Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractIn 2012 prostate cancer contributed towards 8% (1.1 million cases) of all cancer incidences around the world. This type of cancer is prevalent in men between the ages of 65-79 years old, with 25% of all cases occurring in men younger than 65 years old. Treatments that are currently available for prostate cancer include surgery, hormone therapy, radiation therapy and chemotherapy. These treatment methods are either very invasive or have harsh side effects including diarrhoea, nausea, alter liver function, anaemia and fatigue. A wide range of anti-cancer drugs in use today have very poor physiochemical properties. New knowledge in this area is required to develop an advanced drug delivery system that improves the properties of these drugs. An example is anti-androgenic drugs such as flutamide (FLT) used in hormonal therapy. The disadvantages to FLT are that it has low bioavailability in oral formulations, low aqueous solubility, compliance issues and rapid first pass metabolism. Recent advances in novel drug delivery have led to the formation of controlled release delivery systems using non-toxic polymeric microspheres. These polymeric microspheres encapsulate the active agent improving its bioavailability and compliance, reducing drug toxicity and side effects. The aim of this investigation was to develop a controlled release FLT delivery system in the form of poly (ε-caprolactone) (PCL) microspheres. The study was set out to evaluate the microspheres aesthetics, physicochemical properties and drug release behaviour. A central composite experimental design was employed to evaluate the effect of two process variables, (1) the polymer PCL at three different molecular weights (MW) 80kDa, 65kDa and 10kDa, (2) the surfactant (poly(vinyl alcohol) (PVA) at two molecular weight ranges 13-23kDa and 30-70kDa. Preparing the organic phase consisted of 500mg of PCL and 50mg of FLT being completed dissolved in 10mL chloroform. The inorganic phase was formed by dissolving PVA in deionised water at a 0.5% weight/volume solution. The organic phase was added drop wise into the inorganic phase to create a 1.30 oil/water ratio. The emulsion was homogenised at 5000rpm for 1 minute. The chloroform was rotary evaporated off, followed by centrifugation and being frozen for 24 hours. The scanning electron microscopy (SEM) analysis was carried out with a freeze dried sample of the microspheres. The percentage yield was calculated to see how the sample amount changed with two process variables. Using laser diffraction, the average diameter of microspheres was determined. The percentage encapsulation efficiency (%EE) was carried out by dissolving PCL-FLT microspheres in Sanjit S. Chaggar 1004138 Masters of Philosophy v | P a g e chloroform and ethanol. The solution was centrifuged and the UV-absorbance was recorded at 300nm. The in-vitro drug release was analysed via dissolution, PCL-FLT microspheres were suspended in a dialysis bag and stirred at 100rpm, in a phosphate buffer saline (PBS) solution. The SEM data suggested the PCL 80kDa/ PVA 30-70kDa formulation produced the smoothest and most uniform microspheres with the highest mean percentage encapsulation efficiency at 90.92% ±1.08%. The micrographs showed that as the PCL MW increased from 10kDa to 80kDa the particle size increased from 5.5μm to 8.4μm. Regarding percentage yield the 80kDa/ PVA 13-23kDa FLT loaded formulations produced the most amount of product, averaging at 72.95% ±1.28%. However, after statistical analysis of %EE and product yield there was no significant difference in data between the two MW ranges of PVA (P>0.05). Dissolution results showed PCL 80kDa/ PVA 30-70kDa microspheres to have a maximal release of 80.23% over 16 days with an intial burst release of 15.38% within the first 4 hours of dissolution. This suggested that encapsulted FLT microspheres can be administered less frequently (once every 2 weeks) at a lower dose (50mg), as the release rate (80.23%/ 16 days) of encapsulted FLT is slower than the half life of free FLT (8 hours). Overall the formulation that produced the most ideal microspheres regarding aesthetics, size, yield, encapsulation efficiency and dissolution was the PCL 80kDa/ PVA 30-70kDa formulation. Further studies that can be conducted include transition electron microscopy (TEM) analysis to evaluate the internal components of the PCL-FLT microsphere complex. A co-polymer such as poly(lactic-co-glycolic acid) (PLGA) can be incorparated along side PCL in order to further improve the encapsulation efficiency. Toxicity studies can also be carried out involving prostate cancer cell lines (MTT Assay).
DescriptionA thesis submitted to The University of Wolverhampton for the degree of MASTERS OF PHILOSOPHY Research in Pharmacy