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Intratracheal Administration of Dry Powder Formulation in Mice

Intratracheal Administration of Dry Powder Formulation in Mice

Published on: July 25, 2020

Inhalable DNase I microparticles engineered with biologically active excipients.

Rihab Osman¹, Khuloud T Al Jamal, Pei-Lee Kan

¹UCL-School of Pharmacy, London University, 29-39 Brunswick Square, London WC1N1AX, UK; Faculty of Pharmacy, Ain Shams University, P.O. Box:11566, Cairo, Egypt.

Pulmonary Pharmacology & Therapeutics

|August 13, 2013

Summary

Surface modifying microparticles with dextran or polyanions enhances DNase I delivery for cystic fibrosis mucus. This improves enzyme stability, lung deposition, and mucolytic activity, offering a promising therapeutic approach.

Keywords:

Cystic fibrosis DNase I Dextran Leucine Polyanions Pulmonary

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Area of Science:

Biomedical Engineering
Drug Delivery
Respiratory Medicine

Background:

Cystic fibrosis (CF) is characterized by highly viscous mucus, impeding effective particulate therapeutic delivery to the lungs.
DNase I is a crucial enzyme for breaking down DNA in CF mucus, but its delivery and stability are challenging.

Purpose of the Study:

To develop and evaluate surface-modified microparticles (MP) loaded with DNase I for improved cystic fibrosis therapy.
To investigate the impact of various excipients on particle characteristics, enzyme stability, aerosolization, and biological activity.

Main Methods:

Controlled-release microparticles (MP) were fabricated using co-spray drying of DNase I with poly-lactic-co-glycolic acid (PLGA) and 1,2-dipalmitoyl-Sn-phosphatidyl choline (DPPC).
Various hydrophilic excipients (dextran, ovalbumin, chitosan hydrochloride, lactose, PVP) were used for surface modification.
Particle properties (morphology, size, zeta potential), enzyme encapsulation efficiency, biological activity, release kinetics, aerosolization performance, and phagocytosis were assessed.
Mucolytic activity in artificial CF mucus and biocompatibility with lung epithelial cells were evaluated.

Main Results:

Over 80% of DNase I activity was retained post-preparation, with surface modifiers significantly enhancing encapsulation efficiency.
Excipients like dextran and chitosan hydrochloride improved the respirable fraction of the microparticles.
Dextran and polyanions demonstrated enhanced DNase I efficacy in reducing CF mucus viscosity.
1,2-dipalmitoyl-Sn-phosphatidyl choline (DPPC) reduced particle phagocytosis, and the microparticles showed biocompatibility with lung cells.

Conclusions:

Surface modification of PLGA-MP with dextran or polyanions yields DNase I-loaded particles with high inhalation indices and enhanced mucolytic activity for CF sputum.
These optimized microparticles offer a promising strategy for improved therapeutic delivery in cystic fibrosis patients.