Preparation and Evaluation of Low-Dose Calcitriol Dry Powder Inhalation as Host-Directed Adjunct Therapy for Tuberculosis.

ABSTRACT:

Background

It is unclear whether Vitamin D is efficacious as a host-directed therapy (HDT) for patients of tuberculosis (TB). We investigated pulmonary delivery of the active metabolite of Vitamin D₃, i.e., 1, 25-dihydroxy vitamin D₃ (calcitriol) in a mouse model of infection with Mycobacterium tuberculosis (Mtb).

Methods

We optimized a spray drying process to prepare a dry powder inhalation (DPI) of calcitriol using a Quality by Design (QbD) approach. We then compared outcomes when Mtb-infected mice were treated with inhaled calcitriol at 5 ng/kg as a stand-alone intervention versus DPI as adjunct to standard oral anti-tuberculosis therapy (ATT).

Results

The DPI with or without concomitant ATT markedly improved the morphology of the lungs and mi

SUBMITTER: Reddy DVS 

PROVIDER: S-EPMC9374297 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature