Tissue response to PNIPAM and HPC nanoparticles has been studied by implantation method. The results suggest that both PNIAPM and HPC nanoparticles possess good biocompatibility and they may serve as a good carrier for the applications of controlled delivery. Rheological properties of dispersions of IPN microgels composed of PNIPAM and PAAc have been studied. It is found that the IPN microgel dispersion can undergo a sol-gel transition at temperature above 33°C. In vivo drug release experiments suggest that the gelation procedure creates a diffusion barrier and thus leads to slow release. An emulsion method has been used to grow columnar crystals by mixing PNIPAM microgel dispersions with organic solvents. Effect of both temperature and microgel concentration on formation of columnar crystals has been studied. PNIPAM-co-NMA microgels have been used for the fabrication of crystalline hydrogel films by self-crosslinking microgels. The hydrogel film exhibits an iridescent. The thermally responsive properties and mechanical properties of this film have been studied. Melting temperature (Tm) of colloidal crystals self-assembled with PNIPAM-co-AAc microgels has been investigated as a function of pH, salt concentration and microgel concentration. It is revealed that Tm increases as pH value increases; Tm decreases with increase of salt concentration; Tm increases as microgel concentration increases. Phase behavior of PNIPAM-co-HEAc microgel dispersions has been investigated. It is observed that these microgel dispersions exhibit liquid, crystal, and glass phase. As microgel size increases, crystal phase shifts to low concentration range. As temperature increases, crystal phase shifts to high concentration ranges. These colloidal crystals can be stabilized by NaOH-induced gelation. Effect of NaOH concentration on formation of physical gelation has been investigated.

A liberação controlada de fármacos é um tópico importante para várias iniciativas em nanotecnologia devido ao possível impacto para a sociedade, com a criação de sistemas otimizados que garantam a liberação num sítio específico e a uma taxa controlada. Dentre os vários paradigmas de liberação controlada destaca-se o uso de lipossomos, uma vez que muitos fármacos e drogas podem ser transportados. Este trabalho descreve a fabricação de filmes automontados de lipossomos que incorporam o fármaco ibuprofeno. Os lipossomos foram preparados de dipalmitoil fosfatidil colina (DPPC), dipalmitoil fosfatidil glicerol (DPPG) e palmitoil-oleoil fosfatidil glicerol (POPG), cujas camadas foram alternadas por interações eletrostáticas com camadas do dendrímero PAMAM geração 4. Medidas de espalhamento dinâmico de luz indicaram que a incorporação do ibuprofeno tornou os lipossomos de DPPC e DPPG mais estáveis, com uma diminuição no diâmetro médio de 140 para 74 nm e 132 para 63nm, respectivamente. Ao contrário, os lipossomos de POPG ficaram menos estáveis, com aumento do diâmetro de 110 para 160 nm. A influência na estabilidade foi confirmada em medidas de microscopia de força atômica nos filmes automontados, que mostraram grande tendência à ruptura nos lipossomos de POPG com a incorporação de ibuprofeno. O crescimento dos filmes automontados foi investigado com espectroscopia de fluorescência e uma balança de cristal de quartzo. A intensidade da fluorescência devida ao ibuprofeno aumentou exponencialmente com o número de camadas depositadas, mas não por causa de uma crescente adsorção de ibuprofeno. Ao contrário, a quantidade de material adsorvido nas primeiras camadas aumentou inicialmente, mas depois diminuiu drasticamente após a 6ª. bicamada, e o filme praticamente pára de crescer a partir da 10ª. bicamada. Portanto, a grande fluorescência para filmes espessos deve ser associada a um ambiente favorável, que aumenta a emissão quântica do ibuprofeno. A liberação do ibuprofeno, estudada com medidas de fluorescência, é mais lenta quando incorporado em lipossomos. Em experimentos com uma membrana de diálise, notamos que o tempo de decaimento do ibuprofeno puro é 5,2 h, enquanto este tempo aumentou para 9,2 e 8 h para ibuprofeno encapsulado em lipossomos de DPPG e POPG, respectivamente. O ibuprofeno também foi liberado de filmes automontados contendo lipossomos de DPPG e POPG, o que é promissor para o uso em bandagens (patches). / Controlled drug delivery is a key issue in a number of nanotechnology endeavors owing to the large impact on society that may achieved if improved systems are created which allows for delivery at a specific target and with a controlled rate. Among the various paradigms employed in drug delivery, the use of liposomes is prominent because a variety of drug molecules can be carried. This work describes the fabrication of layer-by-layer (LbL) films made with liposomes incorporating ibuprofen. The liposomes were made with dipalmitoyl phosphatidyl choline (DPPC), dipalmitoyl phosphatidyl glycerol (DPPG) and palmitoyl-oleoyl-phosphatidyl glycerol (POPG), whose layers were alternated with layers of the dendrimer PAMAM generation 4 via electrostatic interactions. According to dynamic light scattering measurements, the incorporation of ibuprofen caused DPPC and DPPG liposomes to become more stable, with a decrease in diameter from 140 to 74 nm and from 132 to 63 nm, respectively. In contrast, liposomes from POPG became less stable, with an increase in size from 110 to 160 nm. These results were confirmed with atomic force microscopy images of LbL films, which showed a large tendency to rupture for POPG liposomes. The film growth was monitored with fluorescence spectroscopy and a quartz crystal microbalance (QCM). The fluorescence intensity arising from ibuprofen increased exponentially with the number of layers, but this was not caused by an increased adsorption of ibuprofen. Instead, the QCM measurements showed that the amount of material adsorbed increases initially with the number of PAMAM/liposome(ibuprofen) layers, but after the 6th bilayer it decreases sharply and film growth practically stops after the 10th layer. Therefore, the inevitable conclusion is that the increased fluorescence is due to a favorable environment for the ibuprofen, whose quantum emission efficiency increases with the number of layers deposited. Also using fluorescence measurements, we noted that release of ibuprofen was delayed when incorporated in liposomes. For instance, in a membrane dialysis experiment, the characteristic decay time was 3.5 h for ibuprofen in solution, whereas this time increased to 9.2 and 8 h for ibuprofen encapsulated into DPPG and POPG liposomes, respectively. Ibuprofen could also be released from the LbL films made with DPPG and POPG liposomes, which is promising for further use in patches.

<p>As amorphous solid dispersions (ASDs) are more widely employed as a formulation strategy for poorly water-soluble drugs, there is a pressing need to increase the drug loading in these formulations. The drug loading is typically kept low to obtain the desired drug release rate, but often results in large or even multiple dosage units, which is undesirable from a patient compliance perspective. We have identified the cause of this conundrum to be the drug loading dependent dissolution mechanism of ASDs. At low drug loadings, the dissolution rate of ASDs is polymer-controlled, while at high drug loadings, the dissolution rate is drug-controlled and considerably slower. This phenomenon is most pronounced for ASDs with hydrophilic polymers, such as poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA) and the change in dissolution mechanism from being polymer-controlled to drug-controlled has been attributed to water-induced amorphous-amorphous phase separation (AAPS) in higher drug loading ASD matrices of hydrophilic polymers. The drug loading limit for this switch has been found to be dependent on drug properties as well as drug-polymer interactions. Interestingly, drug-polymer hydrogen bonding interaction has been found to be detrimental and decrease the drug loading limit for polymer-controlled release while drug log P did not have any impact on this limit. Variable dissolution temperature studies indicated a detrimental impact on the polymer-controlled drug loading limit when the drug-rich phase (of phase separated ASD matrix) exists in a glassy state. ASDs with relatively hydrophobic polymers, such as hypromellose acetate succinate (HPMCAS), have been found to be polymer-controlled up to higher drug loadings. The mechanistic understanding obtained in this body of work can thus be adopted to develop strategies enabling ASD formulations with optimized performance and improved drug loading.</p>

Despite of all the research going on for the treatment of ocular diseases, age-related macular degeneration (AMD) remains one of the serious vision threatening disease worldwide. Choroidal neovascularization, a pathophysiological characteristic of wet AMD, is the growth of anomalous blood vessels in the eye choroidal layer. Neovascularization is a key factor in AMD and thus anti-angiogenic therapy is beneficial in reducing the development of new abnormal blood vessels to prevent progression of AMD. Axitinib, multi-receptor tyrosine kinase inhibitor, is a small molecule that works by blocking vascular endothelial growth factor receptors (VEGFR) and platelet derived growth factor receptors (PDGFR) responsible for developing neovascularization. Thus, goal of this study was to develop and characterise a sustained release formulation of Axitinib loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles. The nanoparticles were characterized for particle size and zeta potential as well as using DSC, TEM and in vitro drug release profile. The cytotoxicity of the formulation was evaluated on human retinal pigmented epithelium ARPE19 cells by MTT assay. The cellular uptake, anti-migration assay, and VEGF expression levels were found out in vitro using cells. The optimized formulation was 131.33 ± 31.20 nm in size with -4.63± 0.76 mV zeta potential. Entrapment efficiency was found to be 87.9 ± 2.7%. The cytotoxicity of ARPE19 cells was less than 12% for nanoparticles suggesting the in vitro compatibility at 10 µM concentration of drug. Cellular uptake, anti-migration assay and VEGF expression levels for the nanoparticles had greater uptake, had significant anti-angiogenic potential and exhibited inhibition of VEGF activity. The results showed successful development of axitinib loaded PLGA nanoparticles as an alternative potential treatment option for AMD.

Indiana University-Purdue University Indianapolis (IUPUI) / The biodegradation of the hybrid layer of dental restorations is due in part to the degradation of the demineralized collagen by matrix metalloproteinases (MMPs). During the bonding procedure, phosphoric acid/acidic primers activate MMPs that degrade denuded type I collagen. As a result, the hybrid layer loses its integrity overtime, leading to the failure of the resin composite restoration. This study aimed to evaluate doxycycline (DOX) for its effects on preventing the degradation of the hybrid layer through the modification of the dental adhesive with aluminosilicate clay nanotubes (HNT) loaded with doxycycline. Doxycycline was encapsulated into HNT at three distinct concentrations (10%, 20% and 30% DOX, w/v). The increases in the concentration of doxycycline significantly increased the amount of doxycycline that was encapsulated into HNT and the drug loading into the HNT. Conversely, the encapsulation efficiency was significantly decreased with the increases in concentration of doxycycline. The modified adhesives were fabricated by incorporation of DOX-encapsulated HNT into a commercially available dental adhesive (Adper Scotchbond Multi-Purpose, SBMP). The degree of conversion (DC), Knoop microhardness, doxycycline release profiles, the biological activity (antibacterial and anti-MMP activity), and cytocompatibility of the modified adhesives were investigated. There were no statistically significant differences (p &gt; 0.05) in DC and Knoop microhardness compared to the control (SBMP). None of the adhesive eluates was cytotoxic to the human dental pulp stem cells. Although higher concentrations of doxycycline led to a higher release of doxycycline from the modified adhesives, the differences were not significant (p = 0.259) among the groups (10%, 20% and 30% DOX). A significant growth inhibition of S. mutans and L. casei by direct contact illustrated successful encapsulation of doxycycline into the modified adhesives. Doxycycline released from the modified adhesives did not inhibit the growth of both cariogenic bacteria but inhibited MMP-1 activity. The results suggested that subantimicrobial levels of doxycycline were gradually released. The immediate microtensile bond strengths were not significantly different from those of the control (SBMP), suggesting no negative effect of doxycycline on dentin bonding (only 10% DOX were investigated). The long-term resin-dentin bond durability should be evaluated.

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