ABSTRACT
Neurodegenerative disorders cause most physical and mental disabilities, and therefore require effective treatment. The blood-brain barrier (BBB) prevents drug molecules from crossing from the blood to the brain, making brain drug delivery difficult. Implantable devices could provide sustained and regulated medication to solve this problem. Two electrolytes (0.3 M oxalic acid and 0.3 M sulphuric acid) were used to anodise Al2O3 nanoporous membranes, followed by a third anodisation in concentrated H2SO4 to separate the through-hole membranes from the aluminium substrate. FTIR, AFM, and SEM/EDX were used to characterise the membranes' structure and morphology. The effects of the anodisation time and electrolyte type on the AAO layer pore density, diameter, interpore distance, and thickness were examined. As a model drug for neurodegenerative disorders, donepezil hydrochloride (DHC) was loaded onto thin alumina nanoporous membranes. The DHC release profiles were characterised at two concentrations using a UV-Vis spectrophotometer. Oxalic acid membranes demonstrated an average pore diameter of 39.6-32.5 nm, which was two times larger than sulphuric acid membranes (22.6-19.7 nm). After increasing the anodisation time from 3 to 5 h, all of the membranes showed a reduction in pore diameter that was stable regardless of the electrolyte type or period. Drug release from oxalic acid-fabricated membranes was controlled and sustained for over 2 weeks. Thus, nanoporous membranes as implantable drug delivery systems could improve neurodegenerative disease treatment.
ABSTRACT
Breast cancer is among the most prevalent tumors worldwide. In this study, in-situ forming implants (ISFIs) containing rosuvastatin calcium were prepared using three types of poly (D, L-lactic-co-glycolic acid) (PLGA), namely, PLGA 50/50 with ester terminal and PLGA 75/25 with ester or acid terminal. Additionally, polydimethylsiloxane (PDMS) was added in concentrations of 0, 10, 20, and 30% w/v to accelerate matrix formation. The prepared ISFIs were characterized for their rheological behaviors, rate of matrix formation, and in-vitro drug release. All the prepared formulations revealed a Newtonian flow with a matrix formation rate between 0.017 and 0.059 mm/min. Generally, increasing the concentration of PDMS increased the matrix formation rate. The prepared implants' release efficiency values ranged between 46.39 and 89.75%. The ISFI containing PLGA 50/50 with 30% PDMS was selected for further testing, as it has the highest matrix formation rate and a promising release efficiency value. Copper-selenium nanoparticles were prepared with two different particle sizes (560 and 383 nm for CS1 and CS2, respectively) and loaded into the selected formulation to enhance its anticancer activity. The unloaded and loaded implants with rosuvastatin and copper-selenium nanoparticles were evaluated for their antibacterial activity, against Gram-positive and negative microorganisms, and anticancer efficacy, against MCF-7 and MDA-MB-231 cell lines. The results confirmed the potency of rosuvastatin calcium against cancer cells and the synergistic effect when loaded with smaller particle sizes of copper-selenium nanoparticles. This formulation holds a considerable potential for efficient breast cancer therapy.