Dually Responsive Poly( N -vinylcaprolactam)- b -poly(dimethylsiloxane)- b -poly( N -vinylcaprolactam) Polymersomes for Controlled Delivery.
Veronika KozlovskayaYiming YangFei LiuKevin A IngleAftab AhmadGanesh V HaladeEugenia KharlampievaPublished in: Molecules (Basel, Switzerland) (2022)
Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly( N -vinylcaprolactam) (PVCL)- b -poly(dimethylsiloxane) (PDMS)- b -PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material's toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL 10 - b -PDMS 65 - b -PVCL 10 vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg -1 single dose) of PVCL 10 -PDMS 65 -PVCL 10 vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research.
Keyphrases
- cancer therapy
- drug delivery
- drug release
- small molecule
- oxidative stress
- high resolution
- human health
- healthcare
- liver failure
- emergency department
- magnetic resonance
- high dose
- risk assessment
- low dose
- type diabetes
- intensive care unit
- single molecule
- current status
- hepatitis b virus
- adverse drug
- extracorporeal membrane oxygenation
- structural basis
- mechanical ventilation