1. The targeted blood-brain barrier (BBB) delivery of antibiotics was carried out using biologically active polymer core/shell nanoparticles (called micelles), self-assembled and fabricated from TAT-poly(ethylene glycol) (PEG)-b-cholesterol (TAT-PEG-b-Chol). The nanoparticles were efficiently loaded with ciprofloxacin as a model antibiotic by employing membrane dialysis method. The initial loading of ciprofloxacin and fabrication temperature determined the actual level of loading. The identification of the blank and ciprofloxacin-loaded nanoparticles was carried out using dynamic light scattering and SEM. The average size of nanoparticles was lower than 200 nm and were spherical in nature.
The nanoparticles with TAT on the surfaces showed greater uptake by human brain endothelial cells than those without TAT. The nanoparticles with TAT were vital in their ability to cross the blood-brain barrier (BBB), and locate around the cell nucleus of neurons. Future opportunities may lie in these nanoparticles to act as a carrier for delivering antibiotics across the BBB for brain infection treatment2.
The loading and release of 5-Fluorouracil and Ftorafur using carbonyl iron/poly(butylcyanoacrylate) core/shell particlesand procedures for enhancing them were studied. The composite particles were synthesizedusing the anionic polymerizationprocedure, used to obtain drug-delivering poly(alkylcyanoacrylate) nanoparticles,except forcarbonyl iron suspension as the polymerization medium. Spectrophotometric and electrophoretic measurements revealed the effects of two mechanisms of drug incorporation (entrapment in the polymeric network and surface adsorption) on drug loading and release profiles. The drug release evaluations were performed at the ascertained optimum loading conditions. The drug concentration and pH were the two main determining factors among others that affected the drug loading. The drug adsorbed on the surface released rapidly (nearly 100% in 1h), whereas the drug incorporated in the polymer matrix needed 10 to 20h to be fully released. Thus, the release profile was biphasic for both the drugs.
The pH of the release medium, the type of drug incorporation, and the amount of drug loaded were found to be the main factors governing the kinetics of drug release form core/shell particles. Comparison between 5-FU and Ftorafur was made indicating that the former drug is less absorbed and released at a faster rate. The reason to this can be its larger hydrophilicity as compared to Ftorafur.3.
Alkaline coprecipitation of ferric and ferrous ions in the presence of a triblock copolymer, methoxy poly(ethylene glycol)-block-poly(methacrylic acid)-block-poly(glycerol monomethacrylate) (denoted MPEG-b-PMAA-b-PGMA), in aqueous solution, was employed to prepare a multifunctional nanocarrier with multilayer core–shell architecture. The DLS revealed the average diameter of the nanocarrier in aqueous solution to be 23 nm.The PGMA block of the triblock copolymer is attached on the core of the nanocarrier, which is a superparamagnetic Fe3O4 nanoparticlewith an average diameter of 7 nm.
PGM block was used to tightly attach MPEG-b-PMAA-b-PGMA onto the surface of the Fe3O4 nanoparticle. The inner shell and the outermost shell are formed by the PMAA block and MPEG block, respectively.The biocompatible outermost MPEG shell resulted in low cytotoxicity of the nanocarrier. Protonated ADR (pKa=8.2) was adsorbed onto PMAA (pKa=5.6) chains, in which carboxylic acid groups were deprotonated to form carboxylate anions.
The combined action of ionic bonding and hydrophobic interaction at pH 7.4, loaded the anticancer agent adriamycin (ADR) in to the nanocarrier as a model drug with an amine group and a hydrophobic moiety. The hydrophobic interaction was a result of the hydrophobic main chain of PMAA and the hydrophobic microenvironment created by MPEG.
The loading capacity was significantly enhanced by the synergistic effect between the ionic bond and the hydrophobic interaction. The hydrophobic interaction alone is very weak due to the relatively hydrophilic character of nanocarrier, therefore, the ADR is released because of breakage of ionic bond between the career and ADR because of protonation of polycarboxylate anions of PMAA (pKa = 5.6) at endosomal/lysosomal acidic pH (
