title: Enhanced drug loading on magnetic nanoparticles by layer-by-layer assembly using drug conjugates: blood compatibility evaluation and targeted drug delivery in cancer cells.
abstract: Drug targeting using magnetic nanoparticles (MNPs) under the action of an external magnetic field constitutes an important mode of drug delivery. Low cargo capacity, particularly in hydrophobic drugs, is one limitation shown by MNPs. This article describes a simple strategy to enhance the drug-loading capacity of MNPs. The approach was to use polymer-drug conjugates to modify MNPs by layer-by-layer assembly (LbL). Curcumin (CUR) has shown remarkably high cytotoxicity toward various cancer cell lines. However, the drug shows low anticancer activity in vivo because of its reduced systemic bioavailability acquired from its poor aqueous solubility and instability. To address this issue, we synthesized cationic and anionic CUR conjugates by anchoring CUR onto poly(vinylpyrroidone) (PVP-Cur) and onto hyaluronic acid (HA-Cur). We used these oppositely charged conjugates to modify MNPs by layer-by-layer (LbL) assembly. Six double layers of curcumin conjugates were constructed on positively charged amino-terminated magnetic nanoparticles, TMSPEDA@MNPs. Finally, HA was coated onto the outer surface to form HA (HA-Cur/PVP-Cur)(6)@MNPs. Cellular viability studies showed the dose-dependent antiproliferative effect of HA (HA-Cur/PVP-Cur)(6)@MNPs in two cancer cell lines (glioma cells and Caco-2 cells). HA (HA-Cur/PVP-Cur)(6)@MNPs exhibited more cytotoxicity than did free curcumin, which was attributed to the enhanced solubility along with better absorption via hyaluronic acid receptor-mediated endocytosis. Flow cytometry showed enhanced intake of the modified MNPs by cells. Confocal microscope images also confirmed the uptake of HA (HA-Cur/PVP-Cur)(6)@MNPs with greater efficacy. Thus, the strategy that we adopted here appears to have substantial potential in carrying enhanced payloads of hydrophobic drugs to specified targets.
authors: Laboratory for Polymer Analysis, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Poojapura Trivandrum 695012, India.
authors: S
authors: S
authors: Manju
authors: K
authors: K
authors: Sreenivasan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008280:Magnetics; D008567:Membranes, Artificial; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D008567:Membranes, Artificial; D003474:Curcumin