Fabrication and application of dimyristoyl phosphatidylcholine biomaterial-based nanocochleates dry powder inhaler for controlled release resveratrol delivery

Abstract Background Resveratrol, a bioactive phytoconstituent, is used to treat chronic respiratory diseases. However, its clinical application was hampered due to its poor bioavailability. In the present study, controlled release of resveratrol loaded nanocochleate-based dry powder inhaler was investigated to improve its biopharmaceutical properties for pulmonary drug delivery. The in vivo toxicity study was performed in the healthy male albino Wistar rats by intracheal administration. Results Resveratrol loaded nanocochleate-based dry powder inhaler was prepared by lyophilizing the resveratrol loaded dimyristoylphosphatidylcholine sodium and calcium ion-based nanocochleates using mannitol as cryoprotectant. Resveratrol loaded nanocochleates showed a particle size and encapsulation efficiency of 329.18 ± 9.43 nm and 76.35 ± 3.65%, respectively. Resveratrol loaded nanocochleate-based dry powder exhibited a particle size of 102.21 ± 9.83 μm and satisfactory flowability with initial burst release followed by extended release up to 96 h. The in vitro drug deposition pattern using multistage cascade impactor showed 1.28-fold improvement in fine particle dose, and the in vivo toxicity potential by histopathological study in albino rats revealed safety of formulation. Conclusions Resveratrol loaded nanocochleate-based dry powder inhaler could serve as an efficient delivery system for the treatment of chronic respiratory diseases. Graphical abstract

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Development of Dry Powder Inhaler Containing Prothionamide-PLGA Nanoparticles Optimized Through Statistical Design: In-vivo Study

The Open Nanomedicine Journal ◽

10.2174/1875933501704010030 ◽

2017 ◽

Vol 4 (1) ◽

pp. 30-40 ◽

Cited By ~ 2

Author(s):

Sujit K. Debnath ◽

Saisivam Srinivasan ◽

Monalisha Debnath

Keyword(s):

Particle Size ◽

Drug Release ◽

Dry Powder Inhaler ◽

Burst Release ◽

Dry Powder ◽

Box Behnken Design ◽

Pulmonary Administration ◽

Aerodynamic Particle Size

Objective:The objective of the present work was to formulate Prothionamide (PTH) nanoparticles using Poly lactic co-glycolic acid (PLGA), optimized by Box-Behnken Design and further modification to dry powder inhaler followed byin-vivostudy.Methods:Poly-lactic co-gycolic acid (PLGA), a biodegradable polymer was used to coat Prothionamide by solvent evaporation technique. Formulation was optimized using Box-Behnken Design. Response surface curve and desirability factors helped in the selection of optimum formulation of PTH nanoparticles. Dry powder inhaler was prepared by adding inhalable grade lactose to optimize PTH nanoparticles. Mass median aerodynamic diameter (MMAD) was carried out using Andersen Cascade Impactor (ACI) to demonstrate its suitability in the pulmonary administration.In-vitrodrug release of dry powder inhaler was carried out in simulated lungs fluid. Correlationin-vitrotoin-vivowas established after performing animal experiment.Results:FTIR study reveals no chemical interaction between PTH, lactose and PLGA as the principle peaks was retained with same intensity in the physical mixture. Scanning electron microscope showed the spherical shape and aerodynamic particle size was found to be 1.69µm. Drug release study showed initial burst release followed by zero order release.In-vivomodel confirmed the presence of PTH after 24h. Aerodynamic particle size and the release profile revealed the suitability of PTH loaded nanoparticles containing dry powder inhaler for the pulmonary administration.Conclusion:Prepared DPI containing PTH nanoparticles can improve in the management of tuberculosis by increasing PTH residency in the lungs tissue for prolong period of time.

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Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In Vitro–In Silico Approach

Pharmaceutics ◽

10.3390/pharmaceutics13030297 ◽

2021 ◽

Vol 13 (3) ◽

pp. 297

Author(s):

Joana T. Pinto ◽

Inês Cachola ◽

João F. Pinto ◽

Amrit Paudel

Keyword(s):

Particle Size ◽

In Silico ◽

Low Dose ◽

Drug Product ◽

Dry Powder Inhaler ◽

Dry Powder ◽

Bulk Properties ◽

Pbpk Models

The use of physiologically based pharmacokinetic (PBPK) models to support drug product development has become increasingly popular. The in vitro characterization of the materials of the formulation provides valuable descriptors for the in silico prediction of the drug’s pharmacokinetic profile. Thus, the application of an in vitro–in silico framework can be decisive towards the prediction of the in vivo performance of a new medicine. By applying such an approach, this work aimed to derive mechanistic based insights into the potential impact of carrier particles and powder bulk properties on the in vivo performance of a lactose-based dry powder inhaler (DPI). For this, a PBPK model was developed using salbutamol sulphate (SS) as a model drug and the in vitro performance of its low-dose blends (2% w/w) with different types of lactose particles was investigated using different DPI types (capsule versus reservoir) at distinct airflows. Likewise, the influence of various carrier’s particle and bulk properties, device type and airflow were investigated in silico. Results showed that for the capsule-based device, low-dose blends of SS had a better performance, when smaller carrier particles (Dv0.5 ≈ 50 μm) with about 10% of fines were used. This resulted in a better predicted bioavailability of the drug for all the tested airflows. For the reservoir type DPI, the mean particle size (Dv0.5) was identified as the critical parameter impacting performance. Shear cell and air permeability or compressibility measurements, particle size distribution by pressure titration and the tensile strength of the selected lactose carrier powders were found useful to generate descriptors that could anticipate the potential in vivo performance of the tested DPI blends.

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