Search or add a thesis

Advanced Search (Beta)
Home > Synthesis and Characterization of Drug Loaded Biodegradable Nanoparticles for Enhanced Bio-Distribution

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

Thesis Info

Access Option

External Link

Author

Umara Afzal

Program

PhD

Institute

Pir Mehr Ali Shah Arid Agriculture University

City

Rawalpindi

Province

Punjab

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Biochemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/10994/1/Umara%20Afzal_Biochem_2019_PMAS_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727445684

Similar


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.
Loading...
Loading...

Similar Books

Loading...

Similar Chapters

Loading...

Similar News

Loading...

Similar Articles

Loading...

Similar Article Headings

Loading...

اداسی کی برکھا میں بھیگی شاعری

اداسی کی برکھامیں بھیگی شاعری
میر اور ناصر کی شعری کائنات سے محمد ندیم صادق نے اپنے لگائو کا ثبوت ’’جگر خوں کروں ہوں میں‘‘کی صورت میں فراہم کیا ہے۔اس مجموعے میں شامل غزلیں اور نظمیںایک ہی کتھا سنا رہی ہیں۔خوف، اداسی، تنہائی اور نارسائی میں گندھی بیدار راتوں کی کتھا۔
دل میں کیسا خوف بھرا ہے
پھول کھلے تو ڈر لگتا ہے
رات گئے تک ان گلیوں میں
کوئی آوارہ پھرتا ہے
کلی جو کھل کر پھول بنی تھی
پھول کسی نے توڑ لیا ہے
مندرجہ بالا اشعار جس کیفیت کی عکاسی کر رہے ہیں اسے قنوطیت سے تعبیر کیا جا سکتا ہے مگر کسی روشن تخلیقی لمحے میںشاعر نے اس فضا سے باہر نکلنے کا راستا، خوش کن یادوںاور فطرت کے حسن سے وابستگی کی صورت میںتلاش کیا ہے۔
یادوں کی بارش میں صادق
کب سے بیٹھا بھیگ رہا ہے
ساغر میں اک پھول کھلا ہے
سارا جنگل مہک اُٹھا ہے
سادگی اور لہجے کی دھیمی آنچ نے جذبے کے خالص پن کولفظوں کے بنائو سنگھار میں گم نہیں ہونے دیا۔حسّیاتی رنگ و آہنگ میں ڈھلی امیجری اور معروضی تلازمات بھی داخلی کیفیات کے ہی عکاس ہیں۔
شہر کی سڑکیں تو ٹھنڈی ہیں
لیکن میرا دل جلتا ہے
پیار محبت کرنے والا
کورا کاغذ پڑھ سکتا ہے
تیرے شہر میں آ کر مجھ کو
اپنا آپ ہی بھول گیا ہے
میر نے (۳۰ رکنی ہندی بحر)میں درجنوں لاجواب غزلیں کہی ہیں اور ناصر نے (۱۶ رکنی ہندی بحر) کا مسحور کن تجربہ کیا ہے۔اس بحرِ ہزار موج کے اتار چڑھائومیں دلی کیفیات کازیروبم خوب محسوس کیا جا سکتا ہے۔ بید ِ مجنوں کی سی لچکیلی یہ مترنم بحرتربیت یافتہ قاری پر اپنا جادو خوب جگاتی ہے۔ندیم صادق نے ناصر کی تقلید میں اس بحر کو اختیار کیا ہے۔
یقیناکچھ مقامات پر عروض ، داخلی آہنگ...

Water Sharing Conflicts and Management in the Indus River Basin

Sharing water resources within country and amongst transborder countries often create conflict because of increasing demand of fresh water for their domestic, industrial and agricultural sectors due to growing population and increasing economic activities. As a result, every country is interested to build more water storages like dams and barrages to safeguard their water requirements in the lean periods or to protect their areas during flood period. Therefore, a transboundary conflict amongst riparian countries on water sharing is obvious facts which are resolved either through bilateral dialogue or by involving international arbitrators. Similarly, a conflict of water sharing within a country has also been serious issue particularly during drought and lean period resulting political conflicts and obstacles in construction of dams and reservoirs. Pakistan is country of 207 million populations, the sixth of the most populated country of the world has been facing transboundary water sharing conflict with India while within a country inter provinces mistrust over water distribution has created reservation over the construction of new water storages. Pakistan has two agreements which provide legal framework for water distribution and management. Indus Water Treaty is an international agreement signed in 1960 between India and Pakistan and other is national agreement amongst the provinces called Indus water accord signed in 1991 by province. Despite several reservations and hostile territorial conflicts between India and Pakistan the Indus water treaty has been successfully functioning in managing water distribution of Indus River and its eastern tributaries originate from Indian occupied Kashmir. Similarly, Indus water accord 1991 provides a mechanism to resolve water sharing conflicts amongst provinces.

Laboratory and Field Evaluation of a Locally Prepared Montanide Adjuvanted Combined Hemorrhagic Septicemia-Mastitis Vaccine.

The present study represents a maiden attempt to develop and evaluate a combined hemorrhagic septicemia (HS) and mastitis vaccine in cows and buffaloes. The study was compartmentalized into two phases. In phase I (laboratory settings), isolates of Pasteurella multocida, Staphylococcus aureus and Streptococcus agalactiae recovered from field cases of HS and mastitis were scrutinized for virulence/pathogenicity and immunogenicity in laboratory animals. Bacterin- toxoids of S. aureus and Str. agalactiae were blended with prepared antigen of P. multocida, Montanide® ISA 201 VG, thimerosal and sodium azide to prepare combined HS- mastitis vaccine that was evaluated for sterility, safety and side effects underin vitro conditions/in cattle, buffaloes and mice. A challenge-protection assay conducted in immunized mice indicated 100% survival of challenged mice. The vaccine was physically stable in terms of pH, sedimentation, color, appearance, and syringibility for 6 months observation period at 37°C. In Phase II (field evaluation), the combined vaccine was evaluated in cows, buffaloes and calves. To this end, a total of 70 S. aureus and Str. agalactiae free lactating buffaloes (n=45) and cows (n=25), 50 lactating cows (n=25) and buffaloes (n=25) positive for S. aureus/Str. agalactiae and dairy calves (buffalo calves n=70; cow calves n=50) aged up to 1 year were treated with 2 doses of combined HS-mastitis vaccine at 21 day interval and evaluated (where relevant) for 6 months in terms of ELISA based antibody titers against P. multocida, S. aureus and Str. agalactiae, incidence of HS, local and systemic reactions, incidence and prevalence of S. aureus and Str. agalactiae mastitis, severity of mastitis, milk somatic cell count, milk yield, cost effectiveness and vaccine efficacy. ELISA based antibody titers against P. multocida, S. aureus and Str. agalactiae were higher in vaccinated groups than in un-vaccinated groups. Two cases of HS were recorded in vaccinated animals vis-à-vis 7 cases in un-vaccinated animals. Incidence of S. aureus and Str. agalactiae over 180 days in vaccinated and un-vaccinated cows and buffaloes initially cultural –ve for these pathogens was 3 and 10, respectively; the corresponding figures in groups initially culture +ve for these pathogens being 2 and 12, respectively. Cumulative mean somatic cell counts in vaccinated groups were significantly lower (P>0.05) than those in respective unvaccinated controls. Milk yield was significantly higher (P<0.05) in vaccinated cows and buffaloes than in un-vaccinated controls. Mastitis severity scores were lower in vaccinated groups than in un-vaccinated controls. The vaccine tested had a vaccine efficacy 84.78 and 90.25% against HS and mastitis, respectively with a financial benefit worth Rs 2,060,300. In sum, Montanide® adjuvanted combined HS-mastitis vaccine had preventative role against HS and both preventative and curative role against S. aureus and Str. agalactiae associated mastitis. In view of the preliminary nature of the study, additional work involving much larger number of cows, buffaloes and calves is clearly warranted.