Development and Comparative In Vitro and In Vivo Study of BNN27 Mucoadhesive Liposomes and Nanoemulsions for Nose-to-Brain Delivery

Author:

Kannavou Maria12,Karali Kanelina34,Katsila Theodora5ORCID,Siapi Eleni5,Marazioti Antonia12,Klepetsanis Pavlos12,Calogeropoulou Theodora5ORCID,Charalampopoulos Ioannis34ORCID,Antimisiaris Sophia G.12ORCID

Affiliation:

1. Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, 26510 Rio, Greece

2. Foundation for Research and Technology Hellas, Institute of Chemical Engineering Sciences, FORTH/ICE-HT, 26504 Rio, Greece

3. Department of Pharmacology, Medical School, University of Crete, 71003 Heraklion, Greece

4. Institute of Molecular Biology & Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), 70013 Heraklion, Greece

5. Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece

Abstract

Intranasal administration offers an alternative and promising approach for direct nose-to-brain delivery. Herein, we developed two chitosan (CHT)-coated (and uncoated) nanoformulations of BNN27 (a synthetic C-17-spiro-dehydroepiandrosterone analogue), liposomes (LIPs), and nanoemulsions (NEs), and compared their properties and brain disposition (in vitro and in vivo). LIPs were formulated by thin film hydration and coated with CHT by dropwise addition. BNN27-loaded NEs (BNEs) were developed by spontaneous emulsification and optimized for stability and mucoadhesive properties. Mucoadhesive properties were evaluated by mucin adherence. Negatively charged CHT-coated LIPs (with 0.1% CHT/lipid) demonstrated the highest coating efficiency and mucoadhesion. BNEs containing 10% w/w Capmul-MCM and 0.3% w/w CHT demonstrated the optimal properties. Transport of LIP or NE-associated rhodamine-lipid across the blood–brain barrier (in vitro) was significantly higher for NEs compared to LIPs, and the CHT coating demonstrated a negative effect on transport. However, the CHT-coated BNEs demonstrated higher and faster in vivo brain disposition following intranasal administration compared to CHT-LIPs. For both BNEs and LIPs, CHT-coating resulted in the increased (in vivo) brain disposition of BNN27. Current results prove that CHT-coated NEs consisting of compatible nasal administration ingredients succeeded in to delivering more BNN27 to the brain (and faster) compared to the CHT-coated LIPs.

Publisher

MDPI AG

Subject

Pharmaceutical Science

Cited by 5 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. In-depth Mechanism, Challenges, and Opportunities of Delivering Therapeutics in Brain Using Intranasal Route;AAPS PharmSciTech;2024-05-06

2. Research progress in brain-targeted nasal drug delivery;Frontiers in Aging Neuroscience;2024-01-17

3. Liposomes for drug delivery to the brain;Liposomes in Drug Delivery;2024

4. Chitosan Biomaterials: Advances and Challenges;International Journal of Molecular Sciences;2023-11-10

5. Preparation of mucoadhesive methacrylated chitosan nanoparticles for delivery of ciprofloxacin;International Journal of Biological Macromolecules;2023-07

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