Polymer prodrug approaches applied to paclitaxel

Abstract

Paclitaxel possesses a unique mechanism of drug action as a new class of microtubule stabilizing agent which finally leads to disrupted mitosis and cell death. Recent findings have shown that paclitaxel initiates apoptosis through multiple mechanisms. However, the strong hydrophobicity of paclitaxel drastically limits its use in natural form. In addition, significant toxicity which is mainly ascribed to the non-specific, indiscriminate distribution among the tissues limited the application of paclitaxel in cancer therapy. Therefore, it remains of interest to improve their use by enhancing solubility, selectivity and in vivo delivery by preparing functional prodrugs selectively activable in tumour areas. This article summarizes results and information derived recently from paclitaxel prodrugs based mainly on macromolecular conjugates and their interactions with body fluids. We also explore the potential application of site-specific carriers in the development of tumor-targeting paclitaxel conjugates.

A polymeric prodrug of cisplatin based on pullulan for the targeted therapy against hepatocellular carcinoma

“…Polymeric prodrugs generally exhibit the enhanced in vivo stability, the prolonged half-life in blood, the improved water solubility, and the specific tumor-targeting property through enhanced permeability and retention (EPR) effect (Kratz et al, 2008;Greco and Vicent, 2009;Sohn et al, 2010;Sanchis et al, 2010). The potential of the polymeric prodrugs has already been proved by success of some products in the clinical oncology (Li and Wallace, 2008;Kratz, 2007;Banerjee et al, 2012).…”

Self‐Immolative Spacers: Kinetic Aspects, Structure–Property Relationships, and Applications

“…[1][2][3][4][5][6][7][8] Hencev arious strategies have been used to directly release active compounds from their protected precursors.However,when the protecting group or the active compound is bulky,p recursor activation may become difficult and the release of the desired compound not effective. This strategy permits to overcome limitations of free small molecules such as low water solubility,lack of specificity to the target, or suboptimal pharmacokinetics.P rotecting groups,w ell-established in organic chemistry,c an be useful to engineer such prodrugs:protection induces adecrease or elimination of the biological activity,t he masked compound is then released under specific biological conditions.…”

“…This strategy permits to overcome limitations of free small molecules such as low water solubility,lack of specificity to the target, or suboptimal pharmacokinetics.P rotecting groups,w ell-established in organic chemistry,c an be useful to engineer such prodrugs:protection induces adecrease or elimination of the biological activity,t he masked compound is then released under specific biological conditions. [1][2][3][4][5][6][7][8] Hencev arious strategies have been used to directly release active compounds from their protected precursors.However,when the protecting group or the active compound is bulky,p recursor activation may become difficult and the release of the desired compound not effective. [9] To overcome this limitation, an efficient and increasingly popular approach consists of decoupling precursor activation from compound release by introducing a" self-immolative spacer" between the protecting group and the active compound.…”

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

“…1 Although they are relatively potent and clinically active, the side effects associated with PTX including nausea, vomiting, diarrhea, mucositis, myelosuppression, cardiotoxicity, has 10 presented a serious concern in clinic. 2,3 Also, the clinical use of PTX is limited by its poor water solubility (~ 0.3 µg/mL) and pharmacokinetic characteristics, high systemic exposure and the lack of selective tumor uptake, which decreases the intracellular drug accumulation and reduces the efficacy of cancer 15 chemotherapy. 4 In the past decades, a variety of biocompatible nanocarriers such as polymeric micro/nanoparticles, liposomes, polymersomes and water-soluble prodrugs have been developed in order to reduce these adverse effects.…”

“…4 In the past decades, a variety of biocompatible nanocarriers such as polymeric micro/nanoparticles, liposomes, polymersomes and water-soluble prodrugs have been developed in order to reduce these adverse effects. 2,3,[5][6][7][8] Among the various polymer-based nanocarriers, 20 polymeric micelles self-assembled from amphiphilic block copolymers showed great potential on applications as nanocarriers of chemotherapeutic drugs and imaging agents. [9][10][11][12][13] In general, most of the polymeric micelles loaded drugs via noncovalent interactions.…”