کتب سماویہ اور انسانی فکر کا ارتقاء ایک علمی و تحقیقی جائزہ

Allah has created human being and gave him the power of intellectual understandings. To utilize and make positive use of this Allah sent Holy books for guidance. While, keeping the sequence of these books and the historical evolution of human mind, one can easily recognize the symmetrical progress in both. Human starts living in caves and through his intelligence created homes to live, tools to gain meal, and so on, till todays growth. As far as, evolution of Holy books is considered, Scriptures were revealed in different portions as human at that stage couldn’t write or store on pages or another source. Old Testament was revealed earlier. It is combination of Torah, Psalms and other books. In the context of Islam, Torah was the first book revealed on Hazrat Mosa, in which commandments were given as per the level of Bani Israel. Afterwards, Psalms, containing poetic way inspires Bani Israel after the Torah and the Bible Last Holy book in the generation of Israel, comprises of observational and experiential way, as required in that era. Holy Quran, compiled and final version of all the past version, is summary and elemental book. In which, descriptive, observational, experiential, poetic, logical, argumentative and comprehensive technique are present. These all shows, ultimate intellectual growth of human is being address in Holy Quran. As Human is now intellectually at its peak so the teaching and techniques used are at highest level of literature, showing the step by step evolution and association of Holy books with Human being.

Formulation and Evaluation of Macrophage Targeted Thiolated Nanocarriers for the Enhanced Efficacy of Anti-Leishmanial Drugs

The present study was designed to synthesize some innovative multifunctional polymeric excipients for improved efficacy and site-specific delivery of antiLeishmanial drugs. Therefore, mannose anchored thiolated chitosan-graftedpolyethyleneimine (M-(CS-g-PEI)-TGA) polymeric excipient was synthesized and utilized for the development of first-line Meglumine Antimoniate (MA) antiLeishmanial drug nanoformulation to address the cellular bioavailability limitations. On the other hands, mannose anchored thiolated chitosan (M-CS-TGA) polymeric excipient was manufactured for the production of second-line Amphotericin B (AmB) anti-Leishmanial drug nanoformulation to reduce off-target adverse events by specific pathological organs reservoirs delivery. The newly synthesized M-(CS-g-PEI)-TGA polymeric excipient graft was evaluated for Trypanothione Reductase (TR) enzyme inhibition as a potential target. The observed hydrodynamic size of M-(CS-g-PEI)-TGA based MA nanoformulation and M-CS-TGA based AmB nanoformulation was found to be 287 ± 20 and 482 ± 17 respectively, with positive zeta-potential and low PDI. M- (CS-g-PEI)-TGA based MA nanoformulation showed the maximum macrophage internalization uptake of 61.47 ± 0.25 µg/106 cells. The flow cytometry analysis against Leishmania donovani infected macrophage model demonstrated 7.9- and 23-folds enhanced efficacy of M-(CS-g-PEI)-TGA based MA nanoformulation and M-CS-TGA based AmB nanoformulation as compared to MA and AmB, respectively. The results of in-vivo BALB/c mice visceral Leishmaniasis model for M-(CS-g-PEI)-TGA based MA nanoformulation displayed 5.22-fold decreased parasitic burden (p < 0.0001) compared to that of MA. For maximum selective targeting of the pathological organ while minimizing exposure to the organs prone to toxic effects, in vivo tissue distribution study, was conducted. M-CS-TGA based AmB nanoformulation showed a higher concentration of AmB (101 mg) in the liver as compared to the native AmB drug (43 mg). But in the case of the kidney, the M-CS-TGA based AmB nanoformulation revealed less concentration of AmB with respect to native AmB drug. Inorder to establish the safety profile of the AmB nanoformulation, the acute oral toxicity in female Swiss mice did not show any evident change in cellular morphology supporting the safety of M-CS-TGA due to renal clearance. The oral pharmacokinetic studies showed that M-(CS-g-PEI)-TGA based nanoformulation and M-CS-TGA based nanoformulation significantly enhanced bioavailability of MA and AmB respectively. The observed enhanced pharmacokinetic profile might be due to permeation enhancing potential of synthesized polymeric excipients. Based on these findings, incorporation of new multifunctional polymeric excipients for the development of macro phage targeted nano formulation seems to be a promising strategy to enhance the efficacy and safety of the anti-Leishmanial drug.