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P-glycoprotein (P-gP) efflux-mediated multidrug resistance is a fundamental aspect of chemotherapeutic failure in oncology. The current study aims to deliver paclitaxel (PTX) specifically at the target site with improved in vivo efficacy of poorly permeable PTX against solid tumors. Multifunctional polymeric micelles as targeted delivery have been devised for loading and release of PTX. Mucoadhesion, permeation enhancement, oral pharmacokinetics, biodistribution, and toxicological studies were carried out to fully elucidate the therapeutic outcomes of the polymeric micelles. Ex vivo permeation studies indicated a 7.89-fold enhancement in the permeation of PTX with mucopermeating papain functionalized thiolated redox micelles (PT-R-Ms) compared to the pure PTX. Moreover, PT-R-Ms exhibited a higher percentage of apoptotic cells (42.9 ± 0.07%) compared to pure PTX. Biodistribution studies revealed that fluorotagged PT-RMs accumulated in excised tumors and organs. The higher fluorescence intensity indicated the mucopermeation of micelles across the intestine. The orally administered PT-R-Ms efficiently overcome intestinal barriers and inhibit the P-gP efflux pump, resulting in increased bioavailability of PTX (up to 8-fold) in comparison to pure PTX. The enhanced anti-tumor efficacy and reduced toxic effects are key aspects of efficient cancer therapy. This study demonstrates that the use of mucopermeating PT-R-Ms is an encouraging approach to overwhelm the permeation barrier in cancer treatment.

<p>To condense saving-investment gap, transformation of technology, creation of employment opportunities and more importantly, increasing economic development of host countries, Foreign Direct Investment (FDI) is proven to be a significant source of investment predominantly for developing countries. Numerous standing studies have scrutinized the economic impact of terrorism and political stability by referring to decrease in FDI. This study empirically enlightens the determinants of FDI for Pakistan over the period 1970 to 2013, by using annual secondary time series data. Adopting the optimistic approach, in this study, variables in the combination of terrorism, political stability, trade openness and GDP have been analyzed applying Ordinary Least Square (OLS) method. As expected, the projected results confirm that GDP, trade openness and political stability have positive and significant impact whilst terrorism has negative influence on FDI inflows in Pakistan. Because of the political stability along with stable GDP growth rate, inverse impact of terrorism has been found statistically insignificant.</p>

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