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Microemulsions for the Encapsulation of Drugs and Recovery of Metal Nanoparticles

Thesis Info

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Author

Nazar, Muhammad Faizan

Program

PhD

Institute

Quaid-I-Azam University

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2011

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/handle/123456789/1646

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726642132

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The work reported in the present thesis covers various investigations carried out under microemulsion conditions. More specifically it includes the encapsulation of nonsteroid anti- inflammatory drug (piroxicam) and the preparation and recovery of cetyltrimethylammonium chloride (CTACl) capped metal nanoparticles (Au, Pd, SiO2). Microemulsions are colloidal self-assembly fluids, function as nanoreactors and are suitable replacement for enhancing the loading capacity of drugs and recovery of nanoparticles. It was found that high loading capacity of piroxicam (1 wt%) and paramount recovery of nanoparticles (upto 98%) highlight the proficiency of the microemulsions in pharmaceuticals and in separation science. Microemulsion in this thesis has been used for encapsulation of anti-inflammatory drug (piroxicam). The results have demonstrated the absolute stability of microemulsion formulation after the incorporation of piroxicam. The main objective of this study was the development of rapid oil-in-water microemulsion to improve the loading capability of pharmaceutical compound in highly hydrophobic formulation. Tween-80 based microemulsion was successfully utilized to encapsulate and to enhance the solubility of piroxicam. In the present work various rheological and the spectroscopic analyses were employed to explore the gradual changes occurring in the microstructure of microemulsion. In addition, the consequence of piroxicam incorporation on the stability, optical consistency and microstructure of microemulsion formulation was also accomplished. Investigations into the stability of microemulsion under milder conditions showed that it remained clear and transparent over 10 months. During the project a special type of microemulsion was also developed that may make the recovery, recycling and reuse of nanoparticles easier for the manufacturers. The synthesis of nanoparticles in microemulsion systems has recently become an important focus of research. The inverse microemulsion (water-in-oil) technique has been successfully utilized to synthesize colloidal nanoparticles of inorganic materials. In the project a new approach towards the synthesis of gold nanoparticles (Au-NPs) in a reverse microemulsion was established and ‘at the flick of a switch’ water-induced separation route was employed for their recovery. Water-in-oil microemulsions (w/o MEs) stabilized by the cationic surfactant CTACl have been used as reaction media to generate Au-NPs. In addition the pure MEs have also been used as dispersion media for those Au and Pd-NPs, which have been pre- synthesized in aqueous phases and stabilized by sodium 2-mercaptoethanesulfonate (MES) ligands, and commercially available SiO2-NPs. A general method for recovery and separation of the nanoparticles from these mixed NP-ME systems has been demonstrated by tuning phase behavior of the background microemulsions. Addition of appropriate aliquots of water drives a clean liquid-liquid phase transition, resulting in two macroscopic layers, the NPs preferentially partition into an upper oil-rich phase and are separated from excess surfactant which resides in a lower aqueous portion. In order to assemble the detailed quantitative and qualitative outcomes of nanoparticles, UV-vis spectroscopy and transmission electron microscopy (TEM) were developed respectively. For instance, ~90% of the microemulsion prepared Au-NPs can be recovered; with even greater separation efficiencies attainable for pre-synthesized MES stabilized Au-MES-NPs (~98%) and Pd-MES-NPs (92%). For the silica NP-ME dispersions gravimetry indicates ~ 84% recovery of the NPs. TEM images of all systems showed that NP shapes and size distributions were generally preserved after these phase transfer processes. This low-energy and cost-effective purification route appears to be a quite general approach for processing inorganic NPs, having advantages of being isothermal, using only commercially available inexpensive components and requiring no additional organic solvents.
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Bioinformatics and Experimental Analysis of the Genetic and Non-Genetic Basis of Breast Cancer in Pakistani Population

Breast cancer is a multifactorial and complex disorder. It is posing serious public health concerns and its incidence rate is on the rise in Pakistan. It is therefore of prime importance to identify genetic and/or non-genetic factors contributing towards the development and progression of breast cancer. The present investi gation is a case-control study including 1000 cases and 1000 age matched con trols of the same ethnic background. Individuals were recruited on the basis of a predefined inclusion and exclusion criteria. All participants were in-person di rectly interviewed after signing an informed consent document. Peripheral blood samples were collected from all the participants along with personal identifiers, demographic characteristics and family history of cancer and other diseases. Vital status/survival status of the patients was determined for up to a maximum of 47 months to record the censored data. We analyzed our sequenced variants and clinico-pathologic features for their possible association with the disease risk by using unconditional logistic regression. Association of the variables was measured with ORs and corresponding 95% confidence intervals. Overall survival of the patients was assessed using Kaplan-Meier curve. Cox proportional hazard model was used to calculate risk ratios and to adjust for potential confounders. A total of thirteen variants were reported in BRCA1 and BRCA2 genes respec tively including three novel variants (Exon3 -37insC, Exon3 -215T<C and Exon14 102-103insTC) in BRCA1 and five novels (exon8 +87insA, exon20 +318T<A, exon19 -351-353delTCT, exon16 -17G<T and exon27 T129A) in BRCA2. Five out of thirteen variants were the in silico identified, HapMap confirmed, pathogenic and previously reported in other populations. Their contribution towards disease risk was tested in our sampled population and it was observed that rs28897686 polymorphism of BRCA1 and rs28897743 of BRCA2 were observed positively asso ciated, while rs28897696 and rs1060915 polymorphisms of BRCA1 and rs4987049 SNP of BRCA2 were found not associated with the disease risk. Five of the eight novel variants, two in BRCA1 (-37insC exon 3 and 102-103insTC exon 14) and three in BRCA2 (+87insA exon 8, -351-353delTCT exon 19 and T129A exon 27) xii were observed only in the breast cancer cases and found completely absent in the controls while the rest of 3/8 of the novel variants (BRCA1 -215T<C exon 3, BRCA2 +318T<A exon 20 and BRCA2 -17G<T exon 16) were found highly significantly associated with breast cancer risk. Pairwise Linkage Disequilibrium analysis showed that the strong LD (D0=0.52) exists in between rs28897696 and -215T<C exon 3 variant of BRCA1 and LD (D0=0.43) in between rs28897743 and -17G<T exon 16 of BRCA2. We also examined the cross-sectional associations of life style, reproductive and socio-demographic risk factors with breast cancer density in Pakistani women. Mean age of cases and controls at recruitment was 50.58±10.68 and 54.78±14.52 years while mean BMI for cases and controls was 26.07±4.04 and 25.05±4.25, respectively. Among the patients 60.70% were married, 46.50% were nulliparous, 16.90% had≥4 children, 39.90% women breast fed their children, 88.90% were nonsmokers and 67.90% were physically active. Post-menopausal women diagnosed with breast cancer accounted for 52.30%. In the current data set, 31.70% patients had at least a blood relative diagnosed with some type of cancer, 22.80% patients were diagnosed with other types of medical complications including high blood pressure, diabetes etc. Significant association between age and breast cancer was observed. Overweight (BMI≥25) and obese (BMI≥30) females have approximately 1.5 times more risk of having breast cancer (Overweight; OR = 1.52, 95% CI: 1.28-1.81 and Obese; OR = 1.41, 95% CI: 1.14-1.74). It was also observed that unmarried women were at more than two fold higher risk. Similarly use of oral contraceptives and smoking were also significantly associated with increasing risk of breast cancer. Individuals who were physically inactive were recorded to be 1.27 times more likely to develop breast cancer. We have found approximately 1.34 fold increase in the disease risk among the postmenopausal patients (OR = 1.34, 95% CI: 1.14-1.58). Breast cancer patients were observed having an overall median survival time of 33 months (95% CI: 28-34). In this present study we attempted to define the genetic and non-genetic basis responsible for breast cancer incidence among Pakistani population. It can be concluded that there is a significant contribution of BRCA1 and BRCA2 genetic alterations in breast cancer pathogenesis. It is hoped that our findings will be of great importance to establish adequate evidence-based awareness and preventative measures against breast cancer in Pakistani women.