Delivery Of Antitubercular Drugs Research Articles

Mannose-Decorated Solid-Lipid Nanoparticles for Alveolar Macrophage Targeted Delivery of Rifampicin.

Alveolar macrophages play a vital role in a variety of lung diseases, including tuberculosis. Thus, alveolar macrophage targeted anti-tubercular drug delivery through nanocarriers could improve its therapeutic response against tuberculosis. The current study aimed at exploring the efficacy of glyceryl monostearate (GMS)-based solid-lipid nanoparticles (SLNs) and their mannose functionalized forms on the alveolar macrophage targeting ability of an anti-tubercular model drug, rifampicin (Rif). Rif-loaded SLNs were accomplished by the solvent diffusion method. These carriers with unimodal particle size distribution (~170 nm) were further surface-modified with mannose via Schiff-base reaction, leading to slight enhancement of particle diameter and a decline of drug loading capacity. The encapsulated Rif, which was molecularly dispersed within the matrices as indicated by their XRD patterns, was eluted in a sustained manner with an initial burst release effect. The uptake efficiency of mannose-modified SLNs was remarkably higher than that of corresponding native forms on murine macrophage Raw 264.7 cells and human lung adenocarcinoma A549 cells. Eventually, the mannose-modified SLNs showed a greater cytotoxicity on Raw 264.7 and A549 cells relative to their unmodified forms. Overall, our study demonstrated that mannose modification of SLNs had an influence on their uptake by alveolar macrophages, which could provide guidance for the future development of alveolar macrophage targeted nanoformulations.

Fusion Landscape of Mycobacterial Envelope-Derived Lipid Vesicles with Intact Bacteria Dictates High Intracellular Drug Retention.

Membrane vesicles are critical regulators of pathogenic diseases. In tubercular infections, the use of mycobacteria derived vesicles as delivery vehicles to overcome drug resistance and complex treatment regimens has never been attempted. Here, we first address how these vesicles interact with their target cells, especially via membrane fusion. Membrane fusion between alike mycobacterial outer and inner membrane layer-derived lipid vesicles is shown to be driven by the structural, geometrical, and biophysical attributes of constituent lipids. The increased fusion of outer-membrane-derived vesicles with intact bacteria ensures enhanced intracellular drug levels and is presented as a "natural" antitubercular drug delivery vehicle.

Nanocarrier-Based Approaches for the Efficient Delivery of Anti-Tubercular Drugs and Vaccines for Management of Tuberculosis.

Drug-resistant species of tuberculosis (TB), which spread faster than traditiona TB, is a severely infectious disease. The conventional drug therapy used in the management of tuberculosis has several challenges linked with adverse effects. Hence, nanotherapeutics served as an emerging technique to overcome problems associated with current treatment. Nanotherapeutics helps to overcome toxicity and poor solubility issues of several drugs used in the management of tuberculosis. Due to their diameter and surface chemistry, nanocarriers encapsulated with antimicrobial drugs are readily taken up by macrophages. Macrophages play a crucial role as they serve as target sites for active and passive targeting for nanocarriers. The surface of the nanocarriers is coated with ligand-specific receptors, which further enhances drug concentration locally and indicates the therapeutic potential of nanocarriers. This review highlights tuberculosis’s current facts, figures, challenges associated with conventional treatment, different nanocarrier-based systems, and its application in vaccine development.

Application of Lipid-Based Nanocarriers for Antitubercular Drug Delivery: A Review.

The antimicrobial drugs currently used for the management of tuberculosis (TB) exhibit poor bioavailability that necessitates prolonged treatment regimens and high dosing frequency to achieve optimal therapeutic outcomes. In addition, these agents cause severe adverse effects, as well as having detrimental interactions with other drugs used in the treatment of comorbid conditions such as HIV/AIDS. The challenges associated with the current TB regimens contribute to low levels of patient adherence and, consequently, the development of multidrug-resistant TB strains. This has led to the urgent need to develop newer drug delivery systems to improve the treatment of TB. Targeted drug delivery systems provide higher drug concentrations at the infection site, thus leading to reduced incidences of adverse effects. Lipid-based nanocarriers have proven to be effective in improving the solubility and bioavailability of antimicrobials whilst decreasing the incidence of adverse effects through targeted delivery. The potential application of lipid-based carriers such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, nano and microemulsions, and self-emulsifying drug delivery systems for the treatment of TB is reviewed herein. The composition of the investigated lipid-based carriers, their characteristics, and their influence on bioavailability, toxicity, and sustained drug delivery are also discussed. Overall, lipid-based systems have shown great promise in anti-TB drug delivery applications. The summary of the reviewed data encourages future efforts to boost the translational development of lipid-based nanocarriers to improve TB therapy.

Porous particles and novel carrier particles with enhanced penetration for efficient pulmonary delivery of antitubercular drugs

This study aimed to design dry powder inhaler formulations using a hydrophilic polymeric polysaccharide, phytoglycogen (PyG), as a multi-functional additive that increases the phagocytic activity of macrophage-like cells and enhances pulmonary delivery of drugs. The safety and usefulness of PyG were determined using in vitro cell-based studies. Dry powder inhaler formulations of an antitubercular drug, rifampicin, were fabricated by spray drying with PyG. The cytotoxicity, effects on phagocytosis, particle size, and morphology were evaluated. The aerosolization properties of the powder formulations were evaluated using an Andersen cascade impactor (ACI). Scanning electron microscope images of the particles on each ACI stage were captured to observe the deposition behavior.PyG showed no toxicity in A549, Calu-3, or RAW264.7 cell lines. At concentrations of 0.5 and 1 g/L, PyG facilitated the cellular uptake of latex beads and the expression of pro-inflammatory cytokine genes in RAW264.7 cells. Formulations with outstanding inhalation potential were produced. The fine particle fraction (aerodynamic size 2–7 µm) of the porous particle batch reached nearly 60%, whereas in the formulation containing wrinkled carrier particles, the extra-fine particle fraction (aerodynamic particle size < 2 μm) was 25.0% ± 1.7%. The deposition of porous and wrinkled particles on individual ACI stages was distinct. The inclusion of PyG dramatically improved the inhalation performance of porous and wrinkled powder formulations. These easily inhaled immunostimulatory carrier particles may advance the state of research by enhancing the therapeutic effect and alveolar delivery of antitubercular drugs.

Engineering of konjac glucomannan into respirable microparticles for delivery of antitubercular drugs

Few medically-approved excipients are available for formulation strategies to endow microcarriers with improved performance in lung drug targeting. Konjac glucomannan (KGM) is a novel, biocompatible material, comprising mannose units potentially inducing macrophage uptake for the treatment of macrophage-mediated diseases. This work investigated spray-dried KGM microparticles as inhalable carriers of model antitubercular drugs, isoniazid (INH) and rifabutin (RFB). The polymer was characterised and different polymer/drug ratios tested in the production of microparticles for which respirability was assessed in vitro. The swelling of KGM microparticles and release of drugs in simulated lung fluid were characterised and the biodegradability in presence of β-mannosidase, a lung hydrolase, determined. KGM microparticles were drug loaded with 66–91% association efficiency and had aerodynamic diameter around 3 µm, which enables deep lung penetration. The microparticles swelled upon liquid contact by 40–50% but underwent size reduction (>62% in 90 min) in presence of β-mannosidase, indicating biodegradability. Finally, drug release was tested showing slower release of RFB compared with INH but complete release of both within 24 h. This work identifies KGM as a biodegradable polymer of natural origin that can be engineered to encapsulate and release drugs in respirable microparticles with physical and chemical macrophage-targeting properties.

Activation of benzoate model prodrugs by mycobacteria. Comparison with mammalian plasma and liver hydrolysis

Due to difficulties in drug penetration in M. tuberculosis, a prodrug approach based on mycobacterial activation appears as a promising strategy to increase the delivery of antitubercular drugs to the target microorganisms. Esters have been successful used by us and others to deliver drugs to mycobacteria, however because very little is known about the metabolic hydrolysis of esters by mycobacteria in connection with prodrug activation, we decided to study the process further. For that we selected a series of 13 benzoates with different chain lengths and ramifications in the alkoxy side as model prodrugs and examined their hydrolysis by a mycobacterial homogenate, comparing the results with those obtained parallelly in human plasma and in total rat liver homogenate. In all biological media, the benzoates with a linear alkyl group showed a parabolic dependence between log(k) and logP (or the number of carbons of the linear alkyl chain) that reached a maximal value for the n-butyl chain. Considering linear correlations for the total number of compounds between log(k) and chosen descriptors, for mycobacterial esterases, pKa of the leaving alcohol (pKaLG) seem to be the most important descriptor. Plasma esterases seem to be quite sensitive to the Taft polarity parameter σ* and also to pKaLG and less sensitive to steric effects. Liver esterases seem to be more sensitive to the Taft steric descriptor ESc. Lipophilicity correlates weakly with log(k) in all the 3 media, however, is more important when one looks for mycobacterial activation selectivity in relation to plasma metabolism or in relation to liver homogenate metabolism. The importance of lipophilicity increases further when biparametric expressions are considered. We showed that it is easy to activate a wide variety of benzoate esters using a mycobacterial homogenate. The data also suggest that with careful design is possible to obtain tuberculostatic prodrug esters sensitive to mycobacterial hydrolases while reasonably resistant to plasma and liver hydrolysis. One important observation is that mycobacterial hydrolysis is less affected by bulky substituents than liver homogenate or plasma hydrolysis. tert-Butyl is probably the substituent in the alkoxy side that seems more adequate to resist simultaneously plasma and liver metabolism, while allowing activation by mycobacterial esterases. Hexyl is also a good option for the medicinal chemist if a linear alkoxy chain is needed.

Resistant Tuberculosis: the Latest Advancements of Second-line Antibiotic Inhalation Products.

Drug-resistant tuberculosis (TB) can be considered the man-made result of interrupted, erratic or inadequate TB therapy. As reported in WHO data, resistant Mycobacterium tuberculosis (Mtb) strains continue to constitute a public health crisis. Mtb is naturally able to survive host defence mechanisms and to resist most antibiotics currently available. Prolonged treatment regimens using the available first-line drugs give rise to poor patient compliance and a rapid evolution of strains resistant to rifampicin only or to both rifampicin and isoniazid (multi drug-resistant, MDR-TB). The accumulation of mutations may give rise to extensively drug-resistant strains (XDR-TB), i.e. strains with resistance also to fluoroquinolones and to the injectable aminoglycoside, which represent the second-line drugs. Direct lung delivery of anti-tubercular drugs, as an adjunct to conventional routes, provides high concentrations within the lungs, which are the intended target site of drug delivery, representing an interesting strategy to prevent or reduce the development of drug-resistant strains. The purpose of this paper is to describe and critically analyse the most recent and advanced results in the formulation development of WHO second-line drug inhalation products, with particular focus on dry powder formulation. Although some of these formulations have been developed for other lung infectious diseases (Pseudomonas aeruginosa, nontuberculous mycobacteria), they could be valuable to treat MDR-TB and XDR-TB.

A Novel Method for Preparing Uniform-Sized PLGA Microspheres and the Application in Anti-tubercular Drug Delivery

The size was a key factor influencing the drug loading, release, and delivery efficacies of poly (lactic-co-glycolic) acid (PLGA) microspheres (MS). The purpose of the study was to explore a novel and simple method to prepare uniform-sized PLGA MS for drug delivery. Different from routine homogenizer, a vortex shaker was employed for emulsification during the preparation of PLGA MS. To enhance the homogeneity of resulted PLGA MS, a glass bead was used to facilitate the emulsification. The size of PLGA MS was controlled by adjusting the working frequency and time of vortex shaker. Then, selective centrifugation was used to further enrich PLGA MS of desired size. The resulted PLGA MS were systematically evaluated in anti-tubercular drug delivery. Compared with the routine stirring-based method, the novel method possessed a higher efficiency of emulsification and resulted in more homogenous MS under similar conditions. The produced PLGA particles were of a narrow size distribution, which could be 1 to 5 μm by adjusting the working frequency and time of vortex shaker. The narrow size distribution made it rather easy to enrich PLGA MS of specific size through selective centrifugation. Then, to evaluate the potential of the PLGA MS for drug delivery, 2–3-μm sized PLGA MS were selected to deliver anti-tubercular drug rifampicin (RFP). In vitro experiments demonstrated that the loaded RFP could be well-controlled release and delivered into macrophages. Anti-tubercular experiments showed that the uniform-sized MS as carriers of RFP significantly enhanced the therapeutic efficacy of the drug. Collectively, the study provided a novel and simple method for preparing uniform-sized PLGA MS, which may be of potentially wide applications.

Nano-based anti-tubercular drug delivery: an emerging paradigm for improved therapeutic intervention.

Tuberculosis (TB) classified as one of the most fatal contagious diseases is of prime concern globally. Mycobacterium tuberculosis is the causative agent that ingresses within the host cells. The approved conventional regimen, though the only viable option available, is unfavorably impacting the quality of life of the affected individual. Despite newer antibiotics gaining light, there is an unending demand for more therapeutic alternatives. Therefore, substantial continuous endeavors are been undertaken to come up with novel strategies to curb the disease, the stepping stone being nanotechnology. This approach is instrumental in overcoming the anomalies associated with conventional therapy owing to their intriguing attributes and leads to optimization of the therapeutic effect to a certain extent. This review focusses on the different types of nanocarrier systems that are being currently explored by the researchers for the delivery of anti-tubercular drugs, the outcomes achieved by them, and their prospects. Graphical abstract

Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: Therapeutic assessment in a murine model of tuberculosis infection

Tuberculosis is a leading cause of death worldwide. Although the development of new antimycobacterial drugs is an obvious and necessary strategy to address the disease, improving the therapeutic performance of drugs already approved constitutes a valuable alternative approach. As the lung is the most affected organ, where M. tuberculosis is able to survive and proliferate, the direct pulmonary delivery of antitubercular drugs comprises a highly promising therapeutic strategy. In this work, spray-dried locust bean gum (LBG) microparticles were used to deliver a combination of two first line antitubercular drugs, isoniazid (INH) and rifabutin (RFB), to the alveolar zone, where macrophages hosting the bacteria reside. LBG is expected to mediate favoured macrophage uptake of microparticles, leading to enhanced therapeutic effect. The therapeutic effect of LBG/INH/RFB microparticles was evaluated in a murine model infected with M. tuberculosis, strain H37Rv and compared with oral co-therapy of INH and RFB in the free form. The pulmonary administration of LBG/INH/RFB microparticles 5 times per week was the only treatment schedule that provided negative growth index values in lung (−0.22), spleen (−0.14) and liver (−0.26) even using a lower therapeutic dose for both antibiotics. For the control group, the respective values were +1.95, +0.75 and +0.96.

Synthesis and Characterization of pH-Sensitive Inulin Conjugate of Isoniazid for Monocyte-Targeted Delivery.

The use of particles for monocyte-mediated delivery could be a more efficient strategy and approach to achieve intracellular targeting and delivery of antitubercular drugs to host macrophages. In this study, the potential of inulin microparticles to serve as a drug vehicle in the treatment of chronic tuberculosis using a monocytes-mediated drug targeting approach was evaluated. Isoniazid (INH) was conjugated to inulin via hydrazone linkage in order to obtain a pH-sensitive inulin-INH conjugate. The conjugate was then characterized using proton nuclear magnetic resonance (1HNMR), Fourier transform infrared spectroscopy (FTIR) as well as in vitro, cellular uptake and intracellular Mycobacterium tuberculosis (Mtb) antibacterial efficacy. The acid-labile hydrazone linkage conferred pH sensitivity to the inulin-INH conjugate with ~95, 77 and 65% of the drug released after 5 h at pH 4.5, 5.2, and 6.0 respectively. Cellular uptake studies confirm that RAW 264.7 monocytic cells efficiently internalized the inulin conjugates into endocytic compartments through endocytosis. The intracellular efficacy studies demonstrate that the inulin conjugates possess a dose-dependent targeting effect against Mtb-infected monocytes. This was through efficient internalization and cleavage of the hydrazone bond by the acidic environment of the lysosome, which subsequently released the isoniazid intracellularly to the Mtb reservoir. These results clearly suggest that inulin conjugates can serve as a pH-sensitive intracellular drug delivery system for TB treatment.

Development &amp; Pharmaceutical Characterization of Isoniazid Loaded Solid Lipid Nanoparticle Drug Delivery Approach

Background: Tuberculosis is a major public health problem in the world. Isoniazid is a first line antitubercular drug active against Mycobacterium species which inhibits mycolic acid synthesis. Objective: The aim of the present investigation was the preparation of solid lipid nanoparticle containing Isoniazid to increase bioavailability, sustained release and decrease toxicity by increasing permeability. Methods: Isoniazid was incorporated into SLN for sustained drug delivery, increasing permeability and bioavailability. SLNs were prepared by emulsification followed by the solvent evaporation technique by optimizing lipid, polymer and surfactant ratio under controlled optimized process variables i.e. temperature and stirring speed. SLNs were characterized for particle size analysis, comparative study design in different physiological pH for in-vitro drug release and drug release kinetics. Results: The best in-vitro release for F7 was found to be 80.2% in pH-7.4 and 82.2% in pH-4.5. The particle size of the F7 formulation was found to be in the range of 200- 600nm . Among all 3 optimized formulations, i.e. F3, F7 and F8 in both the pH, F3 followed non-fickian diffusion mechanism in pH-4.5 whereas all the formulations in both pH followed super-case II diffusion mechanism. The stability studies were carried out as per ICH guidelines which signify that the SLNs were found stable in the refrigerated condition. Conclusion: The results clearly demonstrated that SLNs drug delivery system is a promising approach for antitubercular drug delivery as it proved to sustained release, increase permeability, enhanced bioavailability and thus decreased dosing frequency. Kinetic modelling of the formulation with zero, first order, Higuchi and Korsmeyer- peppas is explained in this article.

Encapsulation of Isoniazid-conjugated Phthalocyanine-In-Cyclodextrin-In-Liposomes Using Heating Method

Liposomes are reputed colloidal vehicles that hold the promise for targeted delivery of anti-tubercular drugs (ATBDs) to alveolar macrophages that host Mycobacterium tuberculosis. However, the costly status of liposome technology, particularly due to the use of special manufacture equipment and expensive lipid materials, may preclude wider developments of therapeutic liposomes. In this study, we report efficient encapsulation of a complex system, consisting of isoniazid-hydrazone-phthalocyanine conjugate (Pc-INH) in gamma-cyclodextrin (γ-CD), in liposomes using crude soybean lecithin by means of a simple organic solvent-free method, heating method (HM). Inclusion complexation was performed in solution and solid-state, and evaluated using UV-Vis, magnetic circular dichroism, 1H NMR, diffusion ordered spectroscopy and FT-IR. The HM-liposomes afforded good encapsulation efficiency (71%) for such a large Pc-INH/γ-CD complex (PCD) system. The stability and properties of the PCD-HM-liposomes look encouraging; with particle size 240 nm and Zeta potential −57 mV that remained unchanged upon storage at 4 °C for 5 weeks. The release study performed in different pH media revealed controlled release profiles that went up to 100% at pH 4.4, from about 40% at pH 7.4. This makes PCD-liposomes a promising system for site-specific ATBD delivery, and a good example of simple liposomal encapsulation of large hydrophobic compounds.

3D printed mesoporous bioactive glass/metal-organic framework scaffolds with antitubercular drug delivery

Three-dimensional (3D) porous scaffolds with sustained drug delivery are pursued for osteoarticular tuberculosis therapy after surgery. In this study, mesoporous bioactive glass/metal-organic framework (MBG/MOF) scaffolds with sustained antitubercular drug release have been fabricated by 3D printing. The results showed that the MBG/MOF scaffolds possess macropores of ca. 400 μm and enhanced compressive strength of 3–7 MPa, also exhibited good biocompatibility and apatite forming ability in vitro. Furthermore, the drug release rate and pH microenvironment of the MBG/MOF scaffolds could be controlled due to the MOF degradation. These results indicated that the 3D printed MBG/MOF scaffolds are promising for treating osteoarticular tuberculosis.

Inhalable Fucoidan Microparticles Combining Two Antitubercular Drugs with Potential Application in Pulmonary Tuberculosis Therapy.

The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6–3.9 µm. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.

Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular drugs

Pulmonary tuberculosis accounts for 80% of cases and the delivery of antitubercular drugs into the lungs allows targeting the infected organ and, possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as matrix of inhalable microparticles that associate two first-line antitubercular drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed of fucose and sulphated sugar residues, moieties described as being recognised by surface receptors of alveolar macrophages, which host mycobacteria. Inhalable fucoidan microparticles loaded with antitubercular drugs were successfully produced with high association efficiencies of either isoniazid (95%) or rifabutin (81%). The microparticles evidenced no cytotoxicity on lung epithelial cells (A549). However, rifabutin-loaded microparticles showed a certain degree of toxicity on macrophage-like cells (THP-1) at the highest tested concentration (1 mg/mL). Furthermore, microparticles showed favourable aerodynamic properties for deep lung delivery (MMAD 2.0–3.8 µm) and, thus, show potential for an application as inhalable tuberculosis therapy.

Macrophage Targeted Cellular Carriers for Effective Delivery of Anti-Tubercular Drugs.

Newly developed vaccine VPM1002 confers paradigm swing in the prophylactic treatment of tuberculosis (TB). Multi-drug resistant and latent TB in adults as well as in underprivileged patients is instigating menace over world population if the host is immune-compromised. One third of the world's population is infected with TB. Recently it is estimated around 9.6 million people around the world became sick with TB disease. There were 1.5 million TB-related deaths worldwide. Therefore with the advent in biotechnology and Nano engineering, newly adapted survival molecular mechanism of Mycobacterium tuberculosis, new targets receptors on alveolar macrophages must be explored out for eradication of TB from the globe. Macrophage acts as a reservoir of phagocytic receptors to execute diverse physiological functions as well as to perform defense mechanism. Advances in novel carriers open new era for the treatment of tuberculosis which remains a very substantial global health encumbrance. Different binding receptors especially mannose, folate and scavenger receptors are attractive platform for internalization of therapeutics in alveolar macrophage. Nano-carriers and nano-devices designed after the acquaintance of receptor composition and functioning affords site specific targeting of biodegradable and biocompatible drug delivery systems for the treatment of tuberculosis offering complete cure and patient compliance. This chapter encompasses recent studies on nanocarriers and new treatment strategies for tuberculosis. In spite of the budding benefits of nano carriers, many limitations still remain to be overcome such as poor oral stability, instability in circulation, inadequate tissue distribution as well as toxicity to normal cells.

Xyloglucan based Microspheres for Pulmonary Delivery of Rifabutin Dry Powder Inhaler

Pulmonary delivery of anti-tubercular drugs can be an effective treatment for tuberculosis. The main objective of the present work was to prepare rifabutin loaded xyloglucan microspheres as dry powder inhaler for pulmonary delivery. Xyloglucan is natural polysaccharide with mucoadhesive property and temperature responsive gelling ability allows its application in microspheres development. Xyloglucan microspheres were prepared by using single step spray drying process using lactose. All microsphere formulations were evaluated for various physical properties such as density and flow. On the basis of results of evaluation parameters such as entrapment efficiency, mucoadhesion, swelling and in vitro drug release, microspheres with 2% xyloglucan and 1% lactose monohydrate were found to be most favorable. They possessed morphology and particle size distribution suitable for pulmonary administration. XRD studies reveal amorphous nature of microspheres. In vitro DPI performance demonstrates suitability of xyloglucan based microspheres for pulmonary delivery. In conclusion, it is suggested that this natural polymer based microspheres containing rifabutin DPI formulation could be used as a significant enhanced treatment for TB.

Nano-Based Anti-Tubercular Drug Delivery and Therapeutic Interventions in Tuberculosis.

Nanotechnology has shown great promise in health care offering numerous possibilities to significantly improve diagnosis of many dreadful diseases including Tuberculosis (TB). Nanomedicine has made the current drug regimen more effective against diseases particularly TB with attributes like sustained release, increased half life, higher drug concentrations at target sites, reduced toxicity and lesser side effects. However because of the severity of the disease, there is a strong urge to develop better approaches with some concomitant regimens using nano-particles to diagnose, treat and manage TB patients. The current review highlights some of the evolving strategies in the field of nanomedicine particularly drug delivery offering promising alternative for the current TB regimens. The study also emphasizes upon the need to design more effective nanocarriers which are highly specific, biocompatible and biodegradable as well.