Natural Salep/PEGylated Chitosan Double Layer toward a More Sustainable pH-Responsive Magnetite Nanocarrier for Targeted Delivery of DOX and Hyperthermia Application

Abstract

Two pH-responsive polysaccharide-based magnetite nanocarriers have been developed from modified salep and PEGylated chitosan decorated onto the surface of magnetite nanoparticles for active loading and targeted delivery of doxorubicin. The first nanocarrier was formed via imine bond formation and electrostatic hydrogen bonding interactions between dialdehyde salep-modified magnetite nanoparticles and DOX in a one-layered nanocarrier fashion. Subsequently, PEGylated chitosan was used as a second layer on the surface of the first nanocarrier, mainly by the same interactions, producing a double-layered polysaccharide-based nanocarrier. In vitro release studies indicated that the use of PEGylated chitosan as the second shell provides more control on the rate and amount of DOX release and makes double-layered nanocarrier more pH-sensitive. Magnetic heating capacity of double-layered nanocarrier was investigated and release profile under AMF (42 °C, magnetically induced) showed a good improvement in the time and amount of DOX release. In vitro MTT assays depicted that the DOX-loaded double-layered nanocarrier produces a large cytotoxic response to HeLa cells, which is comparable with free DOX in higher concentration. DOX-free double-layered nanocarrier also exhibited low cytotoxicity against normal cells, an indication of their excellent biocompatibility. Application of AMF also showed a large effect on the cytotoxicity of the nanocarrier rather than without AMF condition. Investigation on cellular uptake of nanocarrier revealed the high targeting ability of nanocarrier toward HeLa cells, especially in the presence of AMF. Blood compatibility investigations indicated that hemolysis of RBCs and coagulation times fall into the normal range for blood in the presence of DOX-free and DOX-loaded double-layered nanocarrier.

Herceptin-Conjugated DOX-Fe3O4/P(NIPAM-AA-MAPEG) Nanogel System for HER2-Targeted Breast Cancer Treatment and Magnetic Resonance Imaging

“…Many related studies of DOX delivery systems provided the FTIR evidence of DOX conjugation to the carrier . The peaks at 1050, 1104, and 1255 cm –1 could be ascribed to the presence of DOX, − indicating that DOX was loaded into MNL-1. The peak intensity at 1087 and 1050 cm –1 increased for HER-DOX-MNL-1, suggesting that HER was successfully conjugated onto MNL-1.…”

Ruthenium (III)–Indigo Complex Loaded on the Salep Hydrogel as an Anti-inflammatory and Antioxidant Nanocomposite

“…10,42 Salep-based nanocarriers were used for drug delivery in many investigations. For example, Zohreh et al 37 designed a magnetic pH-responsive nanocarrier using modified salep and PEGylate chitosan for doxorubicin (DOX) delivery and hyperthermia.…”

“…Although ruthenium complexes have substantial therapeutic effects, they have limits for clinical usage, such as dose-dependent side effects and a short circulation time. Hence, use of nanosystems for drug delivery is suggested to manage these issues. , Hydrogel nanocarriers are stable systems with high biodegradability, biocompatibility, and low toxicity proposed to carry hydrophobic herbs and drugs. , Among the known hydrogels, natural ones such as chitosan, tragacanth, Arabic gum, and salep are preferred for therapeutic purposes. − Salep is a hydrogel obtained from the tubers of the Orchis chusua D. Don plant and composed of glucomannan, starch, and mineral substances (Scheme ). , Furthermore, salep has been used as a herbal medicine for many years to ameliorate pain, inflammations, arthritis, eczema, asthma, bone ruptures, and wounds. , Salep-based nanocarriers were used for drug delivery in many investigations.…”

“… , Furthermore, salep has been used as a herbal medicine for many years to ameliorate pain, inflammations, arthritis, eczema, asthma, bone ruptures, and wounds. , Salep-based nanocarriers were used for drug delivery in many investigations. For example, Zohreh et al designed a magnetic pH-responsive nanocarrier using modified salep and PEGylate chitosan for doxorubicin (DOX) delivery and hyperthermia. The results showed that the prepared DOX-free nanocarrier is nontoxic against normal cells, and the DOX-loaded nanocarrier has high toxicity to Hela cancer cells.…”

Vitamin-H Channeled Self-Therapeutic P-gp Inhibitor Curcumin-Derived Nanomicelles for Targeting the Tumor Milieu by pH- and Enzyme-Triggered Hierarchical Disassembly

“…Nanocarriers with targeting abilities can undergo by accelerated tumor homing because of the enhanced permeability and retention (EPR) effect. Although nanomedicines have shown promising potential in cancer management, various issues like encountering sequential drug delivery barriers, insufficient blood circulation process, in vivo rapid drug leakage, and limited tumor penetration capability still remain as bottleneck for an effective therapy. , A facile strategy to counter this paradox can be the rational design of biocompatible nanocarriers , undergoing self-adaptive transformations in terms of size, selectively in the tumor milieu in response to pH, enzyme, glutathione, etc., to release the cargo . A structural metamorphosis in the material microstructure only in the tumor microenvironment can be attained by introduction of acid-labile ortho ester, hydrazone, cis-aconitic amide, and acetal linkages in it.…”