Nanoporous Membranes for the Filtration of Proteins from Biological Fluids: Biocompatibility Tests on Cell Cultures and Suggested Applications for the Treatment of Alzheimer’s Disease

Abstract

Background: Alzheimer’s disease has a significant epidemiological and socioeconomic impact, and, unfortunately, the extensive research focused on potential curative therapies has not yet proven to be successful. However, in recent years, important steps have been made in the development and functionalization of nanoporous alumina membranes, which might be of great interest for medical use, including the treatment of neurodegenerative diseases. In this context, the aim of this article is to present the synthesis and biocompatibility testing of a special filtrating nano-membrane, which is planned to be used in an experimental device for Alzheimer’s disease treatment. Methods: Firstly, the alumina nanoporous membrane was synthesized via the two-step anodizing process in oxalic acid-based electrolytes and functionalized via the atomic layer deposition technique. Subsequently, quality control tests (spectrophotometry and potential measurements), toxicity, and biocompatibility tests (cell viability assays) were conducted. Results: The proposed alumina nanoporous membrane proved to be efficient for amyloid-beta filtration according to the permeability studies conducted for 72 h. The proposed membrane has proven to be fully compatible with the tested cell cultures. Conclusions: The proposed alumina nanoporous membrane model is safe and could be incorporated into implantable devices for further in vivo experiments and might be an efficient therapeutic approach for Alzheimer’s disease.

A Nanostructured Protein Filtration Device for Possible Use in the Treatment of Alzheimer’s Disease—Concept and Feasibility after In Vivo Tests

“…Potential measurements of the preliminary ceramic filter samples were conducted using a test cell consisting of two glass half-cells, a magnetic stirrer at the bottom of each half-cell to minimize the effect of polarization on the ceramic filter surfaces, and two Ag/AgCl reversible electrodes placed in each half-cell and connected to a digital voltmeter. This measuring technique is also presented in detail in our previous study [17]. According to the results, Aβ is in complete equilibrium on both sides after 72 h, while albumin does not cross the nanoporous ceramic filter.…”

“…According to the literature and previous experience of the authors, the optimal method for the synthesis of a highly qualitative filtrating nanoporous ceramic filter is a two-step anodizing process using oxalic acid-based electrolytes. The detailed steps for transforming aluminum disks into alumina nanoporous ceramic filters are described in another previous work by the authors [17].…”

Intrathecal Pseudodelivery of Drugs in the Therapy of Neurodegenerative Diseases: Rationale, Basis and Potential Applications

“…Nanoporous membranes are of great interest in drug delivery because they offer a secure delivery system for medications and stop bodily enzymes from breaking them down and because they can be tailored-made and fine-tuned for precise control of the rate of drug delivery or to exquisitely adjust the selective molecular permeability [ 69 , 70 ]. While a few years ago there were technical challenges for the successful application of nanoporous membranes to controlled drug delivery applications—including the need for biocompatibility, the reduction of risk of infections, and the reduction of risk of biofouling [ 71 ] most of these challenges have already been overcome and solutions are now being optimized [ 72 , 73 ]. Nanoporous membranes can be used as stand-alone DDS or assembled into complex DDS.…”

“…IT pseudodelivery is the first DDS to be endowed with nanoporous membranes acting on the CNS [ 72 , 74 , 75 ]. Devices for IT pseudodelivery of drugs look similar to intrathecal pumps as they also have a subcutaneous reservoir and an intrathecal catheter accessing the CSF.…”

“…However, they are not necessarily endowed with electromechanical pumps. The mechanism of action depends on the use of nanoporous membranes enabling selective molecular permeability [ 72 , 75 ]. On one side, the membranes do not allow crossing of drugs, but on the other side, they allow crossing of the target molecules present in the CSF.…”