Kannavou Maria, Karali Kanelina, Katsila Theodora, Siapi Eleni, Marazioti Antonia, Klepetsanis Pavlos, Calogeropoulou Theodora, Charalampopoulos Ioannis, Antimisiaris Sophia G
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, 26510 Rio, Greece.
Foundation for Research and Technology Hellas, Institute of Chemical Engineering Sciences, FORTH/ICE-HT, 26504 Rio, Greece.
Pharmaceutics. 2023 Jan 27;15(2):419. doi: 10.3390/pharmaceutics15020419.
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% / Capmul-MCM and 0.3% / 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.
鼻内给药为直接鼻脑递送提供了一种有前景的替代方法。在此，我们制备了两种壳聚糖（CHT）包被（和未包被）的BNN27（一种合成的C-17-螺-脱氢表雄酮类似物）纳米制剂，即脂质体（LIPs）和纳米乳剂（NEs），并比较了它们的性质和脑内分布（体外和体内）。脂质体通过薄膜水化法制备，并通过逐滴添加的方式用壳聚糖包被。载有BNN27的纳米乳剂（BNEs）通过自发乳化法制备，并针对稳定性和粘膜粘附特性进行了优化。通过粘蛋白粘附评估粘膜粘附特性。带负电荷的壳聚糖包被脂质体（含0.1%壳聚糖/脂质）表现出最高的包被效率和粘膜粘附性。含有10% / Capmul-MCM和0.3% / 壳聚糖的BNEs表现出最佳性能。与脂质体相比，纳米乳剂在体外跨血脑屏障转运与脂质体或纳米乳剂相关的罗丹明脂质的能力显著更高，并且壳聚糖包被对转运有负面影响。然而，与壳聚糖包被的脂质体相比，壳聚糖包被的BNEs在鼻内给药后在体内脑内分布更高且更快。对于BNEs和脂质体，壳聚糖包被均导致BNN27在体内脑内分布增加。目前的结果证明，与壳聚糖包被的脂质体相比，由相容性鼻内给药成分组成的壳聚糖包被的纳米乳剂成功地将更多的BNN27更快地递送至脑内。
