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<p>The treatment of central nervous system (CNS) disorders remains a significant challenge due to the restrictive nature of the blood–brain barrier (BBB). Conventional nanocarriers (NCs) are associated with several drawbacks, including inadequate targeting, low drug encapsulation, and poor drug penetration. Target-specific ligands can be used to modify the surface of NCs, enhancing their transport across the BBB and overcoming the delivery limitations of conventional NCs. Among these, lactoferrin (Lf), an iron-binding glycoprotein of the transferrin (Tf) family, has gained considerable attention as a targeting ligand due to its biodegradable nature, ability to bind with transferrin receptors and lactoferrin receptors (LfRs), which are overexpressed on the BBB and various pathological tissues in NDs. Lf facilitates receptor-mediated transcytosis (RMTs), promoting efficient drug transport into the brain, while also exhibiting antioxidant and neuroprotective effects. This review explores the potential of Lf-coated NCs in CNS drug delivery, focusing on neurodegenerative disorders (NDs). Various Lf-coated NCs, including lipid-based nanoparticles (NPs), inorganic NCs, dendrimers, biodegradable polymers, and nanoemulsions (NEs), are examined regarding their design and functionalization strategies. As a result, the first section of the article covers the physicochemical characteristics and significance of the targeting ligand (Lf), as well as an overview of several NCs and their functionalization through Lf. The second part discusses recent examples of Lf-coated NCs&#xa0;and their applications in treating a variety of disorders, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and others. Additionally, recent advancements in Lf-based nanomedicine are discussed, highlighting its role as both an active therapeutic and a drug NCs. This review provides critical insights into the evolving landscape of Lf-coated NCs, underscoring their potential to revolutionize CNS drug delivery and contribute to more effective therapeutic interventions for NDs. Finally, obstacles to clinical translation were explored, along with and future perspectives.</p> Graphical abstract <p></p>

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Navigating into the paradigm of lactoferrin surface modified nanocarriers in the management of central nervous system disorders

  • 期刊论文

  • 发表日期：

    2025年6月21日

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  • Aneri Desai,
  • Pranav Shah,
  • Sanyog Jain

摘要

The treatment of central nervous system (CNS) disorders remains a significant challenge due to the restrictive nature of the blood–brain barrier (BBB). Conventional nanocarriers (NCs) are associated with several drawbacks, including inadequate targeting, low drug encapsulation, and poor drug penetration. Target-specific ligands can be used to modify the surface of NCs, enhancing their transport across the BBB and overcoming the delivery limitations of conventional NCs. Among these, lactoferrin (Lf), an iron-binding glycoprotein of the transferrin (Tf) family, has gained considerable attention as a targeting ligand due to its biodegradable nature, ability to bind with transferrin receptors and lactoferrin receptors (LfRs), which are overexpressed on the BBB and various pathological tissues in NDs. Lf facilitates receptor-mediated transcytosis (RMTs), promoting efficient drug transport into the brain, while also exhibiting antioxidant and neuroprotective effects. This review explores the potential of Lf-coated NCs in CNS drug delivery, focusing on neurodegenerative disorders (NDs). Various Lf-coated NCs, including lipid-based nanoparticles (NPs), inorganic NCs, dendrimers, biodegradable polymers, and nanoemulsions (NEs), are examined regarding their design and functionalization strategies. As a result, the first section of the article covers the physicochemical characteristics and significance of the targeting ligand (Lf), as well as an overview of several NCs and their functionalization through Lf. The second part discusses recent examples of Lf-coated NCs and their applications in treating a variety of disorders, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and others. Additionally, recent advancements in Lf-based nanomedicine are discussed, highlighting its role as both an active therapeutic and a drug NCs. This review provides critical insights into the evolving landscape of Lf-coated NCs, underscoring their potential to revolutionize CNS drug delivery and contribute to more effective therapeutic interventions for NDs. Finally, obstacles to clinical translation were explored, along with and future perspectives.

Graphical abstract