An augmented delivery of the anticancer agent, curcumin, to the colon

This work describes the formulation aspects of an orally viable curcumin-containing mucoadhesive nanoparticulate system for management of colon cancer. Curcumin is documented to possess anticancer properties whilst modified citrus pectin yields a galactose functionality capable of inhibiting the growth and proliferation of colon cancer cells due to antagonism to galectin-3 (Gal-3). A successfully formulated curcumin containing chitosan-modified citrus pectinate nanoparticles (MCPCNPs) registered a z-average of 178 nm (± 0.896) and a positive surface charge of + 35.7 mV (± 1.41). The MCPCNPs presented high mucoadhesion propensity in the colonic region/ media and minimal at pH 1.2 (stomach). There was approximately 18 % curcumin release at pH 1.2 over 2 h and up to 68% release in the 33% (w/v) caecal medium over 24 h. The data obtained strongly suggests that the formulated MCPCNPs have the potential to be applied as an orally deliverable colon cancer formulation alternative in the treatment of colon cancer

Multiboronic acid-conjugated chitosan scaffolds with glucose selectivity to insulin release

The principal challenge for the use of boronic acids (BA) as glucose sensors is their lack of specificity for glucose. We examined the selectivity of and insulin release from two boronic acids- (2-formyl-3-thienylboronic acid (FTBA) and 4-formylphenylboronic acid (FPBA)) conjugated chitosan scaffolds to glucose and fructose. Adsorption of glucose to BA: chitosan conjugates was dose-dependent up to 1:1 at 35 and 42% for FPBA and FTBA respectively but the FTBA conjugates adsorbed more glucose and fructose at respective FPBA ratios. The affinity of both BA conjugates to glucose decreased with increase in BA ratio. On the other hand, the affinity of both BA conjugates for fructose decreased from ratio 1:1 to 2:1 then rose again at 3:1. Insulin release from FPBA nanoparticles (FPBAINP) and FTBA nanoparticles (FTBAINP) were both concentration-dependent within glyceamically relevant values (1–3 mg/ml glucose and 0.002 mg/ml fructose). Furthermore, the total amounts of insulin released from FPBAINP in both the media were higher than from FTBAINP. Both FPBAINP and FTBAINP have the potential for development as a glucose-selective insulin delivery system in physiological settings

A dual-application poly (DL-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (DL-lactic-co-glycolic acid), (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37°C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37°C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37°C in situ

Multiboronic acid-conjugated chitosan scaffolds with glucose selectivity to insulin release

The principal challenge for the use of boronic acids (BA) as glucose sensors is their lack of specificity for glucose. We examined the selectivity of and insulin release from two boronic acids- (2-formyl-3-thienylboronic acid (FTBA) and 4-formylphenylboronic acid (FPBA)) conjugated chitosan scaffolds to glucose and fructose. Adsorption of glucose to BA: chitosan conjugates was dose-dependent up to 1:1 at 35 and 42% for FPBA and FTBA respectively but the FTBA conjugates adsorbed more glucose and fructose at respective FPBA ratios. The affinity of both BA conjugates to glucose decreased with increase in BA ratio. On the other hand, the affinity of both BA conjugates for fructose decreased from ratio 1:1 to 2:1 then rose again at 3:1. Insulin release from FPBA nanoparticles (FPBAINP) and FTBA nanoparticles (FTBAINP) were both concentration-dependent within glyceamically relevant values (1–3 mg/ml glucose and 0.002 mg/ml fructose). Furthermore, the total amounts of insulin released from FPBAINP in both the media were higher than from FTBAINP. Both FPBAINP and FTBAINP have the potential for development as a glucose-selective insulin delivery system in physiological settings

Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles

Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer

PLGA-Gold Nanocomposite: Preparation and Biomedical Applications

A composite system consisting of both organic and inorganic nanoparticles is an approach to prepare a new material exhibiting “the best of both worlds”. In this review, we highlight the recent advances in the preparation and applications of poly(lactic-co-glycolic acid)-gold nanoparticles (PLGA-GNP). With its current clinically use, PLGA-based nanocarriers have promising pharmaceutical applications and can “extract and utilize” the fascinating optical and photothermal properties of encapsulated GNP. The resulting “golden polymeric nanocarrier” can be tracked, analyzed, and visualized using the encapsulated gold nanoprobes which facilitate a better understanding of the hosting nanocarrier’s pharmacokinetics and biological fate. In addition, the “golden polymeric nanocarrier” can reveal superior nanotherapeutics that combine both the photothermal effect of the encapsulated gold nanoparticles and co-loaded chemotherapeutics. To help stimulate more research on the development of nanomaterials with hybrid and exceptional properties, functionalities, and applications, this review provides recent examples with a focus on the available chemistries and the rationale behind encapsulating GNP into PLGA nanocarriers that has the potential to be translated into innovative, clinically applicable nanomedicine.A.M.A. acknowledge funding support from the University of Jordan. The APC was funded by the University of Illinois at Urbana-Champaign

Calculation of αˉQ.E.D.\bar{\alpha}_{\rm Q.E.D.} on the Z

We perform a new, detailed calculation of the hadronic contributions to the running electromagnetic coupling, $\bar{\alpha}$, defined on the Z particle (91 GeV). We find for the hadronic contribution, including radiative corrections, 10^5\times \deltav_{\rm had.}\alpha(M_Z^2)= 2740\pm12, or, excluding the top quark contribution, 10^5\times \deltav_{\rm had.}\alpha^{(5)}(M_Z^2)= 2747\pm12. Adding the pure QED corrections we get a value for the running electromagnetic coupling of $$\bar{\alpha}_{\rm Q.E.D.}(M_Z^2)= {{1}\over{128.965\pm0.017}}.$$Comment: Version to appear in Phys. Rev. D. Plain TeX fil

Challenges and considerations of applying nature-based solutions in low- and middle-income countries in Southeast and East Asia

Low- and middle-income countries in Southeast and East Asia face a range of challenges related to the rapid pace of urbanisation in the region, the scale of pollution, climate change, loss of ecosystem services and associated difficulties for ecological restoration. Possible pathways towards a more sustainable future lie in the applications of nature-based solutions (NBS). However, there is relatively little literature on the application of NBS in the region, particularly Southeast Asia. In this paper we address this gap by assessing the socio-ecological challenges to the application of NBS in the region – one of the most globally biodiverse. We first provide an overview and background on NBS and its underpinnings in biodiversity and ecosystem services. We then present a typology describing five unique challenges for the application of NBS in the region: (1) Characteristics of urbanisation; (2) Biophysical environmental and climatic context; (3) Environmental risks and challenges for restoration; (4) Human nature relationships and conflicts; and (5) Policy and governance context. Exploiting the opportunities through South-South and North-South collaboration to address the challenges of NBS in Southeast and East Asia needs to be a priority for government, planners and academics.Peer reviewe

Modelling urban growth evolution and land-use changes using GIS based cellular automata and SLEUTH models: the case of Sana'a metropolitan city, Yemen.

An effective and efficient planning of an urban growth and land use changes and its impact on the environment requires information about growth trends and patterns amongst other important information. Over the years, many urban growth models have been developed and used in the developed countries for forecasting growth patterns. In the developing countries however, there exist a very few studies showing the application of these models and their performances. In this study two models such as cellular automata (CA) and the SLEUTH models are applied in a geographical information system (GIS) to simulate and predict the urban growth and land use change for the City of Sana’a (Yemen) for the period 2004–2020. GIS based maps were generated for the urban growth pattern of the city which was further analyzed using geo-statistical techniques. During the models calibration process, a total of 35 years of time series dataset such as historical topographical maps, aerial photographs and satellite imageries was used to identify the parameters that influenced the urban growth. The validation result showed an overall accuracy of 99.6 %; with the producer’s accuracy of 83.3 % and the user’s accuracy 83.6 %. The SLEUTH model used the best fit growth rule parameters during the calibration to forecasting future urban growth pattern and generated various probability maps in which the individual grid cells are urbanized assuming unique “urban growth signatures”. The models generated future urban growth pattern and land use changes from the period 2004–2020. Both models proved effective in forecasting growth pattern that will be useful in planning and decision making. In comparison, the CA model growth pattern showed high density development, in which growth edges were filled and clusters were merged together to form a compact built-up area wherein less agricultural lands were included. On the contrary, the SLEUTH model growth pattern showed more urban sprawl and low-density development that included substantial areas of agricultural lands

Formation of a morphine-conditioned place preference does not change the size of evoked potentials in the ventral hippocampus–nucleus accumbens projection

Abstract In opioid addiction, cues and contexts associated with drug reward can be powerful triggers for drug craving and relapse. The synapses linking ventral hippocampal outputs to medium spiny neurons of the accumbens may be key sites for the formation and storage of associations between place or context and reward, both drug-related and natural. To assess this, we implanted rats with electrodes in the accumbens shell to record synaptic potentials evoked by electrical stimulation of the ventral hippocampus, as well as continuous local-field-potential activity. Rats then underwent morphine-induced (10 mg/kg) conditioned-place-preference training, followed by extinction. Morphine caused an acute increase in the slope and amplitude of accumbens evoked responses, but no long-term changes were evident after conditioning or extinction of the place preference, suggesting that the formation of this type of memory does not lead to a net change in synaptic strength in the ventral hippocampal output to the accumbens. However, analysis of the local field potential revealed a marked sensitization of theta- and high-gamma-frequency activity with repeated morphine administration. This phenomenon may be linked to the behavioral changes—such as psychomotor sensitization and the development of drug craving—that are associated with chronic use of addictive drugs