Poly(amidoamine) Dendrimer/Camptothecin Complex: From Synthesis to In Vitro Cancer Cell Line Studies.

Camptothecin (CPT), an alkaloid with potent anticancer activity, is still not used in clinical practice due to its high hydrophobicity, toxicity, and poor active-form stability. To address these shortcomings, our research focuses on the encapsulation of this drug in the poly(amidoamine) (PAMAM) dendrimer macromolecule. The PAMAM dendrimer/CPT complex was synthesized and thoroughly characterized. The in vitro drug release study revealed that the drug was released in a slow and controlled manner in acidic and physiological conditions and that more than 80% of the drug was released after 168 h of incubation. Furthermore, it was demonstrated that CPT was released with first-order kinetics and non-Fickian transport. The studies on the hemolytic activity of the synthesized complex indicated that it is hemocompatible for potential intravenous administration at a concentration ≤ 5 µg/mL. Additionally, the developed product was shown to reduce the viability of non-small-cell lung cancer cells (A549) in a concentration- and time-dependent manner, and cancer cells were more susceptible to the complex than normal fibroblasts. Lastly, molecular modeling studies revealed that the lactone or carboxylic forms of CPT had a significant impact on the shape and stability of the complex and that its formation with the lactone form of CPT was more energetically favorable for each subsequent molecule than the carboxylic form. The report represents a systematic and structured approach to develop a PAMAM dendrimer/CPT complex that can be used as an effective drug delivery system (DDS) for the potential treatment of non-small-cell lung cancer.

A Comprehensive Investigation of the Structural, Thermal, and Biological Properties of Fully Randomized Biomedical Polyesters Synthesized with a Nontoxic Bismuth(III) Catalyst.

Aliphatic polyesters are the most common type of biodegradable synthetic polymer used in many pharmaceutical applications nowadays. This report describes the ring-opening polymerization (ROP) of l-lactide (L-LA), ε-caprolactone (CL) and glycolide (Gly) in the presence of a simple, inexpensive and convenient PEG200-BiOct3 catalytic system. The chemical structures of the obtained copolymers were characterized by 1H- or 13C-NMR. GPC was used to estimate the average molecular weight of the resulting polyesters, whereas TGA and DSC were employed to determine the thermal properties of polymeric products. The effects of temperature, reaction time, and catalyst content on the polymerization process were investigated. Importantly, the obtained polyesters were not cyto- or genotoxic, which is significant in terms of the potential for medical applications (e.g., for drug delivery systems). As a result of transesterification, the copolymers obtained had a random distribution of comonomer units along the polymer chain. The thermal analysis indicated an amorphous nature of poly(l-lactide-co-ε-caprolactone) (PLACL) and a low degree of crystallinity of poly(ε-caprolactone-co-glycolide) (PCLGA, Xc = 15.1%), in accordance with the microstructures with random distributions and short sequences of comonomer units (l = 1.02-2.82). Significant differences in reactivity were observed among comonomers, confirming preferential ring opening of L-LA during the copolymerization process.

Sterilization process of polyester based anticancer-drug delivery systems.

Recently, growing interest in biodegradable polyesters as drug carriers in the development of innovative anticancer drug delivery systems (DDSs) has been observed. These compounds are thermally unstable, and are therefore, particularly demanding due to the limited number of available sterilization techniques. Furthermore, the DDSs sterilization process is often limited to aseptic filtration. Ensuring aseptic production is very demanding and costly, and it is therefore necessary to work on the application of new sterilization methods. In view of this, this review presents the current state of knowledge regarding the radiation sterilization process of some anticancer drugs as well biodegradable polyester carriers (such as polylactide, polyglycolide, poly(ε-caprolactone), poly(trimethylene carbonate) and co- or terpolymers of lactide, glycolide, ε-caprolactone and trimethylene carbonate). The structural changes in anticancer DDSs under the influence of ionizing radiation and the potential degradation mechanisms of both, polyester carriers and cytostatics during the sterilization process of ionizing radiation as well as their effects on the microstructure and properties of DDSs have been discussed in this paper.

On the driving forces for complexation of methyl orange with polycations.

HYPOTHESIS: Complexation between Methyl orange and polycations involves multiple interactions dictated by molecular structure, composition (D/P), pH and ionic strength. The effect of ionic strength is considered a generic effect. By step-wise construction of complexes, we expect to gain insight in the nature of interactions and whether displacement by competing ions is a generic effect. EXPERIMENTS: We step-wise constructed complexes of methyl orange with two model polycations, whilst recording visible light spectra, size and electrophoretic mobility in buffered solution. MO organization was derived from discrete spectral changes, whereas complexes were described in terms of size and zeta-potential data. Spectral data were used to study the effect of competing ions, both potassium halides and polyanions, using a manual titration method. FINDINGS: Spectral and size data reveal a complex stoichiometry of D/P=2.2 and 4.6 for poly(ethylenimine hydrochloride)(PEI) and poly(di allyldimethyl amine hydrochloride) PDADMAC, respectively. Contrary to PEI-MO, the formation of PDADMAC-MO complexes is driven by hydrophobic rather than electrostatic interactions. Organization of PDADMAC-MO complexes also shows a strong dependency on the order of construction and polycation concentration. Displacement of MO by halides shows no effect of ion size for PEI, whereas Hofmeister series ordering was found for PDADMAC. The displacement by polyanions is shown to be charge-stoichiometric.

[The influence of nutritional intervention on resting energy expenditure in obese adolescents aged 15-18 years]. / Wplyw interwencji zywieniowej na spoczynkowy wydatek energetyczny u otylej mlodziezy w wieku 15-18 lat.

The aim of this research was to assess the influence of dietary intervention on weight loss and resting energy expenditure (REE) in 20 obese and overweight adolescents (BMI = 29 +/- 3,8 kg/m2) aged 15-18 years. Nutritional habits and nutritional status were estimated before and after the introduction of low-calorie diet. Measurements of REE were carried out by indirect calorimetry in a respiratory chamber Nutritional intervention had a significant influence in decreasing body weight (from 85 +/- 14.3 kg to 82.5 +/- 12.8 kg), BMI and fat mass. Muscle mass was found to be significantly elevated (p < 0.050). REE did not decline significantly due to nutritional intervention (p > 0.05; p = 0.84).