Incorporation of camptothecin into N-phthaloyl chitosan-g-mPEG self-assembly micellar system.

The capability of N-phthaloylchitosan-grafted poly (ethylene glycol) methyl ether (mPEG)(PLC-g-mPEG) to enhance the aqueous solubility and stability of the lactone form of camptothecin (CPT) was investigated. PLC-g-mPEG formed a core-shell micellar structure after dialysis of the polymer solutions in dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) against water, with a critical micelle concentration (CMC) of 28 microg/ml. CPT was loaded into the inner core of the micelles by dialysis method. The results showed an increase in the CPT-loading amount with an increasing concentration of CPT. The stability of drug-loaded micelles was studied by gel-permeation chromatography (GPC), and their in vitro release behaviors were analyzed. Release of CPT from the micelles was sustained. When compared to the unprotected CPT, CPT-loaded PLC-g-mPEG micelles were able to prevent the hydrolysis of the lactone group of the drug. The kinetics of the CPT hydrolysis in human serum albumin (HSA) and fetal bovine serum (FBS) were pseudo-first order. The hydrolysis rate constants for CPT and CPT-loaded PLC-g-mPEG micelles in phosphate-buffered saline (PBS) pH 7.4, were 7.4 x 10(-3) min(-1) and 9.1 x 10(-3) h(-1), parallel to an increase in half-life of CPT from 94 min to 76.15 h, respectively.     

Incorporation of Benzoxazine Pendants in Polymer Chains: A Simple Approach to Add‐Up Multi‐Responsive Functions

External stimuli responsive polymers can be derived from the functional side group in copolymers. Benzoxazine dimer is a good candidate for expressing multi‐responsive properties based on the type of phenol in combination with its metal complexation. The present work proposes a vinyl monomer containing a benzoxazine pendant, which contains an azo group as the functional monomer. The copolymerization with methylmethacrylate (MMA) via atom transfer radical polymerization leads to a block copolymer, specifically, PA‐Azo‐C3‐b‐PMMA, which forms uniform nanoparticles. The ring opening of benzoxazine monomer results in dimer pendants. The copolymer obtained, PA‐Azo‐C3‐b‐PMMA, shows multi‐responsive functions in terms of metal ion complexation, and UV responsiveness through the dimer pendants and azobenzene groups. The UV exposure results in loss of uniformity of the nanoparticles as well as a decrease in size. This work demonstrates the role of benzoxazine pendants in developing PMMA copolymer showing external stimuli responsive functions.     

N-Phthaloylchitosan-g-mPEG design for all-trans retinoic acid-loaded polymeric micelles

The amphiphilic grafted copolymer N-phthaloylchitosan-grafted poly(ethylene glycol) methyl ether (PLC-g-mPEG) was synthesized using chitosan with four different degrees of deacetylations (DD) (80, 85, 90 and 95%). All-trans retinoic acid (ATRA) was incorporated into PLC-g-mPEG by dialysis method in an attempt to optimize carriers for ATRA delivery. Morphological investigation by transmission electron microscopy (TEM) showed that the particles had round and uniform shapes. The particle sizes of ATRA incorporated into micelles were about 80–160 nm depending on the initial drug-loaded and %DD of chitosan. Physicochemical properties of ATRA-loaded polymeric micelles were also investigated. It was found that %DD of chitosan, which corresponded to the N-phthaloyl groups in the inner core of the micelles, was a key factor in controlling the incorporation efficiency, stability of the drug-loaded micelles and drug release behavior. As the %DD increased, the incorporation efficiency and ATRA-loaded micelles stability increased. The sustained release profiles were also obtained at high %DD (90 and 95%). When compared to the unprotected ATRA, ATRA loaded in PLC-g-mPEG micelles was efficiently protected from photodegradation. This result suggested that loading of ATRA in micelles improved the chemical stability of ATRA.     

Epithelial sodium channel allele T594M is not associated with blood pressure or blood pressure response to amiloride

The T594M allele of the epithelial sodium channel beta-subunit has been proposed as a gain-of-function mutation leading to salt-sensitive hypertension in blacks that is particularly responsive to the specific sodium channel antagonist amiloride. However, the positive associations derive from small convenience samples, and the amiloride challenge study lacked a control group. We determined whether the T594M allele was associated with hypertension and blood pressure (BP) response to amiloride in 2 well-characterized random population samples including 3137 Dallas County subjects and 1666 Jamaican blacks. In multivariate models, the T594M allele was not predictive of systolic BP (adjusted odds ratio for hypertension 1.1; 95% confidence interval, 0.7 to 1.8). Amiloride treatment did not lower the BP of 6 T594M heterozygotes significantly more than in 22 control subjects (P=0.8). We conclude that the T594M allele does not contribute significantly to BP in blacks and does not predict a significantly superior response to amiloride therapy.