diff --git a/Taxol.svg b/Taxol.svg new file mode 100644 index 0000000..ba7ba0b --- /dev/null +++ b/Taxol.svg @@ -0,0 +1,125 @@ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + diff --git a/coursework.lyx b/coursework.lyx index c3574a2..5d9f981 100644 --- a/coursework.lyx +++ b/coursework.lyx @@ -216,7 +216,7 @@ status open \begin_inset Graphics filename WellBandStructure.png lyxscale 40 - width 60col% + width 50col% \end_inset @@ -1422,7 +1422,7 @@ status open \begin_inset Graphics filename probability-plot.png lyxscale 30 - width 75col% + width 60col% \end_inset @@ -1468,7 +1468,7 @@ status open \begin_inset Graphics filename probability-plot-with-n-2.png lyxscale 30 - width 75col% + width 60col% \end_inset @@ -1613,7 +1613,7 @@ status open \begin_inset Graphics filename probability-plot-with-bounds.png lyxscale 30 - width 75col% + width 60col% \end_inset @@ -1751,7 +1751,7 @@ Considering these two probabilities it is clear that it is more likely for the electron to be found between 6nm and 8nm than between 2nm and 4nm across the well. This is as expected considering 6nm to 8nm places the interval towards - the center of the well. + the center of the 14.87nm well. As the probability density function is a \begin_inset Formula $\sin^{2}$ \end_inset @@ -1786,26 +1786,208 @@ Application of Nanomaterials \begin_layout Standard The use of albumin protein nanoparticlces has provided a new delivery method for the highly effective chemotherapy drug, paclitaxel, in turn reducing - side effects caused by previous delivery schemes and increasing circulation - half life around the body. + side effects and toxicity caused by previous delivery schemes and increasing + circulation half life around the body. \end_layout \begin_layout Section Paclitaxel \end_layout -\begin_layout Section -Previous Delivery +\begin_layout Standard +Paclitaxel is a chemotherapy drug in the taxane family which function as + mitotic inhibitors. + This involves the suppression of mitosis or cell division which is effective + in treating cancer as constant cell mitosis is how cancer spreads throughout + the body. +\end_layout + +\begin_layout Standard +While taxanes are an effective cancer treatment, their use has proved difficult + as they are not particularly soluble in water requiring a delivery vehicle + in order to allow intraveneous application. +\end_layout + +\begin_layout Standard +\begin_inset Float figure +wide false +sideways false +status open + +\begin_layout Plain Layout +\align center +\begin_inset Graphics + filename Taxol.svg + lyxscale 30 + width 30col% + +\end_inset + + +\end_layout + +\begin_layout Plain Layout +\begin_inset Caption Standard + +\begin_layout Plain Layout +Chemical structure for paclitaxel +\end_layout + +\end_inset + + +\end_layout + +\begin_layout Plain Layout + +\end_layout + +\end_inset + + \end_layout \begin_layout Section -Albumin +Previous Delivery Methods +\end_layout + +\begin_layout Standard +As a result of the poor water solubility of taxanes and paclitaxel, a method + for delivering a solution was required. + Polyethoxylated castor oil (commercially known as Kolliphor EL, formerly + Cremophor EL [CrEL]) combined with dehydrated ethanol provides a suitable + formulation vehicle for many poorly water soluble and has been the standard + for many forms of commercially available paclitaxel such as Taxol. +\end_layout + +\begin_layout Standard +While this solution has proved to be an effective delivery mechanism there + are significant side effects. + CrEL has been shown to cause severe hypersensitivity reactions and peripheral + neuropathy which are exacerbated by the high volumes of delivery agent + which must be coadministered with the active ingredient +\begin_inset CommandInset citation +LatexCommand cite +key "elsevier_sdoi_10_1016_S0959_8049_01_00171_X" +literal "false" + +\end_inset + +. + The use of CrEL also affects the behaviour of paclitaxel when administered, + manifesting as undesirable non-linear absorption, distribution, metabolism + and excretion behaviour +\begin_inset CommandInset citation +LatexCommand cite +key "proquest78006535" +literal "false" + +\end_inset + +, typically referred to as a drug's pharmacokinetic characteristics. +\end_layout + +\begin_layout Section +Human Serum Albumin +\end_layout + +\begin_layout Standard +Human serum albumin (HSA), sometimes referred to as blood albumin is the + most frequently found protein in the human body +\begin_inset CommandInset citation +LatexCommand cite +key "proquest1881262578" +literal "false" + +\end_inset + + and is part of the albumin family of proteins. + HSA is produced by the liver and performs important functions such as maintaini +ng oncotic pressure in the blood vessels, ensuring the right levels of fluids + are found between blood vessels and body tissues, and transporting hormones + and fatty acids around the body. + +\end_layout + +\begin_layout Standard +\begin_inset Float figure +wide false +sideways false +status open + +\begin_layout Plain Layout +\align center +\begin_inset Graphics + filename hsa.jpg + lyxscale 30 + width 40col% + +\end_inset + + +\end_layout + +\begin_layout Plain Layout +\begin_inset Caption Standard + +\begin_layout Plain Layout +Crystal structure of human serum albumin with binding sites annotated +\begin_inset CommandInset citation +LatexCommand cite +key "BARBOSA2014345" +literal "false" + +\end_inset + + +\end_layout + +\end_inset + + +\end_layout + +\begin_layout Plain Layout + +\end_layout + +\end_inset + + +\end_layout + +\begin_layout Standard +Importantly for the application of drug delivery HSA along with the rest + of the albumin proteins are water soluble and HSA effectively binds with + both hydrophobic and hydrophilic chemicals +\begin_inset CommandInset citation +LatexCommand cite +key "proquest1881262578" +literal "false" + +\end_inset + +. + Critically HSA has been shown to be nontoxic, non-immunogenic (provokes + little response from the immune system), biocompatible and biodegradable +\begin_inset CommandInset citation +LatexCommand cite +key "wos000301045400002" +literal "false" + +\end_inset + + providing many advantages over Cremophor EL delivery. \end_layout \begin_layout Section NAB-Paclitaxel \end_layout +\begin_layout Standard +Word Count: +\end_layout + \begin_layout Standard \begin_inset Newpage pagebreak \end_inset diff --git a/coursework.pdf b/coursework.pdf index 58d0a29..cab6c3a 100644 Binary files a/coursework.pdf and b/coursework.pdf differ diff --git a/hsa.jpg b/hsa.jpg new file mode 100644 index 0000000..4199c04 Binary files /dev/null and b/hsa.jpg differ diff --git a/references.bib b/references.bib index c0b7de0..3adeac6 100644 --- a/references.bib +++ b/references.bib @@ -15,6 +15,7 @@ year = "2014-11" @misc{new_semiconductor_materials_archive, title={NSM Archive - Physical Properties of Semiconductors}, +author={IoffeInstitute}, url={http://matprop.ru/}, journal={New Semiconductor Materials Archive}, publisher={Ioffe Institute} @@ -78,5 +79,74 @@ volume = "55", year = "1989-08-14", } +@article{elsevier_sdoi_10_1016_S0959_8049_01_00171_X, +author = "Gelderblom, H and Verweij, J and Nooter, K and Sparreboom, A", +issn = "0959-8049", +journal = "European Journal of Cancer", +keywords = "Cremophor El ; Formulation Vehicles ; Paclitaxel ; Pharmacokinetics ; Pharmacodynamics ; Medicine", +language = "eng", +number = "13", +pages = "1590,1598", +publisher = "Elsevier Ltd", +title = "Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation", +volume = "37", +year = "2001-09", +} + +@article{proquest78006535, +author = "Sparreboom, A and van Tellingen, O and Nooijen, W J and Beijnen, J H", +issn = "0008-5472", +journal = "Cancer research", +keywords = "Animals–Pharmacokinetics ; Antineoplastic Agents, Phytogenic–Analogs & Derivatives ; Chromatography, High Pressure Liquid–Pharmacokinetics ; Dose-Response Relationship, Drug–Pharmacokinetics ; Female–Pharmacokinetics ; Glycerol–Pharmacokinetics ; Humans–Pharmacokinetics ; Mice–Pharmacokinetics ; Paclitaxel–Pharmacokinetics ; Pharmaceutical Vehicles–Pharmacokinetics ; Solvents–Pharmacokinetics ; Antineoplastic Agents, Phytogenic ; Pharmaceutical Vehicles ; Solvents ; Cremophor El ; Paclitaxel ; Glycerol", +language = "eng", +number = "9", +pages = "2112,2115", +title = "Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL.", +url = "http://search.proquest.com/docview/78006535/", +volume = "56", +year = "1996-05-01", +} + +@article{proquest1881262578, +author = "Lomis, Nikita and Westfall, Susan and Farahdel, Leila and Malhotra, Meenakshi and Shum-Tim, Dominique and Prakash, Satya", +issn = "2079-4991", +journal = "Nanomaterials (Basel, Switzerland)", +keywords = "Mcf-7 ; Cancer ; Human Serum Albumin ; Nanoparticles ; Paclitaxel", +language = "eng", +number = "6", +title = "Human Serum Albumin Nanoparticles for Use in Cancer Drug Delivery: Process Optimization and In Vitro Characterization.", +url = "http://search.proquest.com/docview/1881262578/", +volume = "6", +year = "2016-06-15", +} + +@article{wos000301045400002, +author = "Elzoghby, Ao and Samy, Wm and Elgindy, Na", +issn = "0168-3659", +journal = "Journal Of Controlled Release", +language = "English", +number = "2", +pages = "168,182", +publisher = "ELSEVIER SCIENCE BV", +title = "Albumin-based nanoparticles as potential controlled release drug delivery systems", +volume = "157", +year = "2012-01-30", +} + +@incollection{BARBOSA2014345, +title = "Chapter 32 - Fibrillation and Polymorphism of Human Serum Albumin", +editor = "Vladimir N. Uversky and Yuri L. Lyubchenko", +booktitle = "Bio-nanoimaging", +publisher = "Academic Press", +address = "Boston", +pages = "345 - 362", +year = "2014", +isbn = "978-0-12-394431-3", +doi = "https://doi.org/10.1016/B978-0-12-394431-3.00032-8", +url = "http://www.sciencedirect.com/science/article/pii/B9780123944313000328", +author = "Silvia Barbosa and Pablo Taboada and Víctor Mosquera", +keywords = "human serum albumin, misfolded states, downhill polymerization, nucleation, lag phase, structural intermediates, curly fibrils, polymorphism, spherulites, biohybrid materials", +abstract = "Protein misfolding and self-assembly of disease-related and disease-unrelated proteins and peptides into highly ordered β-sheet-rich amyloid fibrils converts this self-assembly pathway in a ‘generic property’ of polypeptide chains. Hence, to gain a detailed knowledge about the underlying packing and fibrillation mechanisms of such a process the use of model proteins appears to be the key. Human serum albumin (HSA) appears to be an excellent candidate because it is highly abundant and plays fundamental biologic roles; it also displays a complex tertiary structure without any propensity to fibrillation in its native state. Thus, in this chapter, we first give a very brief summary of the main aspects of the origin of protein fibrillation. Subsequently, we describe how the various factor induce HSA fibrillation, and we also describe the possible aggregation pathways and the structure of the resulting fibrils." +}