FORMULATION, OPTIMIZATION, AND CHARACTERIZATION OF BIOCOMPATIBLE INHALABLE D-CYCLOSERINE-LOADED ALGINATE-CHITOSAN NANOPARTICLES FOR PULMONARY DRUG DELIVERY
Objective: To prepare Nanoparticulate dosage form having improved drug bioavailability and reduced dosing frequency of antitubercular drugs
which will helps in improving patient compliance in the treatment of multi-drug resistant tuberculosis (MDR-TB).
Methods: Ionotropic gelation method was used to prepare D-cycloserine (D-CS)-loaded alginate-chitosan nanoparticles, and the particles are
characterized by their particle size and morphology using particle size analyzer and scanning electron microscopy (SEM). X-ray diffraction (XRD),
differential scanning calorimetry (DSC), and Fourier-transformed infrared (FTIR) studies were used to determine drug-polymer interactions and drug
entrapment. Entrapment efficiency, drug loading (DL), particle size, and zeta potential of nanoparticles were also studied. The 2
factorial designs of
experiments by Design-Expert
V9 were used to optimize the particle size and entrapment efficiency of nanoparticles.
Results: The optimized batch had shown the entrapment efficiency of 98.10Â±0.24% and DL of 69.32Â±0.44% with particle size and zeta potential
as 344Â±5 nm and âˆ’42Â±11.40 mV, respectively. DSC, FTIR, and XRD studies confirmed the drug entrapment within nanoparticle matrix. SEM results
showed spherical-shaped particles. Sustained release of drug from the nanoparticles was observed for 24 hrs period. Respirable fraction up to
52.37Â±0.7% demonstrates the formulation suitability for deep lung delivery. Lung inflammatory study showed a less inflammatory response.
Conclusion: Ionotropic gelation method can be used to prepare biocompatible particles with a high entrapment efficiency, DL, optimum particle size,
and controlled release characteristics, which can serve as a convenient delivery system for D-CS and could be a potential alternative to the existing
conventional therapy in MDR-TB.
Keywords: Nanoparticles, Alginate, Chitosan, Inhalation, Sustained release, Tuberculosis.
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