticles in aqueous environment and encapsulate a large amount of therapeutic payloads in the interior space through hydrophobic interactions.…”

“…However this problem can be readily handled by the modification of nanoparticles with components such as fatty amines and cationic polyamines that decrease negative charge density in the polymer structure and enhance the loading capacity of siRNA. 70 In addition, HA nanoparticles loaded with siRNA and cisplatin were shown as promising carriers that could target CD44 receptors overexpressed in the cisplatin-resistant tumors.…”

In Vivo Evaluation of a pH‐Sensitive Pullulan–Doxorubicin Conjugate

“…[25] In our previous research, the fabrication, characterization and pH-sensitive drug release behavior of a novel pHsensitive pullulan-doxorubicin conjugate was reported. [26,27] Doxorubicin was conjugated onto pullulan through a pH-sensitive covalent bond, which is stable under neutral conditions and can rupture at decreased pH. Making use of differences in the structure and behavior between normal and tumor tissue, [16,28] this pH-sensitive pullulan-doxorubicin conjugate can release the bound drug in the changed pH environment in tumors, thus facilitating the tumor-selective delivery of doxorubicin.…”