Synthesis and characterization of dual light/temperature-responsive supramolecular injectable hydrogel based on host-guest interaction between azobenzene and starch-grafted ß-cyclodextrin: Melanoma therapy with paclitaxel.

Injectable stimuli-responsive hydrogels could offer an opportunity for local administration at the tumor site and a sustained drug release. In this paper, a copolymer of azobenzene derivative and N-isopropyl acrylamide (NIPAM) was synthesized, which are performed as light- and thermo-sensitive parts, respectively. The DAS@SCD/NIPAZO hydrogel was prepared upon the establishment of host-guest interactions between the hydrophobic core of CD and azobenzene moiety. The LCST of the synthesized copolymer was modified from 31.3 °C to 36.5 °C by the incorporation of the hydrophilic host moieties of the modified starch into the NIPAM copolymer structure. The LCST-based property of the hydrogel made it syringable in low temperatures and switch to a gel state after local injection. The drug release profile of the hydrogel was explored in four different conditions involving two distinct temperatures combined with two different light wavelengths to examine the light- and thermo-sensitivity of the hydrogel. Moreover, a Paclitaxel-loaded hydrogel was prepared to study the in vitro efficiency of the sample and was investigated by MTT assay against the cancerous fibroblastic cells (A-431), which revealed a sharp decline in cell viability under 365 nm light irradiation; furthermore, to evaluate the in vivo effects of the PTX-loaded hydrogel, histological studies based on staining techniques were carried out.

Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer.

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.