Formulation considerations in enhancing olfactory mucosal deposition for nose-to-brain drug delivery.

IF 6.9 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Drug Delivery and Translational Research Pub Date : 2026-08-01 Epub Date: 2026-03-21 DOI:10.1007/s13346-026-02097-7

Anisha A DSouza, Maayan Kahan, Alicia Yang, Smrithi Padmakumar, Benjamin S Bleier, Mansoor M Amiji

{"title":"Formulation considerations in enhancing olfactory mucosal deposition for nose-to-brain drug delivery.","authors":"Anisha A DSouza, Maayan Kahan, Alicia Yang, Smrithi Padmakumar, Benjamin S Bleier, Mansoor M Amiji","doi":"10.1007/s13346-026-02097-7","DOIUrl":null,"url":null,"abstract":"<p><p>Nose-to-brain (N2B) drug delivery offers a promising alternative to circumvent the blood-brain barrier and deliver therapeutic agents directly to the central nervous system. Among the intranasal pathways, targeting the olfactory mucosa is particularly attractive due to its direct anatomical and functional connection to the brain. However, effective deposition and retention of drug-loaded formulations in the olfactory region remain significant challenges, owing to complex nasal anatomy, mucociliary clearance, and limited surface area. This review critically examines the physiological and anatomical barriers to olfactory targeting and highlights recent advances in nanoparticle-based strategies designed to enhance mucosal deposition and transport. Various formulation approaches-including mucoadhesive polymers, surface-functionalized nanocarriers, and stimuli-responsive systems-are discussed alongside innovative delivery devices and administration techniques tailored for olfactory mucosal delivery. In vitro, ex vivo, and in vivo models used to evaluate these strategies are reviewed, as are safety, regulatory, and translational considerations. Finally, the review explores emerging technologies such as patient-specific delivery platforms and smart nanoparticles, offering a forward-looking perspective on the future of N2B therapeutics for neurological disorders.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2552-2577"},"PeriodicalIF":6.9000,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346265/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Delivery and Translational Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13346-026-02097-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/3/21 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Nose-to-brain (N2B) drug delivery offers a promising alternative to circumvent the blood-brain barrier and deliver therapeutic agents directly to the central nervous system. Among the intranasal pathways, targeting the olfactory mucosa is particularly attractive due to its direct anatomical and functional connection to the brain. However, effective deposition and retention of drug-loaded formulations in the olfactory region remain significant challenges, owing to complex nasal anatomy, mucociliary clearance, and limited surface area. This review critically examines the physiological and anatomical barriers to olfactory targeting and highlights recent advances in nanoparticle-based strategies designed to enhance mucosal deposition and transport. Various formulation approaches-including mucoadhesive polymers, surface-functionalized nanocarriers, and stimuli-responsive systems-are discussed alongside innovative delivery devices and administration techniques tailored for olfactory mucosal delivery. In vitro, ex vivo, and in vivo models used to evaluate these strategies are reviewed, as are safety, regulatory, and translational considerations. Finally, the review explores emerging technologies such as patient-specific delivery platforms and smart nanoparticles, offering a forward-looking perspective on the future of N2B therapeutics for neurological disorders.

查看原文本刊更多论文

加强鼻-脑给药嗅觉粘膜沉积的配方考虑。

鼻到脑（N2B）给药提供了一种很有前途的替代方案，可以绕过血脑屏障，将治疗药物直接输送到中枢神经系统。在鼻内通路中，以嗅觉粘膜为靶点特别有吸引力，因为它与大脑有直接的解剖和功能联系。然而，由于复杂的鼻腔解剖结构、纤毛粘膜清除和有限的表面积，在嗅觉区域有效沉积和保留药物负载制剂仍然是一个重大挑战。这篇综述严格审查了嗅觉靶向的生理和解剖学障碍，并强调了基于纳米颗粒的策略的最新进展，这些策略旨在增强粘膜沉积和运输。各种配方方法，包括黏附聚合物、表面功能化纳米载体和刺激反应系统，以及为嗅觉粘膜输送量身定制的创新输送装置和给药技术。本文回顾了用于评估这些策略的体外、离体和体内模型，以及安全性、监管和翻译方面的考虑。最后，综述探讨了新兴技术，如患者特异性递送平台和智能纳米颗粒，为神经系统疾病N2B治疗的未来提供了前瞻性的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.