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<p>Cystic fibrosis (CF) is a deadly and complicated lung disease, urgently required a novel approach of treatment. Drugs such as lumacaftor (LUM), modulators of cystic fibrosis transmembrane conductance regulator (CFTR), have showed promise in partially restoring chloride transport, but their poor bioavailability and systemic toxicity highlight the need for better ways to deliver. Poly (lactic-co-glycolic acid) (PLGA) is a biocompatible and biodegradable polymer; extensively utilized in nanoparticle-based drug delivery due to its capacity to facilitate controlled and prolonged release of drugs. Chitosan (CS) is a natural, biodegradable, and mucoadhesive polymer that enhances medication stability, enables controlled release, and fosters targeted administration by increasing cellular absorption and permeability across biological membranes. This study focuses on creating CS coated LUM-loaded PLGA nanoparticles (CS-LUM-PLGA-NPs); surface camouflaged with L-132 derived cell membrane (CM) denoted as CS-LUM-PLGA-NPs@CM for enhanced targeting, retention and restoration of CFTR protein synthesis. The extensive physicochemical studies showed that they are biocompatible, spherical and found within nano range (&lt; 200&#xa0;nm). The surface coating of CS and CM on LUM-PLGA-NPs was confirmed by Transmission electron microscopy (TEM). Additionally, in vitro studies indicated the non-toxicity and enhanced cellular internalization of CS-LUM-PLGA-NPs@CM nanocarrier in L-132 cells. The inhalable nanocarrier CS-LUM-PLGA-NPs@CM significantly decreased CF-related inflammation, excessive mucus production, and fibrosis with no significant toxicity on lung tissue. The extensive in vitro and in vivo results demonstrated that this novel therapeutic approach might serve as a promising strategy for CF therapy via biomimetic and multifunctional approach.</p> Graphical Abstract <p></p>

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Hierarchical Surface-Engineered Biomimetic PLGA Nanoparticles for Targeted Pulmonary Delivery of Lumacaftor in Cystic Fibrosis

  • 期刊论文

  • 发表日期：

    2026年4月6日

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  • Santosh Kumar,
  • Md Meraj Anjum,
  • Dilip Kumar Arya,
  • Anit Kumar,
  • Shubham Kanaujiya,
  • Kunal Agam Kanaujia,
  • Prashant Pandey,
  • Mohankumar Ramar,
  • Saurabh Srivastava,
  • Parasuraman Pavadai,
  • P. S. Rajinikanth

摘要

Cystic fibrosis (CF) is a deadly and complicated lung disease, urgently required a novel approach of treatment. Drugs such as lumacaftor (LUM), modulators of cystic fibrosis transmembrane conductance regulator (CFTR), have showed promise in partially restoring chloride transport, but their poor bioavailability and systemic toxicity highlight the need for better ways to deliver. Poly (lactic-co-glycolic acid) (PLGA) is a biocompatible and biodegradable polymer; extensively utilized in nanoparticle-based drug delivery due to its capacity to facilitate controlled and prolonged release of drugs. Chitosan (CS) is a natural, biodegradable, and mucoadhesive polymer that enhances medication stability, enables controlled release, and fosters targeted administration by increasing cellular absorption and permeability across biological membranes. This study focuses on creating CS coated LUM-loaded PLGA nanoparticles (CS-LUM-PLGA-NPs); surface camouflaged with L-132 derived cell membrane (CM) denoted as CS-LUM-PLGA-NPs@CM for enhanced targeting, retention and restoration of CFTR protein synthesis. The extensive physicochemical studies showed that they are biocompatible, spherical and found within nano range (< 200 nm). The surface coating of CS and CM on LUM-PLGA-NPs was confirmed by Transmission electron microscopy (TEM). Additionally, in vitro studies indicated the non-toxicity and enhanced cellular internalization of CS-LUM-PLGA-NPs@CM nanocarrier in L-132 cells. The inhalable nanocarrier CS-LUM-PLGA-NPs@CM significantly decreased CF-related inflammation, excessive mucus production, and fibrosis with no significant toxicity on lung tissue. The extensive in vitro and in vivo results demonstrated that this novel therapeutic approach might serve as a promising strategy for CF therapy via biomimetic and multifunctional approach.

Graphical Abstract