Development of methods for drug release evaluation from advanced nanoporous anodic alumina structures
- Autores: Pankaj Kapruwan
- Directores de la Tesis: Lluís F. Marsal Garví (dir. tes.), Josep Ferré Borrull (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2021
- Idioma: español
- Tribunal Calificador de la Tesis: Josep Pallarès Marzal (presid.), Jordi Sancho i Parramon (secret.), P. A. Postigo (voc.)
- Programa de doctorado: Programa de Doctorado en Tecnologías para Nanosistemas, Bioingeniería y Energía por la Universidad Rovira i Virgili
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
With advancements in drug delivery systems (DDS), the mechanism through which a drug can be delivered to the targeted site can be classified into active and passive systems. Active DDS consists of the processes where drug release is triggered either through chemical modifications (pH or temperature-responsive), enzymatic attachments or through external stimuli (magnetically & sonic controlled). Passive DDS depends on the concentration gradient of the neighbouring medium (phosphate buffer saline) for the controlled release of the drug through the diffusion process.
One of the main problems with the traditional DDS consists of placing the drug into a capsule or pill form. This leads to an immediate release of drug upon contact with the medium thus having no control over the kinetics. In addition, these systems have a mandatory requirement of multiple dosages to be administered to maintain the desired concentration leading to poor patient compliance, and unpreventable solubility of the drug.
The latest trends in the nanomedicine approaches have allowed preparing several advanced structures based on porous materials such as nanoporous anodic alumina (NAA), porous silicon (pSi), and titania for drug delivery technologies. These structures serve as an excellent substitute to the older systems (rubbers and thin films) as they do not degrade easily. Several studies in the past have utilized these structures for loading and monitoring the release with the conventional methods through the collection of multiple sampling and measurement with UV-VIS spectroscopy. However, since the samples are collected at a fixed interval of time, these systems fail to mimic in-vivo dynamic changes inside the body. Therefore, a controlled drug delivery technology is required to gain control over the release of drugs and to understand the release kinetics more conveniently. This thesis put forward an attempt to solve these challenges by studying the release kinetics from advanced structures based on nanoporous anodic alumina using optical technology.
Methodology:
To start working in this direction, several advanced NAA structures i.e. nanoporous anodic alumina gradient-index filters (NAA-GIFs), and Hy-NAA-GIFs (Hybrid nanoporous anodic alumina gradient-index filters) has been prepared with the electrochemical method in oxalic acid under controlled stirring and temperature. To increase the pore size, different pore widening treatments have been performed using phosphoric acid for the desired time interval as well. The aluminium from the bottom has also been removed with the chemical etchant containing hydrochloric acid and copper chloride to see the interferometric color and to improve the contrast of the photonic stopbands (PSB) obtained.
A drop-casting method is an effective procedure to fill the pores. The procedure includes dropping the drug solution on top of the sample followed by the air-dried at room temperature. A total of 6 drops were performed and to understand this filling pattern, the samples were measured by UV-Visible spectroscopy after each consecutive drop. To support the results, the transfer matrix method (TMM) was also done to evaluate the changes in the reflectance spectra of the nanoporous structures during the filling process.
To avoid releasing all the drug at once, alternating layers of polystyrene sulfonate (PSS) and polyallylamine hydrochloride (PAH) were applied through layer by layer deposition method within the structures. Different drug-loaded samples were placed in a flow cell setup connected to reflectance spectroscopy to record the data during the release. When the medium passes through the drug-loaded sample, the software record the changes happening in real-time thus permitting the data to be analyzed. The results gathered were fitted with a model consisting of an exponential function that shows a diffusion-controlled release process from NAA structures.
The main conclusions have been listed below:
1) A modified one-step electrochemical approach was successful in obtaining NAA structures using oxalic acid. A set of samples were prepared followed by the continuous monitoring of temperature and stirring for easy reproducibility.
2) NAA-GIFs has been shown as an excellent optical platform to hold and study the release of a drug. The structure consists of two PSBs, the relative height of which changes upon infiltration and can be correlated directly with the drug present inside them. The critical point to be noted is that one of the PSB falls within the drug absorption region while the other is present far from this absorption range. This allows one to obtain a ratio between the two PSBs that can be related to amount of drug inside the pores. The polyelectrolytes multilayer applied, serve as an excellent modification method to hold the drug molecules inside the structures and allowing to study the release kinetics from porous structures. Reflectance spectroscopy in conjugation with the flow cell setup allows recording the release spectra from NAA-GIFs in real-time while different pH solutions are being flowed through the system. The obtained results were fitted with an exponential function that correlates characteristic time-release between samples with different pore lengths. A correlation was obtained revealing that an increase in pore length gives an increase in characteristic time-release due to the incorporation of more drugs inside the structure.
3) In separate work, two different anodization strategies i.e. sinusoidal current-density anodization and constant potential anodization combined in one electrochemical process have been successful to obtain Hy-NAA-GIF. The main aim was to obtain a modulated part on the top that consists of a PSB followed by a reservoir at the bottom showing spectrum intensity. In relation to our previous work, instead of a second PSB, the intensity of spectrum in a wavelength range far from the drug absorption region has been used. The structures were effectively loaded with the DOX using the drop-casting method followed by simultaneous measurements with the UV-VIS which allows noticing the changes in the relative height of PSB with the reflectance of the spectra intensity. Two different parameters i.e. different flow rates and pore lengths have been chosen to study the kinetics from Hy-NAA-GIF in real-time by using the same setup mentioned above. The results were then modelled with two inverted exponential decay functions which show diffusion-controlled release with two different characteristic time releases.
