Paul O. Stanescu

A2BA2 Block Copolymers of Poly(N-isopropylacrylamide) (A) and Poly(ethylene glycol) (B): Synthesis and Thermal Gelation Properties of Aqueous Solutions

A2BA2 block copolymers of poly(N-isopropylacrylamide) (A, PNIPAM) and poly(ethylene glycol) (B, PEG) were synthesized by SET-LRP for the first time. The 1H-NMR and GPC analyses showed that the block copolymers prepared had in average 3.5–3.8 PNIPAM arms/macromolecule and low polydispersities (Mw/Mn=1.25–1.35). The thermogelation behavior of their 20 wt% aqueous solutions was investigated by DSC, dynamic rheometry and the tube inversion method as a function of the molecular weight of both PEG block and PNIPAM arms. The results showed that both phase transition temperature, as determined by DSC, and gelation temperature, determined by the tube inversion method, increased with the PEG block length and decreased with the MW of the PNIPAM arms, while the forming gels were more stable for longer PEG chains. By comparing the thermoresponsive properties of the H-shaped block copolymers synthesized with those of some linear PNIPAM-PEG-PNIPAM triblock copolymers of similar molecular weights of both PNIPAM side blocks and PEG middle chain, almost identical results were obtained, indicating practically no influence of the shape of the PNIPAM blocks from this point of view.

In Vitro Studies of Bacterial Cellulose and Magnetic NanoparticlesSmart Nanocomposites for Efficient Chronic Wounds Healing

The quality of life of patients with chronic wounds can be extremely poor and, therefore, over the past decades, great efforts have been made to develop efficient strategies to improve the healing process and the social impact associated with these conditions. Cell based therapy, as a modern tissue engineering strategy, involves the design of 3D cell-scaffold bioconstructs obtained by preseeding drug loaded scaffolds with undifferentiated cells in order to achieve in situ functional de novo tissue. This paper reports on the development of bionanocomposites based on bacterial cellulose and magnetic nanoparticles (magnetite) for efficient chronic wounds healing. Composites were obtained directly in the cellulose bacterial culture medium by dispersing various amounts of magnetite nanoparticles during the biosynthesis process. After purification and drying, the membranes were characterized by Raman spectroscopy and X-ray diffraction to reveal the presence of magnetite within the bacterial cellulose matrix. Morphological investigation was employed through SEM and TEM analyses on bionanocomposites. The biocompatibility of these innovative materials was studied in relation to human adipose derived stem cells in terms of cellular morphology, viability, and proliferation as well as scaffolds cytotoxic potential.

Drug absorption and release properties of crosslinked hydrogels based on diepoxy-terminated poly(ethylene glycol)s and aliphatic polyamines--a study on the effect of the gel molecular structure.

Crosslinked hydrogels with well-defined chemical structures and characteristics were prepared through the reaction between diepoxy-terminated poly(ethylene glycol)s of various molecular weights and aliphatic polyamines of different hydrocarbon chain length and functionalities, and the influence of some network parameters (molecular weight between crosslinking points, crosslinking degree, hydrophobic character) upon the absorption and release of drugs of different capacity to interact with the polymer chains was comparatively investigated. Diclofenac sodium (DCFNa) and 5-fluorouracil (5FU) were used as model drugs, based on their dissimilar hydrophobic character and ability of DCFNa to form crown ether-like complexes with PEG chains through the sodium cation. The experiments showed that the most important interactions occurring in these systems were mainly the hydrophobic ones and to a lesser extent the complexation of the Na(+) ion by the PEG chains. Both of them were in favor of DCFNa, resulting in a larger incorporation and a slower release of this one in comparison with 5FU. For both drugs, loading was larger for hydrogels with shorter PEG chains and/or crosslinked with amines with longer hydrocarbon chain or higher functionality. Drug release tests showed a lower rate for stronger drug-network interactions in agreement with the absorption experiments.

Swelling and Diffusion Characteristics of Hydrogels Synthesized from Diepoxy-terminated Poly(ethylene glycol)s and Aliphatic Polyamines

Hydrogels from diepoxy-terminated poly(ethylene glycol)s (PEG) of approximate molecular weights 600, 1,000, 2,000, and 4,000 Da and aliphatic polyamines with different numbers of amine hydrogen atoms (ethylene diamine, diethylenetriamine, triethylenetetramine, tris(2-aminoethyl)amine) in various combinations were synthesized and several means to adjust their water absorption were investigated. It was shown that the equilibrium swelling degree (ESD) can be tuned by varying the cross-linking agent functionality and molecular weight (MW) of the PEG precursor, by either employing single components or mixtures of polyamines or PEG oligomers. The ESD was also influenced by the reaction time and concentration of oligomer in feed. Further investigation of the swelling characteristics and water diffusion in the hydrogels synthesized revealed that the semicrystalline character of the xerogels, influenced mainly by the functionality of the cross-linking agent, PEG molecular weight, and degree of perfection of the network, was the main factor affecting the diffusion coefficient and transport mechanism.

Poly(HydroxyButyrate-co-HydroxyValerate) (PHBHV) Nanocarriers for Silymarin Release as Adjuvant Therapy in Colo-rectal Cancer

The aim of this study was to address one of the major challenges of the actual era of nanomedicine namely, the bioavailability of poorly water soluble drugs such as Silymarin. We developed new, biodegradable, and biocompatible nanosized shuttles for Silymarin targeted delivery in colon-cancer cells. The design of these 100 nm sized carrier nanoparticles was based on natural polymers and their biological properties such as cellular uptake potential, cytotoxicity and 3D penetrability were tested using a colon cancer cell line (HT-29) as the in vitro culture model. Comparative scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements demonstrated that the Silymarin loaded Poly(3-HydroxyButyrate-co-3-HydroxyValerate) (PHBHV) nanocarriers significantly decreased HT-29 cells viability after 6 and 24 h of treatment. Moreover, in vivo-like toxicity studies on multicellular tumor spheroids showed that the Silymarin loaded PHBHV nanocarriers are able to penetrate 3D micro tumors and significantly reduce their size.

Thermosensitive injectable hydrogels from poly(N-isopropylacrylamide)–dextran aqueous solutions: Thermogelation and drug release properties

ABSTRACT Novel injectable thermosensitive hydrogel formulations with improved both water retention (WR) and drug release profile were prepared by adding dextran (DXT) to poly(N-isopropylacrylamide) (PNIPAM) aqueous solutions as a remedy against the demixing/syneresis phenomenon. The addition of the hydrophilic polysaccharide improved the WR of the hydrogel at 37°C from about 12% in the absence of DXT to about 40–55% out of the initial amount introduced, depending on both PNIPAM and DXT concentrations. Also, the 5-fluorouracil release experiments showed an appreciably reduced “burst effect” for the DXT-containing hydrogels. The shape of the release profiles revealed the presence of two stages, differing each other from the point of view of the drug release rate.

Synthesis and Characterization of Composites from Layered Silicates and Homo- and Copolymers of 2-Hydroxyethyl Methacrylate and P-Chloromethyl Styrene Obtained by In Situ Radical (Co)polymerization

The hybrids 2-hydroxyethyl methacrylate – chlorometylstyrene – modified montmorillonite were synthesized by means of “in-situ” radical (co)polymerization. The composites were analysed by thermal analysis (DSC-TGA-MS), Fourier-Transform Infrared Spectroscopy (FT-IR), nuclear magnetic resonance (1H-NMR), X-ray diffraction, and scanning electron microscopy (SEM). The influence of the polymerization conditions and compositions on the thermal stability and morphology of the obtained composites is discussed.