Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation

Abstract

ABSTRACT. Pneumocystis carinii pneumonia (PCP) is a major opportunistic infection that affects patients with human immunodeficiency virus. Although orally administered dapsone leads to high hepatic metabolism, decreasing the therapeutic index and causing severe side effects, this drug is an effective alternative for the treatment of PCP. In this context, microencapsulation for pulmonary administration can offer an alternative to increase the bioavailability of dapsone, reducing its adverse effects. The aim of this work was to develop novel dapsone-loaded chitosan microcapsules intended for deep-lung aerosolized drug delivery. The geometric particle size (D 4,3 ) was approximately 7 μm, the calculated aerodynamic diameter (d aero ) was approximately 4.5 μm, and the mass median aerodynamic diameter from an Andersen cascade impactor was 4.7 μm. The in vitro dissolution profile showed an efficient dapsone encapsulation, demonstrating the sustained release of the drug. The in vitro deposition (measured by the Andersen cascade impactor) showed an adequate distribution and a high fine particles fraction (FPF= 50%). Scanning electron microscopy of the pulmonary tissues demonstrated an adequate deposition of these particles in the deepest part of the lung. An in vivo toxicity experiment showed the low toxicity of the drug-loaded microcapsules, indicating a protective effect of the microencapsulation process when the particles are microencapsulated. In conclusion, the pulmonary administration of the novel dapsone-loaded microcapsules could be a promising alternative for PCP treatment.

Inhalable resveratrol microparticles produced by vibrational atomization spray drying for treating pulmonary arterial hypertension

“…In addition, the fraction of powder that can be deposited in the lowers parts of the lungs (equivalent to the stages 2e7, FPF) represented by the particle size of the RSV-MP less than 5.8 mm in size (in these experimental parameters) was 46.48 ± 1.25. This FPF value is in accordance with conventional dry powder inhaler formulations [2,33]. Moreover, the MMAD of the RSV-MP obtained using the ACI was 5.22 ± 0.3 mm.…”

“…Most particles were obtained in the designed inhaled formulation, with particle sizes ranging from 1 to 5 mm for their maximum efficiency deposition in the deepest lung [11,33]. Although particles larger than 5 mm would be deposited in the throat and easily cleared, the smaller particles above 0.5 mm may not be effective due to the Brownian motion in the airstream and can be exhaled during breathing [2,24].…”

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…However, low solubility under physiological pH possesses some limitations. Due to its mucoadhesive nature [101], CS has been used as a vehicle to deliver drugs to nasal [102], ocular [103], buccal [104], and pulmonary tissues [105]. For drug delivery purposes, CS is used in the form of nano/microparticles which is synthesized by emulsion, coacervation/precipitation, ionic gelation, reverse micellar methods, etc.…”

Chemotherapeutic Evaluation of Guar Gum Coated Chitosan Nanoparticle Against Experimental Tuberculosis

“…Each plate was then assayed for the total drug deposited and particle size was determined from the cumulative mass distribution in the Anderson cascade impactor. 27 Delivered by Ingenta to: University of South In Vitro Drug Release Studies Drug release from known amount of INH and RIF loaded optimized nanoparticles (CNPs and CGNPs) was determined using the dialysis tube diffusion method at 37 ± 1 C. Both nanoparticulate dispersion (10 mL) were separately placed into the dialysis membrane (MWCO 12000-14000 Da, Himedia, India) tied at both the ends and suspended in a beaker containing 50 mL of PBS (pH 7.4). The formulations were stirred at 50 rpm and the temperature was maintained at 37 ± 1 C throughout the procedure by using shaking incubator (LSB-1005RE, Daihan labtech.…”