Preparation and evaluation of SiO2-deposited stearic acid-g-chitosan nanoparticles for doxorubicin delivery

Abstract

Purpose: Both polymer micelles and mesoporous silica nanoparticles have been widely researched as vectors for small molecular insoluble drugs. To combine the advantages of copolymers and silica, studies on the preparation of copolymer-silica composites and cellular evaluation were carried out. Methods: First, a stearic acid-g-chitosan (CS-SA) copolymer was synthesized through a coupling reaction, and then silicone oxide (SiO 2 )-deposited doxorubicin (DOX)-loaded stearic acid-g-chitosan (CS-SA/SiO 2 /DOX) nanoparticles were prepared through the sol-gel reaction. Physical and chemical properties such as particle size, zeta potential, and morphologies were examined, and small-angle X-ray scattering (SAXS) analysis was employed to identify the mesoporous structures of the generated nanoparticles. Cellular uptake and cytotoxicity studies were also conducted. Results: CS-SA/SiO 2 /DOX nanoparticles with different amounts of SiO 2 deposited were obtained, and SAXS studies showed that mesoporous structures existed in the CS-SA/SiO 2 / DOX nanoparticles. The mesoporous size of middle-ratio and high-ratio deposited CS-SA/SiO 2 / DOX nanoparticles were 4-5 nm and 8-10 nm, respectively. Based on transmission electron microscopy images of CS-SA/SiO 2 /DOX nanoparticles, dark rings around the nanoparticles could be observed in contrast with CS-SA/DOX micelles. Furthermore, CS-SA/SiO 2 /DOX nanoparticles exhibited faster release behavior in vitro than CS-SA/DOX micelles; cellular uptake research in A549 indicated that the CS-SA/SiO 2 /DOX nanoparticles were taken up by A549 cells more rapidly, and that CS-SA/SiO 2 /DOX nanoparticles entered the cell more easily when the amount of SiO 2 was higher. IC 50 values of CS-SA/DOX micelles, CS-SA/SiO 2 /DOX-4, CS-SA/ SiO 2 /DOX-8, and CS-SA/SiO 2 /DOX-16 nanoparticles against A549 cells measured using the MTT assay were 1.69, 0.93, 0.32, and 0.12 µg/mL, respectively. Conclusion: SiO 2 -deposited stearic acid-g-chitosan organic-inorganic composites show promise as nanocarriers for hydrophobic drugs such as DOX.

Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent

“…17 For instance, pore size distribution can be changed to alter release rate of encapsulated drug. 18 Sol-gel technology is also cost effective, biocompatible, and nontoxic. 17 Our platform has been employed to encapsulate agents ranging from nitric oxide for infection and wound healing 15,19 to amphotericin B for fungal burn wound infections 20 to sildenafil for erectile dysfunction.…”

Silica‐based organic‐inorganic hybrid nanoparticles and nanoconjugates for improved anticancer drug delivery

“…The change in size, shape, charge and stiffness of the materials to enhance tissue accumulation, adhesion, cellular uptake of nanoparticles and drugs are part of the strategy [23]. The results showed that the nanoparticles have a more rapid drug release rate in vitro than the micelles and they could easily penetrate into the cells due to higher specific surface area obtained by their mesoporous structure [25] which, not only serve as unique drug reservoirs but also have a part in multiphasic release systems. Some anticancer drugs like camptothecin and doxorubicin (DOX) are effective in chemotherapy but the applications in humans were limited due to the poor water solubility of the drug.…”

“…The polyethyleneimine-polyethylene glycol (PEI-PEG) decoration on the surface of the nanoparticles was reported to decrease RES uptake and resulted in the retention of about 8% of the administered particle dose at tumor site [28]. The surface modifications of recent organic-inorganic silica hybrids with polymers are mostly based on PEG [27], PEI [28], PVP [29], chitosan [25] and poly-L-lactic acid (PLLA) [26] for drug targeting to cancer cell (Table 1). In one of the studies, PVP was used as a protecting polymer adsorbed on the surface of silica microspheres and NaOH was employed as an etching agent.…”

“…For instance, silicone oxide-deposited DOX-loaded stearic acid-grafted-chitosan nanoparticles were compared with stearic acid-g-chitosan polymeric micelles. The results showed that the nanoparticles have a more rapid drug release rate in vitro than the micelles and they could easily penetrate into the cells due to higher specific surface area obtained by their mesoporous structure [25] which, not only serve as unique drug reservoirs but also have a part in multiphasic release systems. In another study, drug delivery system using DOX loaded mesoporous silica nanoparticle composite nanofibers was fabricated which can release anti-tumor drugs in two phases (burst release in the early stage and sustained release at a later stage) to reduce local recurrence of breast-conserving therapy [26].…”

Study of novel nanoparticle transport and drug release for cancer treatment.

“…Drugs such as bortezomib, the first clinically approved proteasome inhibitor, experienced limited efficacy due to its poor water-solubility and stability. Using and cytotoxicity of doxorubicin-loaded stearic acid-g-chitosan nanoparticles in A549 cells demonstrating faster cellular uptake with increased silica ratio [255]. Despite the advantages of ceramic nanoparticles in drug delivery and cancer therapy, questions have been raised about the potential toxic effects.…”