Rodrigo L. Oréfice

Formation of ion pairing as an alternative to improve encapsulation and stability and to reduce skin irritation of retinoic acid loaded in solid lipid nanoparticles.

This work aims to investigate the influence of the formation of ion pairing between all-trans retinoic acid (RA) and a lipophilic amine (stearylamine; STE) on the drug encapsulation efficiency (EE) and stability of solid lipid nanoparticles (SLNs). The SLNs were characterized for EE and size. The EE and particle size were significantly improved and reduced, respectively, when the surfactant or co-surfactant concentration increased. However, while the formulation without STE allowed only 13% of RA encapsulation, the EE for RA-STE-loaded SLNs was 94%. The stability studies showed a significant decrease in EE for the SLNs without STE, while, for SLNs loaded with RA and STE, the EE remained constant after 360 days. The interactions among ion pairing components and the lipid matrix were investigated through small-angle X-ray scattering (SAXS). The SAXS analysis revealed the presence of RA in the crystalline form in SLNs without ion pairing, while crystalline RA was not observed in SLNs loaded with RA/amine. Skin irritation studies showed that the SLNs loaded with the ion pairing were significantly less irritating when compared to the marketed RA-cream. This novel SLN formulation represents a promising alternative for topical treatment of acne with RA.

Synthesis and characterization of biodegradable polyurethane films based on HDI with hydrolyzable crosslinked bonds and a homogeneous structure for biomedical applications.

Synthetic biodegradable polymers are considered strategic in the biomaterials field and are used in various applications. Among the polymers used as biomaterials, polyurethanes (PUs) feature prominently due to their versatility and the ability to obtain products with a wide range of physical and mechanical properties. In this work, new biodegradable polyurethane films were developed based on hexamethylene diisocyanate (HDI) and glycerol as the hard segment (HS), and poly(caprolactone) triol (PCL triol) and low-molecular-weight poly(ethylene glycol) PEG as the soft segment (SS) without the use of a catalyst. The films obtained were characterized by structural, mechanical and biological testing. A highly connected network with a homogeneous PU structure was obtained due to crosslinked bonds. The films showed amorphous structures, high water uptake, hydrogel behavior, and susceptibility to hydrolytic degradation. Mechanical tests indicated that the films reached a high deformation at break of up to 425.4%, an elastic modulus of 1.6 MPa and a tensile strength of 3.6 MPa. The materials presented a moderate toxic effect on MTT assay and can be considered potential materials for biomedical applications.

Aplicações farmacêuticas de polímeros

Polymers are very versatile for a series of applications including pharmaceutical applications. Natural polymers, modified natural polymers and synthetic polymers are employed as excipients in the manufacture of cosmetics and systems for conventional and modified delivery of drugs. More recently, polymers have been developed to be able to modulate and deliver drugs to target places. Biodegradable polymers, bioadhesives, biomimetic materials and responsive hydrogels have been included in pharmaceutical formulations. The advances in the concept of new drug delivery systems will only be possible with the development of polymers specifically designed for the pharmaceutical field. Therefore, this manuscript intends to review and report information regarding the use of polymers in pharmaceutical applications that can be useful in designing new systems with improved performance.

Sol-Gel Transition and Structural Evolution on Multicomponent Gels Derived from the Alumina-Silica System

The capacity of the sol-gel process of producing highly pure, homogeneous alumina-silica based materials had been demonstrated in the last few years. However, a full understanding on the mechanisms associated to sol formation and sol to gel transition has not yet been achieved and is required for the development of a new generation of nano-structurally tailored materials that will significantly enhance the technological importance of the sol-gel process. In this work, tetraethyl orthosilicate (TEOS) and aluminum isopropoxide were used to prepare materials within the entire silica-alumina system. Process parameters, such as gelation time, were correlated to variables of the initial stage of the process, such as pH, temperature of hydrolysis and water/alkoxide ratio. The obtained gels were dried at 105°C and subsequently heat treated at 500 and 1100°C for 3 hours. X-ray diffraction and infrared spectroscopy were used to characterize the materials and phase transformations. Structural information obtained from phase characterization and phase transformations was correlated to the effects of the process variables on sol formation and gelation, providing insights related to the mechanisms involved. The influence of temperature of aluminum isopropoxide hydrolysis on peptization and gelation of the mixtures was noted. The different behavior of mixtures hydrolyzed at low and high temperatures was suggested to be caused by different mechanisms of surface charge formation on the structurally different aluminum hydroxides. Monophasic and diphasic mullite xerogels were produced by changing temperature of aluminum isopropoxide hydrolysis, and led to formation of mullite and Al−Si spinel phases respectively, when treated at 1100°C.

Sol-gel silica based networks with controlled chemical properties

Abstract In this work, different chemical functionalities, both organic and inorganic, were inserted in a silica glass based sol–gel derived network to create specific chemical activities. Modified silica glass networks were prepared by reacting alkoxysilanes with different chemical functionalities, such as tetraethoxysilane (TEOS), aminopropyl triethoxysilane (APS) and mercaptopropyl triethoxysilane (MPTS), among others. The obtained gels were evaluated by using infrared spectroscopy, mercury picnometry and electron microscopy. The chemical activity of the created multifunctional surfaces was evaluated by the ability of the incorporated proteins to remain adsorbed onto the different gels. Porcine insulin (PI) and bovine serum albumin (BSA) were impregnated into modified networks and desorption of those proteins was monitored. Results showed that gels with multifunctionalities regularly dispersed can be successfully produced by optimizing some of the processing parameters of the gels, such as pH and concentration of reactants. Results also revealed that the type and concentration of chemical functionalities within the gels regulate the ability of incorporated proteins to remain adsorbed on them, suggesting that chemically patterned surfaces and interfaces can be prepared which regulate protein–substrate interactions.

Novel multicomponent silicate–poly(vinyl alcohol) hybrids with controlled reactivity

Abstract By a combination of inorganic and organic species at a molecular level, a new series of biomaterials having optimal controllable properties can be fabricated. The goal of this work is to determine how the reactivity of the composites (inorganic–organic hybrids) can be controlled by altering the nanostructure of the materials. Hybrids were synthesized by reacting poly(vinyl alcohol) (PVA) in acidic solution with either tetraethoxy silane (TEOS) or tetramethoxy silane (TMOS). The inorganic phase was also modified by incorporating calcium and phosphate compounds. The properties of the hybrids were determined by swelling experiments, infrared spectroscopy, and scanning electron microscopy/microprobe analysis. Transparent PVA–silicate hybrid free-standing films, having a range of compositions within the system, were produced by allowing the rate of hydrolysis of the alkoxide to be compatible with the kinetics of the dissolution processes of both the polymer and calcium-phosphate compounds. Results obtained from swelling experiments and infrared spectroscopy showed that the crosslink density can be increased when hybrids are prepared with larger concentrations of the inorganic component. Moreover, hybrids prepared at temperatures as high as 60°C have, among other properties, greater crosslink densities and inorganic phases with larger amounts of S–O–Si bridging bonds. Swelling experiments also showed that the obtained hybrids varied in their reactivities ranging from fast dissolution to hydrogel properties. We also demonstrate that the degree of reactivity can be controlled by manipulating structural factors of the hybrids such as the crosslink density, proportion of the phases and composition of the inorganic phase, among others.

In situ evaluation of the polymerization kinetics and corresponding evolution of the mechanical properties of dental composites

Polymer composites have been used in dental applications for more than 25 years. Although their properties and behavior have been systematically improved, they still are not able to produce dental restorations chemically, dimensionally and mechanically stable for long periods of time. Low degrees of monomer conversion and poor processing control are some of the main features responsible for the materials instability. In this work, the monomer conversion of dental composites during visible light irradiation was in situ monitored by infrared spectroscopy. The relationship between degree of conversion and mechanical properties was obtained by evaluating the microhardness of composites with different degrees of conversion. The relationship obtained was then used to identify the evolution of the mechanical properties during photopolymerization.

FTIR and UV‒vis study of chemically engineered biomaterial surfaces for protein immobilization

The biomaterials research field has broadened in the last 3 decades, including replacement of diseased or damaged parts, assist in healing, correct and improve functional abnormality, drug delivery systems, immunological kits and biosensors. Proteins play crucial role in almost every biological system. They are involved in enzymatic catalysis, transport and storage, coordinated motion, mechanical support, immune protection, control of growth and cell differentiation among many others. The immobilization of proteins onto surface functionalized substrates has been one of the most promising areas in bioengineering field. It is important to note that the term immobilization can refer either to a temporary or to a permanent localization of the biomolecule on or within a support. Proteins have very particular chain configurations and conformations that promote high levels of specificity during chemical interactions. In the present work, we aimed to study the phenomenon of protein immobilization onto biomaterial with chemically engineered surface. We have tailored the surface of the porous gels of SiO2 with 5 different silane surface modifying agents: tetraethoxysilane (TEOS), 3‒mercaptopropyltrimethoxysilane (MPTMS) and 3‒aminopropyltriethoxysilane (APTES), 3‒glycidoxypropyltrimethoxysilane (GPTMS) and 3‒isocyanatopropyltriethoxysilane (ICPES). Fourier Transform Infrared Spectroscopy (FTIR) was used to characterize the presence of all specific chemical groups in the materials. The surface functionalized gels were then immersed in porcine insulin (PI) solutions for protein immobilization. The incorporation of protein within the gels was also monitored by FTIR spectroscopy. The kinetics of protein adsorption and desorption from the gel matrix in vitro tests were monitored by UV‒visible spectroscopy. We could not observe any evidence of denaturation of insulin after its desorption from gel matrices using UV‒visible spectroscopy technique. In vivo tests with adult male rats were used to verify the immobilized insulin bioactivity after implantation of different biomaterial with functionalized surfaces. Plasma glucose levels were obtained by using the Glucose GOD‒ANA Colorimetric Assay. All surface modified materials have presented acute hypoglycemic peak response associated with the insulin bioactivity.

Development of a new solid lipid nanoparticle formulation containing retinoic acid for topical treatment of acne

The development of solid lipid nanoparticles (SLN) containing all-trans retinoic acid (RA) is an interesting approach to topical treatment of acne. SLN has potential for controlled release and follicular penetration, which can reduce adverse effects in comparison with conventional formulations. However, the encapsulation efficiency (EE) of RA in SLN is usually low, unless a high surfactant/lipid ratio is used. The aim of this work was to develop SLN with high EE using a low surfactant/lipid ratio. Different formulations of RA-loaded SLN were prepared using glyceryl behenate as lipid matrix. The particle size, EE, zeta potential and differential scanning calorimetry (DSC) were investigated. High EE in SLN was obtained with addition of amines. These results indicate that the utilization of amines is an interesting approach to improve the EE of RA in SLN using a low surfactant/lipid ratio.

Photopolymerizable and injectable polyurethanes for biomedical applications: synthesis and biocompatibility.

Two types of photopolymerizable and injectable polyurethane acrylates (PUAs), based on poly(propylene glycol) or poly(caprolactone diol) and hydroxyethyl methacrylate, were synthesized and characterized in order to obtain information regarding their use as an injectable material for biomedical applications. Structural characteristics of the biomaterials, including the degree of phase separation, were evaluated by Fourier transform infrared spectroscopy. The viscosities of the obtained biomaterials make them suitable for injection, molding and photopolymerization using visible light, as demonstrated by the injection test. The cured polymers had mechanical properties comparable to those of certain soft tissues, such as skin. An in vitro cell-polyurethane cytotoxicity study was carried out with mesenchymal stem cells from rat tibias and femurs. The proliferation/viability of the cells in the presence of the synthesized material was assessed by the MTT assay, collagen synthesis analysis and the expression of alkaline phosphatase. The results that were obtained through the in vitro tests indicated that PUAs are cytocompatible. The in vivo experiments were correlated with the in vitro tests and showed low levels of toxicity for the obtained biomaterials. Histology cross-sections showed that the biomaterials induced no significant inflammatory reaction. Our study demonstrates the potential for using synthesized photocurable polyurethanes in biomedical applications. Furthermore, the obtained injectable polymer systems employ minimally invasive procedures and can be molded in situ before photopolymerization with visible light.