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. 2022 Jan 18:3:100084.
doi: 10.1016/j.crphar.2022.100084. eCollection 2022.

Inhalation potential of N-Acetylcysteine loaded PLGA nanoparticles for the management of tuberculosis: In vitro lung deposition and efficacy studies

Vishal Puri  1 , Kabi Raj Chaudhary  1 , Arti Singh  2 , Charan Singh  1
Affiliations

Inhalation potential of N-Acetylcysteine loaded PLGA nanoparticles for the management of tuberculosis: In vitro lung deposition and efficacy studies

Vishal Puri et al. Curr Res Pharmacol Drug Discov. .

Abstract

Several studies have stated that mucus is a critical hurdle for drug delivery to the mucosal tissues. As a result, Polymeric nanoparticles that can overcome mucus barriers are gaining popularity for controlled drug delivery into intra-macrophages to attain high intracellular drug concentration. The present study was aimed to fabricate inhalable N-acetylcysteine (NAC) modified PLGA mucus penetrating particles using the double emulsion method (w/o/w) for target delivery to alveolar macrophages and minimize the dose-related adverse effects, efficiently encapsulate hydrophilic drug, sustain the release profile and prolong the retention time for the management of tuberculosis. Among the numerous formulations, the drug/polymer ratio of 1:10 with 0.50% PVA concentration and sonication time for 2 ​min ​s was chosen for further research. The formulated nanoparticles had a mean particle size of 307.50 ​± ​9.54 ​nm, PDI was 0.136 ​± ​0.02, zeta potential about -11.3 ​± ​0.4 ​mV, decent entrapment efficiency (55.46 ​± ​2.40%), drug loading (9.05 ​± ​0.22%), and excellent flowability. FTIR confirmed that NAC and PLGA were compatible with each other. SEM graphs elucidated that the nanoparticles were spherically shaped with a slightly rough surface whereas TEM analysis ensured the nanometer size nanoparticles and coating of lipid over NPs surface. PXRD spectrum concluded the transformation of the drug from crystalline to amorphous state in the formulation. In vitro release pattern was biphasic started with burst release (64.67 ​± ​1.53% within 12hrs) followed by sustained release over 48hrs thus enabling the prolonged replenishing of NAC. In vitro lung deposition study pronounced that coated NAC-PLGA-MPPs showed favorable results in terms of emitted dose (86.67 ​± ​2.52%), MMAD value (2.57 ​± ​0.12 ​μm), GSD value (1.55 ​± ​0.11 ​μm), and FPF of 62.67 ​± ​2.08% for the deposition and targeting the lungs. Finally, in vitro efficacy studies demonstrated that NAC-PLGA-MPPs presented more prominent antibacterial activity against MTB H37Rv strain as compared to NAC. Hence, PLGA based particles could be a better strategy to deliver the NAC for lung targeting.

Keywords: Inhalation; Lung targeting; N-Acetylcysteine; PLGA; Pluronic F-127; Tuberculosis.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Schematic representation of nanoparticles (A) without coated with Pluronic F127 (B) coated with Pluronic F127.
Fig. 2
Fig. 2
Fourier transform infrared (FTIR) spectrum of (A) pure NAC (B) PLGA (C) physical mixture of NAC-PLGA-F127 and (D) NAC-PLGA-MPPs.
Fig. 3
Fig. 3
Differential scanning calorimetric (DSC) thermograms of (A) NAC (B) PLGA (C) NAC-PLGA-F127 and (D) NAC-PLGA-MPPs.
Fig. 4
Fig. 4
Scanning electron micrographs (SEM) images of (A) Uncoated NAC-PLGA-MPPS and (B) Coated NAC-PLGA-MPPs.
Fig. 5
Fig. 5
Transmission electron microphotograph (TEM) of (A) Uncoated NAC-PLGA-MPPS and (B) Coated NAC-PLGA-MPPs.
Fig. 6
Fig. 6
X-ray diffraction data of (A) NAC (B) PLGA (C) NAC-PLGA-F127 (D) NAC-PLGA-MPPs. PM stands for the physical mixture.
Fig. 7
Fig. 7
Comparative in vitro release pattern of NAC and optimized NAC-PLGA-MPPs (n ​= ​3).
Fig. 8
Fig. 8
In vitro aerosol deposition profile of uncoated and coated NAC-PLGA-MPPs on each stage following next-generation impactor (NGI) (mean ​± ​SD, n ​= ​3).
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