Mucoadhesive nanostructured systems comprising poloxamer 407 and Carbopol 974P
have already demonstrated good mucoadhesion, as well as improved mechanical and rheological properties. Curcumin ...displays excellent biological activity, mainly in oral squamous cancer; however, its physicochemical characteristics hinder its application. Therefore, the aim of this study was to develop nanostructured formulations containing curcumin for oral cancer therapy. The photophysical interactions between curcumin and the formulations were elucidated by incorporation kinetics and location studies. They revealed that the drug was quickly incorporated and located in the hydrophobic portion of nanometer-sized polymeric micelles. Moreover, the systems displayed plastic behavior with rheopexy characteristics at 37 °C, viscoelastic properties and a gelation temperature of 36 °C, which ensures increased retention after application in the oral cavity. The mucoadhesion results confirmed the previous findings with the nanostructured systems showing a residence time of 20 min in porcine oral mucosa under flow system conditions. Curcumin was released after 8 h and could permeate through the porcine oral mucosa. Cytotoxicity testing revealed that the formulations were selective to cancer cells over healthy cells. Therefore, these systems could improve the physicochemical characteristics of curcumin by providing improved release and permeation, while selectivity targeting cancer cells.
Current oral squamous cell carcinoma chemotherapies demonstrate off-target toxicity, which could be reduced by local delivery. Curcumin acts via many cellular targets to give anti-cancer properties; ...however the bioavailability is hindered by its physicochemical characteristics. The incorporation of curcumin into emulgel systems could be a promising approach for its solubilization and delivery. The aim of this work was to develop emulgel systems containing curcumin for the treatment of oral cancer. The emulgels containing curcumin were prepared with poloxamer 407, acrylic acid derivatives, oil phase (sesame oil or isopropyl myristate). The more stable system was evaluated for mechanical and rheological properties, as well as, the in vitro drug release profile, permeation and cytotoxic potential to oral mucosa models. The flow-throw system evidenced that the formulations could keep 5 min over porcine oral mucosa. Emulgel showed pseudoplastic behavior and a gelation temperature of 33 °C, which ensure their higher consistency. In addition, 70% of the incorporated curcumin was released within 24 h in an in vitro drug release study and could permeate porcine oral mucosa. Monolayers cultures and tissue-engineered models showed the selectivity of the drug and systems for tumor cells. The physicochemical properties, subsequent release and permeation of curcumin to selectivity kill cancer cells could be improved by the incorporation into emulgel systems.
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The aim of the project was to test the hypothesis that substrate stiffness will affect MSC proliferation and differentiation. In order to achieve this two systems were developed; a natural fibrin ...substrate, whereby altering the concentration of fibrinogen changes the stiffness of the resultant gel and an artificial PDMS substrate where the stiffness is controlled by altering the degree of crosslinking. To determine the effect of various fibrin matrices, providing more physiological growth conditions, on the MSC phenotype; cells were cultured on the gels and then analysed or re-plated onto TCP before analysis. It was found that cells, that had an initial 7-day culture period on the fibrin, proliferated. and maintained their osteogenic differential potential better when compared to cells pre-cultured on TCP. Similarly, a concentration relationship between colony number and fibrin concentration was seen with a decrease in colony number as the fibrin number increased suggesting that' progenitor cell numbers are better maintained on low-stiffness gels. Furthermore, direct culture on the gels demonstrated a stiffness related increase in colony number. PDMS is easily produced with a large range of mechanical properties. Uncoated PDMS does not support MSC attachment and growth in vitro and therefore an acrylic acid coating was applied. Although XPS analysis was unable to establish that a complete coating was deposited on all of the substrates, once coated the PDMS supported MSC attachment and growth. CFU-f efficiency was not directly altered by the mechanical properties of the underlying substrate, however, the differentiation of the cells showed a trend; with an increase in osteoblastic differentiation as the stiffness increased. This trend was also seen under high-density culture conditions with no correlation to the rate of proliferation. Although the exact mechanism is unknown the data presented here supports the concept that substrate signals influence MSC growth and differentiation.
The aim of the project was to test the hypothesis that substrate stiffness will affect MSC proliferation and differentiation. In order to achieve this two systems were developed; a natural fibrin ...substrate, whereby altering the concentration of fibrinogen changes the stiffness of the resultant gel and an artificial PDMS substrate where the stiffness is controlled by altering the degree of crosslinking. To determine the effect of various fibrin matrices, providing more physiological growth conditions, on the MSC phenotype; cells were cultured on the gels and then analysed or re-plated onto TCP before analysis. It was found that cells, that had an initial 7-day culture period on the fibrin, proliferated. and maintained their osteogenic differential potential better when compared to cells pre-cultured on TCP. Similarly, a concentration relationship between colony number and fibrin concentration was seen with a decrease in colony number as the fibrin number increased suggesting that' progenitor cell numbers are better maintained on low-stiffness gels. Furthermore, direct culture on the gels demonstrated a stiffness related increase in colony number. PDMS is easily produced with a large range of mechanical properties. Uncoated PDMS does not support MSC attachment and growth in vitro and therefore an acrylic acid coating was applied. Although XPS analysis was unable to establish that a complete coating was deposited on all of the substrates, once coated the PDMS supported MSC attachment and growth. CFU-f efficiency was not directly altered by the mechanical properties of the underlying substrate, however, the differentiation of the cells showed a trend; with an increase in osteoblastic differentiation as the stiffness increased. This trend was also seen under high-density culture conditions with no correlation to the rate of proliferation. Although the exact mechanism is unknown the data presented here supports the concept that substrate signals influence MSC growth and differentiation.
Solid tumours display varied oxygen levels and this characteristic can be exploited to develop new diagnostic tools to determine and exploit these variations. Oxygen is an efficient quencher of ...emission of many phosphorescent compounds, thus oxygen concentration could in many cases be derived directly from relative emission intensity and lifetime. In this study, we extend our previous work on phosphorescent, low molecular weight platinum(II) complex as an oxygen sensing probe to study the variation in oxygen concentration in a viable multicellular 3D human tumour model. The data shows one of the first examples of non-invasive, real-time oxygen mapping across a melanoma tumour spheroid using one-photon phosphorescence lifetime imaging microscopy (PLIM) and a small molecule oxygen sensitive probe. These measurements were quantitative and enabled real time oxygen mapping with high spatial resolution. This combination presents as a valuable tool for optical detection of both physiological and pathological oxygen levels in a live tissue mass and we suggest has the potential for broader clinical application.
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