Tuberculosis (TB) had been a leading chronic bacterial infection since decades. Current therapeutic management of Mycobacterium tuberculosis (MTB) is inadequate due to the lengthy course of treatment, drug-related side effects and ill-planned therapy, and these factors can lead to therapeutic failure and the emergence of drug-resistant TB. The Multi-drug-resistant (MDR) TB needs a lengthy course of treatment with secondline antitubercular drugs (ATDs) having higher side effects and cost. The misuse of second-line ATDs may result in extremely drug-resistant (XDR) strain which is very difficult to treat and require high doses of drugs resulting in more toxicity and side effects. This review highlights the need for novel drug delivery for the treatment of drug-susceptible and resistant TB. The characteristics of the nanoparticulate system in ATDs delivery and its approach in the MDR and XDR TB are discussed. The lung is the site of infection in pulmonary TB and the targeted drug delivery to the site of infection helps in achieving increased efficacy with less dose further reducing the side effects and toxicity. The symbiotic association of nanotechnology and pulmonary drug delivery give rise to an efficient inhalable polymer based nanoparticulate system containing ATDs for the better management of drug-susceptible and resistant TB. Various ATDs loaded polymer based nanocarrier systems like Alginate, PLGA, Chitosan and Gelatin nanocarriers are discussed in detail. Thus, this review highlights the current research in pulmonary drug delivery of polymer based ATDs nanomedicine and their importance in control of drug-resistant TB.
<p>ABSTRACT<br />Objective: To prepare Nanoparticulate dosage form having improved drug bioavailability and reduced dosing frequency of antitubercular drugs<br />which will helps in improving patient compliance in the treatment of multi-drug resistant tuberculosis (MDR-TB).<br />Methods: Ionotropic gelation method was used to prepare D-cycloserine (D-CS)-loaded alginate-chitosan nanoparticles, and the particles are<br />characterized by their particle size and morphology using particle size analyzer and scanning electron microscopy (SEM). X-ray diffraction (XRD),<br />differential scanning calorimetry (DSC), and Fourier-transformed infrared (FTIR) studies were used to determine drug-polymer interactions and drug<br />entrapment. Entrapment efficiency, drug loading (DL), particle size, and zeta potential of nanoparticles were also studied. The 2<br /> factorial designs of<br />experiments by Design-Expert<br />®<br /> V9 were used to optimize the particle size and entrapment efficiency of nanoparticles.<br />Results: The optimized batch had shown the entrapment efficiency of 98.10±0.24% and DL of 69.32±0.44% with particle size and zeta potential<br />as 344±5 nm and −42±11.40 mV, respectively. DSC, FTIR, and XRD studies confirmed the drug entrapment within nanoparticle matrix. SEM results<br />showed spherical-shaped particles. Sustained release of drug from the nanoparticles was observed for 24 hrs period. Respirable fraction up to<br />52.37±0.7% demonstrates the formulation suitability for deep lung delivery. Lung inflammatory study showed a less inflammatory response.<br />Conclusion: Ionotropic gelation method can be used to prepare biocompatible particles with a high entrapment efficiency, DL, optimum particle size,<br />and controlled release characteristics, which can serve as a convenient delivery system for D-CS and could be a potential alternative to the existing<br />conventional therapy in MDR-TB.<br />Keywords: Nanoparticles, Alginate, Chitosan, Inhalation, Sustained release, Tuberculosis.<br />3</p>
Shaji and Shaikh: Current Development of Pulmonary Drug DeliveryThe pulmonary drug delivery system offers several merits over other drug delivery systems and therefore, this delivery route has been in prime focus for various applications like local and systemic therapeutics delivery. The overall development of drug delivery system depends on its efficacy, quality and safety and to achieve such attributes there is a need of reliable evaluation methods to test them. This review provides an in-depth analysis of the development in the evaluation of pulmonary drug delivery systems. In vitro methods of testing pulmonary products such as particle morphological studies, powder flow characteristics, moisture content test, aerosol turboelectric characterization, particles interparticulate forces measurement and solid state characterizations were discussed. Particle size and zeta potential measurement and evaluation of aerosol performance such as dose uniformity and aerodynamic particle size distribution were reviewed in detail. The development of dissolution methods for pulmonary products is also elaborated. Various cell culture methods for testing pulmonary products were overviewed. The in vivo testing methods including drug administration systems, drug deposition studies and pharmacokinetic studies and ex vivo testing models were also highlighted. Together an overview of current advancement in evaluation and characterization of pulmonary drug delivery system can be analyzed and studied through this review.
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