<p>Temperature and pH-responsive nano-hydrogel drug delivery system based on lysine-modified poly (vinylcaprolactam)</p>

Abstract

Background Smart materials capable of responding to external stimuli are noteworthy candidates in designing drug delivery systems. In many of the recent research, temperature and pH have been recognized as the main stimulating factors in designing systems for anti-cancer drugs delivery systems. Purpose In this study, thermo and pH-responsive character of a nano-carrier drug delivery platform based on lysine modified poly (vinylcaprolactam) hydrogel conjugated with doxorubicin was assessed. Methods Poly (vinylcaprolactam) cross-linked with poly (ethyleneglycol) diacrylate was prepared via RAFT polymerization, and the prepared structure was linked with lysine through ring-opening. The anti-cancer drug doxorubicin, was linked to lysine moiety of the prepared structure via Schiff-base reaction. The prepared platform was characterized by 1 HNMR and FT-IR, while molecular weight characterization was performed by size exclusion chromatography. The temperature-responsive activity was evaluated using differential scanning calorimetry and dynamic light scattering. In vitro release pattern in simulated physiologic pH at 37°C was compared with acidic pH attributed to tumor site and elevated temperature. The anticancer efficiency of the drug-conjugated structure was evaluated in breast cancer cell line MCF-7 in 24 and 48 h, and cell uptake assay was performed on the same cell line. Conclusion According to the results, well-structure defined smart pH and temperature responsive nano-hydrogel was prepared. The enhanced release rates are observed at acidic pH and elevated temperature. We have concluded that the doxorubicin-conjugated nanoparticle results in higher cellular uptakes and more cytotoxicity.

<p>In vitro and in vivo Evaluation of Succinic Acid-Substituted Mesoporous Silica for Ammonia Adsorption: Potential Application in the Management of Hepatic Encephalopathy</p>

“…For labeling MS nanoparticles, rhodamine B was covalently conjugated to these particles as previously described (with some modifications). 33 Briefly, rhodamine B (0.06 mmol) was activated in in dimethylformamide (DMF) (4 mL) solution containing N-hydroxysuccinimide (0.12 mmol) and 1-ethyl-3-(3dimethylaminopropyl) carbodiimide (EDC) (0.06 mmol) for 30 min at room temperature and then MS-NH 2 was added and stirred vigorously for 24 h (25°C, in the dark). Afterward, samples were vacuum dried and washed with DMF to remove un-reacted rhodamine B.…”

“…For labeling MS nanoparticles, rhodamine B was covalently conjugated to these particles as previously described (with some modifications). 33…”

Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo

“…For example, the poor oxygen perfusion in most kinds of tumor cells causes the elevated levels of lactic acid, resulting in weakly acidic extracellular and intracellular tumor microenvironments (Wojtkowiak et al, 2011). Lots of researchers have reported that the weakly acidic microenvironment could be used as the specific cue for anticancer drug delivery and controlled release (Huang et al, 2017;Niu et al, 2018;Farjadian et al, 2019;Limeres et al, 2019). For instance, Zhang et al reported a pH-sensitive PM which was self-assembled from poly(ethylene glycol) methyl ether-b-peptide-g-cholesterol (mPEG-b-P-g-Chol) for DOX delivery and controlled release.…”

Advances and trends of hydrogel therapy platform in localized tumor treatment: A review

“…The evidence that DOX‐loaded hydrogel performed better than the DOX solution group in anticancer experiment against nonsmall‐cell lung cancer cells A549, and the pH‐responsive capacity exhibited by hydrogel composite also proved the utilization potentiality of this strategy. Other DOX delivery techniques based on different interactions were also fascinating, such as the Schiff‐based reaction 113 between DOX and l ‐lysine, which contributed to the pH sensitivity (accelerated DOX release in pH 5.5), and the liposomal doxorubicin (DOX‐Lip) embedded PLGA‐PEG‐PLGA hydrogel with an improved stability and prolonged therapeutic effect, 114 which also emphasized the suitable role of liposome serving as a delivery dosage form.…”