Andri Hardiansyah

Novel pH-sensitive drug carriers of carboxymethyl-hexanoyl chitosan (Chitosonic® Acid) modified liposomes

In this study, novel hybrid nanocarriers composed of carboxymethyl-hexanoyl chitosan (Chitosonic® Acid, CA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-liposomes were developed. CA was immobilized onto the DSPE-liposomes by EDC/NHS reaction using the carboxyl group of CA and the amino group of DSPE. The characteristics of the resultant CA-modified liposomes were evaluated by transmission electron microscopy, dynamic light scattering, zeta potential, FTIR spectroscopy, X-ray photoelectron spectroscopy, and contact angle measurement. The results show that the particle size and surface charge of the CA-modified liposomes varied with the concentration of CA, and exhibited pH-sensitive behavior. In vitro drug release studies demonstrated the sustained release behavior of the doxorubicin in the CA-modified liposomes, related to the rapid release in the free doxorubicin. Interestingly, the doxorubicin release rate from CA-modified liposomes was lower at higher pH values (pH 7.4) than at lower pH values (pH 4), indicating that the drug carrier displayed pH-sensitive released behavior. Furthermore, CA-modified liposomes exhibited no cytotoxicity toward the fibroblast cells (L-929 cells), suggesting an excellent biocompatibility. Fluorescence and confocal microscopy images showed good cellular internalization of the CA-modified liposomes into the cellular compartment. These results confirm that the novel CA-modified liposomes could respond to pH environment, which is promising for drug controlled release applications, especially in the field of cancer cell therapy (lower pH environments).

Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy

Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy.

Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release

In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe3O4-NH2, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release.

Basic Properties of PMMA Reinforced Using Ceramics Particles of ZrO2-Al2O3-SiO2 Coated with Two Types of Coupling Agents

In this study, novel composites materials composed of polymethyl methacrylate (PMMA) reinforced ZrO2-Al2O3-SiO2 filler system were developed. Zirconia-alumina-silica filler system were synthesized through sol-gel technique. Chitosan and trimethoxypropilsilane (TMPS) were used to modify the composites system. The resulting composites material were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD) and hardness test. SEM images displayed the composites particles in nanometer size with minor agglomeration. The XRD results revealed the presence of cubic and tetragonal phase of zirconia and also monoclinic silica phases in the composites system. These crystallographic characteristic could affect the mechanical properties of the composites. The hardness value for un-modified composites was 15.27 ± 0.25 VHN and for TMPS 19.43 ± 1.89 VHN and chitosan modification 18.75 ± 2.05 VHN, respectively. Therefore, these novel composites materials composed of PMMA reinforced filler system of zirconia-alumina-silica would provide the potential to apply in dental technology.

Nanohybrid structure analysis and biomolecule release behavior of polysaccharide-CDHA drug carriers

Nanoscaled polymer composites were prepared from polysaccharide chitosan (CS) and Ca-deficient hydroxyapatite (CDHA). CS-CDHA nanocomposites were synthesized by in situ precipitation at pH 9, and the CS-CDHA carriers were then fabricated by ionic cross-linking methods using tripolyphosphate and chemical cross-linking methods by glutaraldehyde and genipin. Certain biomolecules such as vitamin B12, cytochrome c, and bovine serum albumin were loaded into the CS-CDHA carriers, and their release behaviors were investigated. Furthermore, these CS-CDHA carriers were examined by transmission electron microscopy, electron spectroscopy for chemical analysis, and X-ray diffraction. The release behavior of the biomolecules was controlled by the CS/CDHA ratios and cross-linked agents. By increasing the concentration of CS and the concentration of the cross-linking agents, cross-linking within carriers increases, and the release rate of the biomolecules is decreased. Moreover, the release rate of the biomolecules from the CS-CDHA carriers at pH 4 was higher than that at pH 10, displaying a pH-sensitive behavior. Therefore, these CS-CDHA hydrogel beads may be useful for intelligent drug release and accelerate bone reconstruction.

Synthesis and Characterization of MgPSZ-PMMA Composite by Sol-Gel Modification and Direct Foaming Technique Using Egg Whites

This study prepared Magnesium-Partially Stabilized Zirconia (Mg-PSZ) filler synthesis and direct foaming technique using egg whites, and impregnated by PMMA. The results were evaluated systematically by X-ray diffraction (XRD), Scanning Electron Microscope (SEM), and Transmission Electron Microscope (TEM). XRD results denote that the powder sample of MgPSZ was successfully formed with various crystal size of tetragonal and monoclinic phase. SEM and TEM observations revealed that nanoparticles MgPSZ were in spherical and long rounded shapes. Furthermore, SEM observation revealed that the direct foaming method were also successful in the formation of porous structures which favourable for impregnation process by PMMA. The use of egg whites as a polymer precursor in both methods demonstrates that porous specimens contained nanosized, predominantly tetragonal, Mg-PSZ powders were successfully synthesized. This shall yield an interesting prospect towards cheap, reliable, and biocompatible product to resemble the modulus elasticity of dentin.