The principal goal of this research is to achieve the chemical labeling and surface modification of block copolymer vesicles (polymersomes) made from amphiphilic diblock copolymer Poly(butadiene-b-ethylene oxide) (PBd120- PEO89, MW 10400 g/mol) with the aim of developing possible drug carrier vehicles for controlled release of molecules triggered by stimuli-responsive environments. The terminal hydroxyl group of poly(ethylene oxide) (PEO), or poly(ethylene glycol) is converted into its corresponding carboxylic acid by a novel one-pot two-phase oxidation reaction. This regioselective and catalytic reaction assures the preservation of important structural characteristic of the block copolymers. Vesicles formed by a mixture of the carboxylate and unmodified block copolymer exhibit an increment in the critical aggregation concentration (CAC) value while the averaged vesicle size decreases demonstrating that the negative charges in the modified diblock copolymer disrupt the vesicle formation process. The carboxylated reactive intermediates are subsequently subjected to a covalent coupling reaction in organic solvent to replace the terminal hydroxyl of the PEO block. The obtained functionalized diblock copolymers are effectively incorporated into the vesicle bilayer. Also, surface density control in polymersomes of fluorescently modified diblock copolymers, synthesized by the amination reaction, is achieved. To demonstrate the ability of this polymersomes as carrier vehicles, a Noradrenaline functionalized vesicle is placed in closed contact with rat aortic smooth muscle cells (RASMC) using the micropipette aspiration technique. A distinctive increase in fluorescent intensity of cells is observed. It indicates that the drug molecule has been transported by the polymersome and internalized by the cell. In addition, diblock copolymers containing a disulfide moiety and a fluorophore are synthesized and studied through fluorescent microscopy. Vesicles are formed with this polymer and a decrease in fluorescent intensity is observed in the vesicle's bilayer after its exposure to a reductive environment. These results indicate that fluorophore molecules are successfully released into solution.

The skin forms an attractive and accessible route for systemic delivery of drugs as alternative to other methods of administration, such as the oral and parental methods because of the problems associated with last mentioned methods. The lipophilic character of the stratum corneum, coupled with its intrinsic tortuosity, ensures that it almost always provides the principal barrier to the entry of drug molecules into the skin. Due to the fact that methotrexate (MTX) and acyclovir (ACV) have poor penetration properties through the skin, the aim of this study was to enhance the permeation of methotrexate and acyclovir with the use of two lamellar gel phase systems (LPGS) (Physiogel® NT and Physiogel® Dermaquadrille) and with Emzaloid® as transdermal drug delivery systems. Three different sets of experiments were done in this study: 1) the viscosity of the two Physiogel® creams was measured as an indication of stability and to determine whether the internal structure of the Physiogel® creams were affected by the investigated drugs; 2) the drug release rate from the three drug delivery vehicles was measured with a Vankel ® dissolution apparatus; 3) in vitro permeation studies were preformed using vertical Franz diffusion cells with human epidermal skin clamped between the donor and receptor compartments. The skin was hydrated with PBS buffer for one hour before 1% mixtures of the drugs in both the Physiogel® creams and Emzaloid® were applied to the donor chamber. Samples were taken at 2, 4, 6, 8, 10, 12 and 24 hours. It was then analysed by HPLC for methotrexate and acyclovir. The fluxes of drug permeation were determined. The viscosity measurements confirmed that the internal structure of the two Physiogel® creams was not influenced by the drugs. Acyclovir and methotrexate were both released from the delivery vehicles. There was an enhancement of acyclovir through the skin from one of the Physiogel® creams. The permeability of methotrexate in the presence of the two Physiogel® vehicles was not significantly enhanced. Emzaloid® as delivery vehicle increased the penetration of both drugs through the skin significantly. The lamellar gel phase system mimics the structure of the stratum corneum, but does not improve the drug permeation through the stratum corneum significantly. The utilisation of Emzaloid® as a drug delivery system could be advocated from these findings. As could be seen from the penetration profiles Emzaloid® was a superior delivery system for methotrexate and acyclovir compared to the lamellar gel phase systems. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

The skin forms an attractive and accessible route for systemic delivery of drugs as alternative to other methods of administration, such as the oral and parental methods because of the problems associated with last mentioned methods. The lipophilic character of the stratum corneum, coupled with its intrinsic tortuosity, ensures that it almost always provides the principal barrier to the entry of drug molecules into the skin. Due to the fact that methotrexate (MTX) and acyclovir (ACV) have poor penetration properties through the skin, the aim of this study was to enhance the permeation of methotrexate and acyclovir with the use of two lamellar gel phase systems (LPGS) (Physiogel® NT and Physiogel® Dermaquadrille) and with Emzaloid® as transdermal drug delivery systems. Three different sets of experiments were done in this study: 1) the viscosity of the two Physiogel® creams was measured as an indication of stability and to determine whether the internal structure of the Physiogel® creams were affected by the investigated drugs; 2) the drug release rate from the three drug delivery vehicles was measured with a Vankel ® dissolution apparatus; 3) in vitro permeation studies were preformed using vertical Franz diffusion cells with human epidermal skin clamped between the donor and receptor compartments. The skin was hydrated with PBS buffer for one hour before 1% mixtures of the drugs in both the Physiogel® creams and Emzaloid® were applied to the donor chamber. Samples were taken at 2, 4, 6, 8, 10, 12 and 24 hours. It was then analysed by HPLC for methotrexate and acyclovir. The fluxes of drug permeation were determined. The viscosity measurements confirmed that the internal structure of the two Physiogel® creams was not influenced by the drugs. Acyclovir and methotrexate were both released from the delivery vehicles. There was an enhancement of acyclovir through the skin from one of the Physiogel® creams. The permeability of methotrexate in the presence of the two Physiogel® vehicles was not significantly enhanced. Emzaloid® as delivery vehicle increased the penetration of both drugs through the skin significantly. The lamellar gel phase system mimics the structure of the stratum corneum, but does not improve the drug permeation through the stratum corneum significantly. The utilisation of Emzaloid® as a drug delivery system could be advocated from these findings. As could be seen from the penetration profiles Emzaloid® was a superior delivery system for methotrexate and acyclovir compared to the lamellar gel phase systems. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.