Investigation of dual-sensitive nanogels based on chitosan andN-isopropylacrylamide and its intelligent drug delivery of 10-hydroxycamptothecine

Abstract

The work was to prepare and characterize a responsive drug delivery system built of chitosan-g-poly (N-isopropylacrylamide) (CTS-g-PNIPAAm) nanogels and to evaluate the effects of CTS molecular weight (Mw) on the loading and in vitro release of insoluble drug 10-hydroxycamptothecine (HCPT). The CTS-g-PNIPAAm copolymers were synthesized by radical polymerization. The Mw and physical chemistry properties such as diameter, second virial coefficient of grafted PNIPAAm were investigated by dynamic and static laser light scattering method. A series of cross-linked CTS-g-PNIPAAm nanogels were prepared with N, N'-methylenebisacrylamide initially added as a cross-linker. The thermal and pH-sensitive features of cross-linked CTS-g-PNIPAAm nanogels were studied by determining the variance of transmittance, changeable size and reversed zeta potential. The critical aggregation concentrations (CAC) of resultant nanogels decreased from 0.045 to 0.036 mg/mL with CTS Mw increased from 50 kDa to 700 kDa. The loading efficiency of the HCPT encapsulated into CTS-g-PNIPAAm nanogels increased in parallel with CTS Mw, while the cumulative release percentage of HCPT-loaded nanogels decreased with CTS Mw increasing at both 25 °C and 37 °C. Fitting results of HCPT release data to different mathematical models suggested a diffusion-controlled mechanism at 25 °C. However, the release behaviors were dominated by combined effects of polymer erosion and osmotic pressure driven at 37 °C. The cytotoxicity study of the CTS-g-PNIPAAm nanogels against hepatic L02 cells indicated that the resultant nanogels did not exhibit apparent cytotoxicity.

Advances in Stimuli‐Responsive Chitosan Hydrogels for Drug Delivery Systems

“…Temperature is critical in human physiology and can be conveniently controlled in both in vitro and in vivo conditions. [ 67 ] Thus, temperature‐responsive hydrogels have attracted much attention in the past few decades. [ 68–70 ] Among various modifications, the poly (N‐isopropylacrylamide) (PNIPAM) is the most frequently used homopolymer.…”

A dual‐stimuli responsive supramolecular nanovector anchoring folic acid ligands for targeted delivery of anti‐colorectal drug hydroxycamptothecin

“…Zhu et al reported dual-sensitive nanogels based on chitosan and N-isopropylacrylamide for HCPT intelligent delivery on Liver L02 Cells. 15 Xu et al reported microenvironment-responsive chemotherapeutic nanogels delivering HCPT to enhance 4 T1 breast cancer therapy via DNA damage and glutathione consumption. 3 However, due to the complicated human microenvironment, existing stimulus-responsive nanocarriers can only passively deliver drugs without achieving the desired therapeutic effect, that is, passive accumulation of anticancer drugs in solid tumors through enhanced penetration and retention (EPR) effects.…”

“…Multi‐stimulus‐responsive nanocarriers, especially, usually possess higher sensitivity and efficiency of drug release. Zhu et al reported dual‐sensitive nanogels based on chitosan and N ‐isopropylacrylamide for HCPT intelligent delivery on Liver L02 Cells 15 . Xu et al reported microenvironment‐responsive chemotherapeutic nanogels delivering HCPT to enhance 4 T1 breast cancer therapy via DNA damage and glutathione consumption 3 .…”

Application of Polymerization Activator in the Course of Synthesis of N-Isopropylacrylamide Derivatives for Thermally Triggered Release of Naproxen Sodium

“…The biggest challenge in designing new structures is their rapid response to external stimuli. The parameters that still need improvement are the mechanical durability, biocompatibility, and for internal use, biodegradability [ 8 , 9 , 10 ]. Thermosensitive, water-soluble polymers have their specific properties because of the presence of hydrophobic mostly methyl, ethyl, and propyl groups.…”