pH/NIR-Responsive Polypyrrole-Functionalized Fibrous Localized Drug-Delivery Platform for Synergistic Cancer Therapy

Abstract

Localized drug-delivery systems (LDDSs) are a promising approach for cancer treatment because they decrease systematic toxicity and enhance the therapeutic effect of the drugs via site-specific delivery of active compounds and possible gradual release. However, the development of LDDS with rationally controlled drug release and intelligent functionality holds great challenge. To this end, we have developed a tailorable fibrous site-specific drug-delivery platform functionalized with pH- and near-infrared (NIR)-responsive polypyrrole (PPy), with the aim of cancer treatment via a combination of photothermal ablation and chemotherapy. First, a paclitaxel (PTX)-loaded polycaprolactone (PCL) (PCL-PTX) mat was prepared by electrospinning and subsequently in situ membrane surface-functionalized with different concentrations of PPy. The obtained PPy-functionalized mats exhibited excellent photostability and heating property in response to NIR exposure. PPy-coated mats exhibited enhanced PTX release in a pH 5.5 environment compared to pH 7.4. Release was further accelerated in response to NIR under both conditions; however, superior release was observed at pH 5.5 compared to pH 7.4, indicating a dual stimuli-responsive (pH and NIR) drug-delivery platform. More importantly, the 808 nm NIR irradiation enabled markedly accelerated PTX release from PPy-coated PCL-PTX mats and slowed and sustained release following termination of laser irradiation, confirming representative stepwise drug-release properties. PPy-coated PCL-PTX mats presented significantly enhanced in vitro and in vivo anticancer efficacy under NIR irradiation compared to PPy-coated PCL-PTX mats not exposed to NIR or uncoated mats (PCL-PTX). This study has thus developed a promising fibrous site-specific drug-delivery platform with NIR- and pH-triggering that notably utilizes PPy as a dopant for synergistic photothermal chemotherapy.

The incorporation and controlled release of dopamine from a sulfonated β–cyclodextrin–doped conducting polymer

“…When the PPy-sβ-CD is oxidised, the positively charged backbone will exert repulsive forces on the included DA and these seem to be sufficiently strong to release DA from the cavity. While many of the recent publications [8][9][10][11][12][13][14][15][16][17][18] have focused on increasing the polymer surface area to give higher release rates, these results show that the nature of the dopant is equally important. Furthermore, the applied release potentials used in this study are very low at 0.10 V vs SCE and these can be easily reached without the application of an external potential.…”

“…While an increase in polymer thickness generally gives rise to an increase in the concentration of the drug released, thicker polymer films tend to become less electroactive. More recent attempts to increase the loading and concentration of the drug, include increasing the surface area of the polymer [8] by forming various polymer nanostructures [9,10], polymer nanoparticles/particles [11][12][13] or nanowires [14], fibres [15,16], nanotubes [17] and reservoirs that can be used to load the drug [18].…”

“…In terms of a comparison between polypyrrole and other drug delivery materials, polypyrrole is not biodegradable and while it can be formed as nanowires, nanoparticles and nanotubes [11][12][13][14][15][16][17], it is not suitable as a carrier to deliver drugs to specific sites in the body. For these applications biodegradable polymer nanogels [26,27] are attracting considerable interest as they have the potential to deliver drugs to the target cells.…”

A Review on Properties of Natural and Synthetic Based Electrospun Fibrous Materials for Bone Tissue Engineering

“…PCL is semi-crystalline polyester with glass transition temperature of nearly −60 °C and melting point of 61 °C. Because of multiple advantages like biocompatibility, non-toxicity, biodegradability, and adequate mechanical properties, PCL is widely used in biomedical applications [ 130 ]. Furthermore, relatively slow degradation rate and high modulus value makes the PCL mat, a good choice for bone tissue and drug delivery application.…”

Electrodeposited Copolymer Films with Tunable Conductivity

“…Among heterocyclic conducting polymers, considerable attention has been drawn to electrodeposited polypyrrole and its derivatives because of their high conductivity, thermal and environmental stability, and ease of electrosynthesis [5,6]. To date, polypyrrole films have been used for various applications including: batteries and energy storage [7][8][9], tissue engineering [10], drug delivery [11], cytometry [12,13], and biosensors [5].…”