Hydroxypropyl-β-Cyclodextrin Formulated in Nasal Chitosan Microspheres as Candidate Therapeutic Agent in Alzheimer’s Disease
Abstract
Hydroxypropyl-β-cyclodextrin (HP-CD) is a hydroxyalkyl derivative of native β-cyclodextrin, cyclic oligosaccharide able to form inclusion complexes with many drugs and biomolecules [1]. Cyclodextrins have a possible neuroprotective effect due to their capability to extract and deplete cholesterol from cell membranes [1]. HP-CD is classified as an excipient (cyclodextrins are in fact widely used to improve solubility of poorly water soluble drugs) and it is not been FDA-approved as therapeutic agent. However HP-CD received the "orphan drug designation" in the United States and Europe because it is employed in individual compassionate use for patients suffering from Niemann-Pick type C. This is a fatal neurological disease characterized by an abnormal storage of cholesterol within the cells and in particular nervous cells causing neurodegeneration [2]. Elevated cholesterol levels produce also the accumulation of beta-amyloid (Aβ) in cellular systems and several animal models of Alzheimer's disease (AD) [3]. AD is a chronic neurodegenerative disease which affects nearly 44 million people worldwide and the global cost of Alzheimer's disease and dementia is estimated to be $605 billion [4]. Cholesterol depletion, disruption or inhibition of Aβ aggregation are possible therapeutic approaches of AD.
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Different kinds of nanocarriers used to prepare nasal formulations able to target the brain include polymer-based and lipid-based nanoparticles.
“According to the present literature, different kinds of nanocarriers are used to prepare nasal formulations able to target the brain, constituted by polymer-based and lipid-based nanoparticles [21,22,23].”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [23]
Cyclodextrins can be used for the preparation of formulations able to cross the blood-brain barrier, administered through nasal or oral/parenteral routes.
“For instance, it is known that cyclodextrins can be used for the preparation of formulations able to cross the BBB, administered through nasal or oral/parenteral routes [16,23,80,81].”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [23]
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Chitosan-Based (Nano)Materials for Novel Biomedical Applications
Kravanja, G., Primožič, M., Knez, Ž., & Leitgeb, M. (2019) · Molecules · doi:10.3390/molecules24101960 · Cited by 416 · see citing works
“Nasal chitosan microspheres Hydroxypropyl–cyclodextrin Alzheimer’s disease Nasal route [140]”
BackgroundNanoemulsions for “Nose-to-Brain” Drug Delivery
Bonferoni, M. C., Rossi, S., Sandri, G., Ferrari, F., Gavini, E., Rassu, G., & Giunchedi, P. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11020084 · Cited by 269 · see citing works
“For instance, it is known that cyclodextrins can be used for the preparation of formulations able to cross the BBB, administered through nasal or oral/parenteral routes [16,23,80,81].”
BackgroundSelf-citationProgress in nasal drug delivery systems
Laffleur, F., & Bauer, B. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120994 · Cited by 189 · see citing works
Preparation and applications of chitosan and cellulose composite materials
Ambaye, T. G., Vaccari, M., Prasad, S., van Hullebusch, E. D., & Rtimi, S. (2021) · Journal of Environmental Management · doi:10.1016/j.jenvman.2021.113850 · Cited by 162 · see citing works
Versatile Nasal Application of Cyclodextrins: Excipients and/or Actives?
Rassu, G., Sorrenti, M., Catenacci, L., Pavan, B., Ferraro, L., Gavini, E., Bonferoni, M. C., Giunchedi, P., & Dalpiaz, A. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13081180 · Cited by 51 · see citing works
“The results obtained demonstrated that HP-β-CD can reach the brain after nasal administration, particularly the hippocampus, where it provides a protective action against Aβ-induced excitotoxicity [77,92].”
BackgroundSelf-citationRassu, G., Fancello, S., Roldo, M., et al. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12070658 · Cited by 40 · see citing works
“Moreover, HP is able to provide protection against neurotoxicity induced by β-amyloid, and therefore useful in the treatment of Alzheimer’s disease [8-10].”
Self-citationMatías‐Guiu, J., Matías‐Guiu, J. A., Montero‐Escribano, P., Barcia, J. A., Canales-Aguirre, A. A., Mateos‐Díaz, J. C., & Gómez‐Pinedo, U. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00638 · Cited by 12 · see citing works
Gómez‐Pinedo, U., Matías‐Guiu, J. A., Benito‐Martín, M. S., Moreno‐Jiménez, L., Sanclemente-Alamán, I., Selma-Calvo, B., Pérez-Suarez, S., Sancho-Bielsa, F. J., Canales-Aguirre, A. A., Mateos‐Díaz, J. C., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910738 · Cited by 9 · see citing works
- Authors
- Rassu, G., Gavini, E., Carta, A., Obinu, A., Porcu, E. P., & Giunchedi, P.
- Affiliations
- University of Sassari (IT)
- University of Pavia (IT)
- Corresponding author
- Giunchedi, Paolo
- Venue
- Current Drug Delivery
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2018-06-27
- Volume
- 15
- Issue
- 6
- Pages
- 746-748
- ISSN
- 1567-2018 (ISSN-L)
- OpenAlex
- W2765778222
- Cited by
- 8
- References
- 0
- Citations by year
- 2021: 4 · 2020: 2 · 2019: 2
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Drug Delivery (publishedVersion)
- PubMed (publishedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- hydroxypropyl-β-cyclodextrin, chitosan microspheres, intranasal drug delivery, Alzheimer's disease, drug formulation, therapeutic agents
- MeSH terms
- 2-Hydroxypropyl-beta-cyclodextrin, Administration, Intranasal, Alzheimer Disease, Drug Carriers, Drug Compounding, Humans, Microspheres, Orphan Drug Production, Neuroprotective Agents, Chitosan
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