Development of Thermosensitive Mucoadhesive Gel Based Encapsulated Lipid Microspheres as Nose-to-Brain Rivastigmine Delivery System

IF 3.7 2区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Langmuir Pub Date : 2024-12-23 DOI:10.1021/acs.langmuir.4c03530

Nurafni Annisa Achmad, Rachmatya W. Tuna, Irfan Kurniawan, Khairiyah, Muhammad Bisfain Asaf, Latifah Rahman, Marianti A. Manggau, Aliyah, Juan Dominguez-Robles, Muhammad Aswad, Andi Dian Permana

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引用次数: 0

Abstract

Alzheimer’s disease (ALZ) is a neurodegenerative disease that damages neuronal cells and causes decline in cognitive abilities. Administration of cholinesterase inhibitor compounds is the primary choice in the treatment of ALZ, one of which is rivastigmine (RVT). Several routes of administration of RVT are available, such as oral and transdermal. However, in the oral route, RVT has low bioavailability, undergoes first-pass metabolism, and the presence of the blood-brain barrier (BBB) reduces the therapeutic concentration of RVT. The transdermal route is nonselective target in the brain. This study aims to combine thermosensitive mucoadhesive gel (TG) and lipid microspheres (LM) as a drug delivery system to improve the efficacy of RVT. Combining these will prevent systemic side effects of RVT and increase drug concentration in the brain. LM was formulated with varying concentrations of Compritol polymer. The results of LM evaluation showed the values of particle size, PDI, and %EE and %DL were 8.519 μm, 0.018 ± 0.004, 72.54%, and 76.43%, respectively. The TG formulation can provide a liquid form at room temperature (25 °C) and a gel at nasal temperature (35 °C). Hemolytic and HET-CAM tests confirmed TG RVT LM’s safety for use. Ex vivo studies showed controlled and sustained release of TG RVT LM, and in vivo studies showed TG RVT LM a higher pharmacokinetic profile in the brain than oral formulations and injections. The C_max was found to be 7.05 ± 0.55 μg/cm³, T_max was 24 h, and AUC_0–24, which is related to the effectiveness of brain targeting, was 225.73 μg/cm³. In conclusion, this study shows the successful development of TG RVT LM, as evidenced by improved drug delivery to the brain, which is characterized by higher concentrations of RVT in the brain compared with oral and injectable RVT, this delivery system shows potential as a future treatment for Alzheimer’s disease.

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来源期刊

Langmuir 化学-材料科学：综合

CiteScore

6.50

自引率

10.30%

发文量

1464

审稿时长

2.1 months

期刊介绍： Langmuir is an interdisciplinary journal publishing articles in the following subject categories: Colloids: surfactants and self-assembly, dispersions, emulsions, foams Interfaces: adsorption, reactions, films, forces Biological Interfaces: biocolloids, biomolecular and biomimetic materials Materials: nano- and mesostructured materials, polymers, gels, liquid crystals Electrochemistry: interfacial charge transfer, charge transport, electrocatalysis, electrokinetic phenomena, bioelectrochemistry Devices and Applications: sensors, fluidics, patterning, catalysis, photonic crystals However, when high-impact, original work is submitted that does not fit within the above categories, decisions to accept or decline such papers will be based on one criteria: What Would Irving Do? Langmuir ranks #2 in citations out of 136 journals in the category of Physical Chemistry with 113,157 total citations. The journal received an Impact Factor of 4.384*. This journal is also indexed in the categories of Materials Science (ranked #1) and Multidisciplinary Chemistry (ranked #5).