Drug Delivery Systems as a Strategy to Improve the Efficacy of FDA-Approved Alzheimer’s Drugs
Open accessAbstract
Alzheimer’s disease (AD) is the most common form of dementia, with a high impact worldwide, accounting for more than 46 million cases. The continuous increase of AD demands the fast development of preventive and curative therapeutic strategies that are truly effective. The drugs approved for AD treatment are classified into acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The therapeutic effectiveness of those drugs is hindered by their restricted access to the brain due to the blood–brain barrier, low bioavailability, and poor pharmacokinetic properties. In addition, the drugs are reported to have undesirable side effects. Several drug delivery systems (DDSs) have been widely exploited to address these issues. DDSs serve as drug carriers, combining the ability to deliver drugs locally and in a targeted manner with the ability to release them in a controlled and sustained manner. As a result, the pharmacological therapeutic effectiveness is raised, while the unwanted side effects induced by the unspecific distribution decrease. This article reviews the recently developed DDSs to increase the efficacy of Food and Drug Administration-approved AD drugs.
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Nanotechnology-based drug delivery systems using nanoparticles offer high stability, loading capacity, bioavailability, protection against enzymatic degradation, and sustained and localized release.
“These systems offer an enhanced value due to high stability, loading capacity, and bioavailability, protection against enzymatic degradation, and creation of a sustained and localized release.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [7]
The Introduction and §4.1 (page unavailable) support improved bioavailability, protection against enzymatic degradation, and sustained, localized release. Section 4.4 supports drug loading, but the paper does not establish that nanoparticle systems generally have high stability or high loading capacity; it says nanoparticle stability depends on the materials used and attributes increased loading capability to nanoparticle-loaded hydrogels. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDifferent engineered nanoparticles can penetrate the blood-brain barrier and serve as efficient drug delivery systems into the brain.
“Different types of engineered nanoparticles (NPs) have been demonstrated to be able to penetrate this barrier and serve as efficient drug delivery systems (DDS) into the brain, making them a promising solution for future therapeutic development.”
Nanoparticles can overcome free drug limitations such as lack of selectivity and reduce the risk of adverse secondary effects by decreasing the administered drug concentration.
“Additionally, they can overcome the free drug’s limitations, like a lack of selectivity, and reduce the risk of adverse secondary effects by decreasing the drug’s administered concentration [7,8].”
Nanoparticles are proposed as an effective alternative to cross the blood-brain barrier because their surface can be engineered to circumvent this biological barrier.
“In this way, they are proposed as an effective alternative to cross the BBB once their surface can be easily engineered to circumvent this biological barrier.”
FDA and EMA-approved drugs to treat AD have limitations (e.g., side effects, ineffective passage across the BBB, poor bioavailability, pharmacokinetics, and pharmacodynamics) that have been shown to be overcome by their employment in NPs.
“Even the FDA and EMA-approved drugs to treat AD have been reported to manifest limitations (e.g., side effects, ineffective passage across the BBB, poor bioavailability, pharmacokinetics, and pharmacodynamics) that have been shown to be overcome by their employment in NPs [7].”
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Small Molecules for Drug Development of Alzheimer’s Disease
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Kumar, V., Kakoty, V., & Wadhwa, P. K. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05901-0
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Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives
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- Authors
- Nunes, D., Loureiro, J. A., & Pereira, M. C.
- Affiliations
- Universidade do Porto (PT)
- LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
- Corresponding author
- Loureiro, Joana A.
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2022-10-26
- Volume
- 14
- Issue
- 11
- Pages
- 2296
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC9694621
- OpenAlex
- W4307548872
- Cited by
- 68
- References
- 130
- Citations by year
- 2026: 20 · 2025: 24 · 2024: 13 · 2023: 10 · 2022: 1
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- FCT/MCTES (PIDDAC) (LA/P/0045/2020, UIDP/00511/2020, NORTE-01-0145-FEDER-000054, UI/BD/150946/2021, CEECINST/00049/2018)
- European Regional Development Fund (ERDF) (LA/P/0045/2020, UIDP/00511/2020, NORTE-01-0145-FEDER-000054, UI/BD/150946/2021, CEECINST/00049/2018)
- FCT (LA/P/0045/2020, UIDP/00511/2020, NORTE-01-0145-FEDER-000054, UI/BD/150946/2021, CEECINST/00049/2018)
- Scientific Employment Stimulus—Institutional Call (LA/P/0045/2020, UIDP/00511/2020, NORTE-01-0145-FEDER-000054, UI/BD/150946/2021, CEECINST/00049/2018)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, drug delivery systems, acetylcholinesterase inhibitors, NMDA receptor antagonists, blood-brain barrier, bioavailability, pharmacokinetics, targeted drug delivery, controlled drug release, FDA-approved drugs, adverse drug reactions
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