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Area of Science:

  • Nanotechnology
  • Pharmacology
  • Biomedical Engineering

Background:

  • Brain cancer treatment faces challenges due to the blood-brain barrier (BBB) limiting drug efficacy.
  • Intranasal delivery offers a direct nose-to-brain pathway, bypassing the BBB for faster drug action.
  • Mucoadhesive coatings can enhance drug bioavailability and reduce systemic toxicity.

Purpose of the Study:

  • To enhance Docetaxel (DTX) delivery for brain cancer treatment using mucoadhesive poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) via intranasal administration.
  • To investigate the impact of chitosan (CS) and its derivatives (carboxymethyl chitosan - CMCS, glycol chitosan - GCS) as mucoadhesive coatings on PLGA NPs.
  • To evaluate the mucoadhesion, drug release, and pharmacokinetic profiles of the developed nanocarriers.

Main Methods:

  • Docetaxel (DTX)-loaded PLGA nanoparticles were synthesized and coated with CS, CMCS, or GCS.
  • Nanoparticles were characterized for size, surface charge, morphology, encapsulation efficiency (EE%), and loading capacity (LC%).
  • In vitro mucoadhesion and drug release studies, along with in vivo pharmacokinetic assessments in rats, were conducted.

Main Results:

  • Coated nanoparticles exhibited sizes between 209.33-339.94 nm, positive surface charge, and spherical morphology.
  • High encapsulation efficiency (>98.88%) and loading capacity (45.23-48.83%) were achieved.
  • Enhanced mucoadhesion, biphasic drug release, and significantly improved drug absorption (higher Cmax and AUC0-∞) were observed in vivo compared to controls.

Conclusions:

  • Chitosan-based coatings significantly enhance DTX absorption through the nasal mucosa, likely due to mucoadhesive and permeation-enhancing properties.
  • DTX-loaded PLGA NPs coated with CS, CMCS, and GCS show promise for targeted brain cancer therapy.
  • This intranasal delivery approach may reduce required dosage and minimize systemic side effects, warranting further efficacy and safety studies.