A dual stimuli-responsive star-shaped nanocarrier as de novo drug delivery system for chemotherapy of solid tumors
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A dual stimuli-responsive star-shaped nanocarrier as de novo drug delivery system for chemotherapy of solid tumors Sanaz Motamedi 1 & Bakhshali Massoumi 1 & Mehdi Jaymand 2
&
Hamed Hamishehkar 3
Received: 12 December 2019 / Accepted: 16 April 2020 # The Polymer Society, Taipei 2020
Abstract A novel pH- and temperature-responsive star-shaped terpolymer, namely star shaped-poly(ε-caprolactone)-grafted-[poly(N,N′dimethylamino)ethyl methacrylate-block-poly(N-isopropylacrylamide)] [s-PCL-g-(PDMAEMA-b-PNIPAAm)], was synthesized by combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP), and its potential as smart drug delivery system (DDS) for chemotherapy of solid tumors (human breast cancer) was investigated preliminary. The structure of the fabricated polymers were characterized using Fourier transform infrared (FTIR) and proton magnetic resonance (1H NMR) spectroscopies. The average molecular weights of the synthesized polymers were calculated using both 1H NMR spectroscopy and gel permeation chromatography (GPC) analysis. The self-assembly behavior of the fabricated s-PCLg-(PDMAEMA-b-PNIPAAm) terpolymer under pH and thermal stimuli were investigated using dynamic light scattering (DLS) equipment. The methotrexate (MTX) loading capacity of the fabricated DDS was calculated to be 36.9 ± 4.1%. As pHand thermal-triggered drug release behavior results, at pH 5 and temperature of 41 °C, the developed DDS exhibited higher drug release value, which qualified it for cancer chemotherapy according to abnormal environmental feature of cancerous cells. The MTX-loaded terpolymer exhibited higher anticancer efficiency in comparison with free MTX especially in time period of 48 h, mainly due to its slow drug release behavior as well as long circulation time of the developed DDS. Keywords Star-shaped copolymer . Stimuli-responsive . Self-assembly . Drug delivery . Cancer chemotherapy
Introduction It is a predictable fact that cancer will soon become the most important healthcare issue with an increasing incidence worldwide. Therefore, more and more research efforts have been focused on the development of novel and efficient treatment approaches. It is worth noting that conventional treatment approaches such as radiation- or chemotherapy treat both
* Bakhshali Massoumi [email protected]; [email protected] * Mehdi Jaymand [email protected]; [email protected]; [email protected] 1
Department of Chemistry, Payame Noor University, Tehran, Iran
2
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
3
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
cancerous and surrounding normal tissues simultaneously, that lead to poor therapeutic effect on tumors as well as numerous side effects, including hair loss, nausea, and vomiting when administered at high dose systematically [1–3]. In this context, polymeric stimuli-responsive drug delivery systems (DD
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