The Making of Benazir Income Support Program

The Benazir Income Support Program (BISP), introduced in 2008-09, is a unique cash support scheme for economically stressed families. Its uniqueness arises from several facets. The cash transfers are provided only to women aged over 18 years and have been ever married. It is unconditional and aimed at supplementing income as opposed to alleviating poverty. It was politically neutral, given that the facility to identify potential beneficiaries was extended to all parliamentarians, irrespective of party affiliation. A set of filters, applied electronically, ensured objectivity in beneficiary selection. Disbursement mechanism was automated to ensure minimal leakage. This paper outlines the process of the preparatory work that went into designing BISP – the conceptual debates, the beneficiary identification and disbursement procedures, etc. – involving a combination of high quality research with political decision making. It also addresses the debates surrounding BISP, cites independent empirical studies that show that the parliamentarian-based beneficiary selection mechanism was efficient and equitable and did indeed cover the deserving, and also responds to the variety of criticisms. ______

Synthesis and Characterization of Drug Loaded Biodegradable Nanoparticles for Enhanced Bio-Distribution

Glioblastoma multiform (GBM) and Non-small cell lung cancer (NSCLC) are most invasive and uniformly fatal type of brain and lung cancer respectively, with median survival of less than 20 months after diagnosis even with the most aggressive treatment that includes surgery, radiation, and systemic chemotherapy. Currently many chemotherapeutic anticancer drugs are being used in clinical trials which inhibit tumor growth by inhibiting certain pathways inside cancer cells. Luteolin and Ellipticine are plant derived compounds of potent antitumor activity, class of topoisomerase II inhibitor which intercalates with DNA and makes DNA adduct and kill cancer cells. Another class of drugs is polo-like kinase (PLK) inhibitors; among those BI-2536 is highly potent anticancer PLK inhibitor with IC50 of less than 0.9 nM is recently abandoned from phase II trials due to adverse neutropenic effects via systemic delivery. Major limitation of GBM chemotherapy is highly selective semipermeable blood brain barrier (BBB) which is comprises of brain microvascular endothelial cells connected by tight junctions. For NSCLC, chemothereutic approaches also have some limitations such as invasive nature and reoccurrence of disease.To enhance bioavailability of drug across BBB and mucus barrier, high dose of drugs is being used which enhances offsite toxicity risk. To reduce offsite toxicity and enhance bioavailability of these drugs biodegradable nanoparticles (<100 nm size) are being developed as carriers to increase high payload of drugs and release drugs in sustained manner thus reduce dose dependent toxicity. Based on previous reports, current project is designed to synthesize and characterize biodegradable nanoparticles for enhanced bio-distribution. First, different biological materials (lipids, Albumin and PLGA), already being used for nanoparticles (NPs) synthesis were optimized and screened to get 100nm sized nanoparticles with high payload of drugs. PLGA and BSA NPs were selected from all due to high payload of drug 5% of PLGA and (9.5%) in BSA compared to other NPs. Both PLGA-PEG and BSA NPs were further characterized to determine morphology and size using zetasizer, TEM. Release kinetics and in vitro anticancer activity of nanoparticles vs free drug was determined against GBM cell lines (F98, (9LL) and NSCLC cell lines (A549) using toxicity assays. Drug loaded NPs showed promising results, released drugs in sustained manner and retained their toxicity. For GBM, BSA formulations were further characterized for in vivo bio distribution in rats and mice brains tissues by convection enhanced delivery (CED) and systemic delivery using fluorescent and confocal microscope. Conventional Polystyrene (PS) and freshly PEGylated PS particles of 40-60nm size were used as standard.Data was analyzed using MATLAB and statistical softwares (GraphPad Prism and Kaleidagraph). Both empty and drug loaded BSA NPs showed highest ex-vivo and in vivo distributions compared to conventional PS-NPs. BSA NPs were successfully synthesized with high payload of both drugs which retained their activity and release drugs in sustained manner. BSA NPs further showed promising in vivo distribution results both locally and systemically compared to conventional particles of same characteristics already available in market.