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Drug uptake by polymer was modeled using a molecular dynamics (MD) simulation technique. Three drugs--doxorubicin (water soluble), silymarin (sparingly water soluble) and gliclazide (water insoluble)--and six polymers with varied functional groups--alginic acid, sodium alginate, chitosan, Gantrez AN119 (methyl-vinyl-ether-co-malic acid based), Eudragit L100 and Eudragit RSPO (both acrylic acid based)--were selected for the study. The structures were modeled and minimized using molecular mechanics force field (MM+). MD simulation (Gromacs-forcefield, 300 ps, 300 K) of the drug in the vicinity of the polymer molecule in the presence of water molecules was performed, and the interaction energy (IE) between them was calculated. This energy was evaluated with respect to electric-dipole, van der Waals and hydrogen bond forces. A good linear correlation was observed between IE and our own previous data on drug uptake(*) [R² = 0.65, R²adj = 0:65; R²pre = 0:56 and a F ratio of 30.25, P < 0.001; Devarajan et al. (2005) J Biomed Nanotechnol 1:1-9]. Maximum drug uptake by the polymeric nanoparticles (NP) was achieved in water as the solvent environment. Hydrophilic interaction between NP and water was inversely correlated with drug uptake. The MD simulation method provides a reasonable approximation of drug uptake that will be useful in developing polymer-based drug delivery systems.

Nanoparticles have widely been studied in drug delivery research for targeting and controlled release. The aim of this article is application of nanoparticles as an inhalable agent for treatment of lung cancer. To deposit effectively deep the particles in the lungs, the PLGA nanoparticles loaded with the anticancer drug 6-{[2-(dimethylamino)ethyl]amino}-3-hydroxyl-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103) were prepared in the form of nanocomposite particles. The nanocomposite particles consist of the complex of drug-loaded nanoparticles and excipients. In this study, the anticancer effects of the nanocomposite particles against the lung cancer cell line A549. Also, the concentration of TAS-103 in blood and lungs were determined after administration of the nanocomposite particles by inhalation to rats. TAS-103-loaded PLGA nanoparticles were prepared with 5% and 10% of loading ratio by spray drying method with trehalose as an excipient. The 5% drug-loaded nanocomposite particles were more suitable for inhalable agent because of the sustained release of TAS-103 and higher FPF value. Cytotoxicity of nanocomposite particles against A549 cells was higher than that of free drug. When the nanocomposite particles were administered in rats by inhalation, drug concentration in lung was much higher than that in plasma. Furthermore, drug concentration in lungs administered by inhalation of nanocomposite particles was much higher than that after intravenous administration of free drug. From these results, the nanocomposite particle systems could be promising for treatment of lung cancer.

The aim of this study was to formulate and optimize gliclazide-loaded Eudragit nanoparticles (Eudragit L100 and Eudragit RS) as a sustained release carrier with enhanced efficacy. Eudragit L 100 nanoparticles (ELNP) were prepared by controlled precipitation method whereas Eudragit RSPO nanoparticles (ERSNP) were prepared by solvent evaporation method. The influence of various formulation factors (stirring speed, drug:polymer ratio, homogenization, and addition of surfactants) on particle size, drug loading, and encapsulation efficiency were investigated. The developed Eudragit nanoparticles (L100 and RS) showed high drug loading and encapsulation efficiencies with nanosize. Mean particle size altered by changing the drug:polymer ratio and stirring speed. Addition of surfactants showed a promise to increase drug loading, encapsulation efficiency, and decreased particle size of ELNP as well as ERSNP. Dissolution study revealed sustained release of gliclazide from Eudragit L100 as well as Eudragit RSPO NP. SEM study revealed spherical morphology of the developed Eudragit (L100 and RS) NP. FT-IR and DSC studies showed no interaction of gliclazide with polymers. Stability studies revealed that the gliclazide-loaded nanoparticles were stable at the end of 6 months. Developed Eudragit NPs revealed a decreased t(min) (ELNP), and enhanced bioavailability and sustained activity (ELNP and ERSNP) and hence superior activity as compared to plain gliclazide in streptozotocin induced diabetic rat model and glucose-loaded diabetic rat model. The developed Eudragit (L100 and RSPO) NP could reduce dose frequency, decrease side effects, and improve patient compliance.