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We developed stable nanoparticles (SCAN) using SP-13786 (SP) excipient for improved drug delivery. SCAN enhances drug accumulation and therapeutic efficacy in fibrotic diseases.

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Area of Science:

  • Biomedical Engineering
  • Nanomedicine
  • Drug Delivery Systems

Background:

  • Nanoparticle-based drug delivery faces challenges in fabrication and accumulation.
  • Fibrotic diseases impede drug penetration and therapeutic effectiveness.
  • Fibroblast Activation Protein (FAP) is a target in fibrotic conditions.

Purpose of the Study:

  • To introduce SP-13786 (SP) as a universal excipient for creating stable nanoparticles (SCAN) with hydrophobic drugs.
  • To investigate the assembly mechanism of SCAN using simulations and explainable machine learning (XML).
  • To evaluate the therapeutic potential of SCAN in fibrotic disease models.

Main Methods:

  • Co-precipitation of SP-13786 with hydrophobic drugs to form SCAN.
  • Compound screening (861 candidates) to identify SP as an effective excipient.
  • Computational simulations and explainable machine learning (XML) for analyzing SCAN assembly.
  • In vitro and in vivo biological assessments in FAP-positive cells and disease models.

Main Results:

  • SP significantly enhanced colloidal stability and drug loading for diverse hydrophobic drugs.
  • SCAN assembly is governed by balanced aromaticity, rigidity, and nitrogen-mediated interactions.
  • SCAN improved drug delivery and efficacy in FAP-positive cells.
  • SCAN attenuated fibrosis-induced drug penetration barriers, increasing drug accumulation in fibrotic tissues.
  • Enhanced bioavailability of SCAN correlated with superior therapeutic outcomes in progressive fibrosis models.

Conclusions:

  • SP-13786 is a versatile excipient for developing stable nanoparticles (SCAN) via facile co-precipitation.
  • XML provides mechanistic insights into SCAN assembly, enabling rational nanomedicine design.
  • SCAN represents a promising nanotherapeutic platform for treating diseases with pathological fibrosis and impaired drug delivery.