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The Mycobacterium Tuberculosis infection can be treated via clofazimine (CLF)-loaded nanostructured lipid carriers (NLCs). Precipitation-hot microemulsification-probe sonication method was employed...

The non-modified nanocarriers-based therapies for the treatment of cancer and other infectious diseases enhanced the chemical stability of therapeutically active agents, protected them from enzymatic degradation and extended their blood circulation time. However, the lack of specificity and off-target effects limit their applications. Mannose receptors overexpressed on antigen presenting cells such as dendritic cells and macrophages are one of the most desirable targets for treating cancer and other infectious diseases. Therefore, the development of mannosylated nanocarrier formulation is one of the most extensively explored approaches for targeting these mannose receptors. The present manuscript gives readers the background information on C-type lectin receptors followed by the roles, expression, and distribution of the mannose receptors. It further provides a detailed account of different mannosylated nanocarrier formulations. It also gives the tabular information on most relevant and recently granted patents on mannosylated systems. The overview of mannosylated nanocarrier formulations depicted site-specific targeting, enhanced pharmacokinetic/pharmacodynamic profiles, and improved transfection efficiency of the therapeutically active agents. This suggests the bright future ahead for mannosylated nanocarriers in the treatment of cancer and other infectious diseases. Nevertheless, the mechanism behind the enhanced immune response by mannosylated nanocarriers and their thorough clinical and preclinical evaluation need to explore further.

Verapamil, a calcium channel blocker has poor bioavailability (20-30%) owing to extensive hepatic first-pass metabolism. Hence, the major objective of this research was to improve the oral bioavailability of Verapamil by Solid Lipid Nanoparticles (V-SLNs) using high shear homogenization and ultrasonication technology. A 3

Psoriasis is linked with unusual differentiation and hyperproliferation of epidermal keratinocytes that significantly impair the quality of life (QoL) of patients. The present treatment options only provide symptomatic relief and are surrounded by various adverse effects. Recently, nanostructured lipid carriers (NLCs) have emerged as next-generation nanocarriers with better physicochemical characteristics. The current manuscript provides background information on psoriasis, its pathophysiology, existing treatment options, and its limitations. It highlights the advantages, rationale, and mechanism of the permeation of NLCs for the treatment of psoriasis. It further gives a detailed account of various NLC nanoformulations for the treatment of psoriasis. In addition, tabular information is provided on the most relevant patents on NLCs for treating psoriasis. Lastly, light is shed on regulatory considerations related to NLC-like nanoformulations. In the treatment of psoriasis, NLCs display a sustained release drug profile, an ability to incorporate both hydrophobic and hydrophilic drugs, an enhancement in skin hydration, penetrability, retention, and bioavailability of the drug, along with reduced staining potential as compared to conventional ointments, and decreased side effects of drug molecules. This affirms the bright future of NLC nanoformulations in the treatment of psoriasis. However, academic industry collaboration and more sound regulatory controls are required to commercialize the NLC nanoformulations for psoriasis treatment.

Tuberculosis (TB) disease is caused due to the infection of Mycobacterium tuberculosis bacilli which reside in alveolar macrophages (AMs). Clofazimine (CLF) has been reinstated clinically for the t...

Pulmonary tuberculosis (TB) is a leading cause of death worldwide and is caused by the pathogen Mycobacterium tuberculosis (MTb). As treatment for TB, dry powders for inhalation (DPIs) are considered stable compared with nebulizers and metered dose inhalers and are suitable for high-dose formulations. Although extensive research has been done over the last two to three decades on nanocarrier-based DPIs for targeting MTb infection, none of the anti-TB DPI formulations have reached the market. Challenges in the proper assessment of nanocarrier-based DPIs due to the complexity of lungs is one of the reasons. In this review, the details of in vitro evaluation parameters of nanocarriers and nanocarrier-based DPIs along with their need and basic principles are discussed. Further, the thorough in vitro, ex vivo, and in vivo pharmacological evaluations, together with their procedures wherever required, are covered. The different evaluation parameters during process development, release specifications, and stability studies suggested by U.S. Food and Drug Administration Center for Drug Evaluation and Research to apply for new drug applications and abbreviated new drug applications of DPIs are also discussed. Lastly, the evaluation parameters for DPIs provided in European, United States, British, and Indian pharmacopeias are summarized.

The present research work discusses the systematic Quality by Design (QbD) enabled development of a simple, rapid, economical, and stability-indicating high-performance liquid chromatography (HPLC) method for effective analysis of clofazimine (CFZ). An Ishikawa fish-bone diagram was constructed for initial risk assessment. Analytical target profile (ATP) was defined and critical analytical attributes (CAAs) were assigned to meet these ATP requirements. Taguchi design was applied for screening critical material attributes (CMAs) and critical process parameters (CPPs) making an impact on the assigned CAAs. The major contributing factors were finely tuned using 33 Box-Behnken design with numerical and graphical optimization. Further, the method was validated as per the ICH guidelines and force degradation studies were carried out under different stress conditions. The optimum chromatographic separation was accomplished using 75:25% v/v ratio of methanol and ammonium acetate buffer (0.01 mol/L) as the mobile phase at flow rate 1.0 mL/min, and UV detection at 284 nm. The developed HPLC method was found highly sensitive, specific with linearity ranging between 2 and 10 µg/mL, and correlation coefficient (R2) 0.9995. It showed high accuracy with % recovery between 99.68 and 100.44%. It depicted detection limit and quantitation limit of 0.0066 µg/mL and 0.0199 µg/mL, respectively. In force degradation studies the drug was found to be highly susceptible in alkaline stress conditions. The results reveal successful applicability of the method for the estimation of CFZ from its marketed formulation which can be wisely extrapolated to assess the CFZ from its other formulation systems and different biological samples.

Introduction Tuberculosis (TB) is a disease caused due to an infection of Mycobacterium tuberculosis (M TB) bacilli affecting millions of people worldwide. It is the ninth leading cause of death and ranks above the HIV/AIDS. The unique intracellular life cycle, more dangerous drug-resistant forms of bacilli, and insufficient investments in the TB research and development hindered the occurrence of optimum diagnostic, preventive, and treatment strategy against this disease. Areas covered The aim of this review is to provide an update and overview of the current trends in the diagnosis, prevention, and treatment of the disease. It summarizes a recent patent literature (2014-2017) available on the same. Expert opinion Some questions like 'why most of these inventions do not reach up to the market for public use? Are these inventions being explored only to get a financial return to a particular industry or do they have any societal benefit?' emphatically come to mind. Together with the efforts taken by various governmental and nongovernmental organizations, a public awareness about the recent advancements in the diagnosis and treatment of the disease is of the highest importance to make 'the end of TB' from the universe.

According to the list published by the WHO for global top ten causes of death, lung diseases contribute nearly one-third of the total mortality. The current treatment on lung diseases provide only symptomatic relief rather than restoring the complete lung functions. Nanostructured lipid carriers-based drug delivery system (NLCs-based DDS) provide a breakthrough in treating various lung diseases. This review provides the readers with background information for rationale behind focusing lung diseases and selection of targeted drug delivery to treat these diseases. This review discusses different hurdles in targeting the lung diseases and possible remedy in the form of NLCs-based DDS. The review gives an overview of the existing literature about the quality, safety, and efficacy of the NLCs-based DDS for pulmonary targeting. Different surface-engineered NLCs enormously proved their effectiveness in targeting the drug and other bioactive agents to the site of infection. Their results of safety and efficacy studies in in-vitro and in-vivo evaluations are encouraging. This advises the bright future of NLCs-based DDS for pulmonary targeting. To bring this optimistic NLCs-based DDS to the market, a thorough pre-clinical and clinical investigation hold prime importance.

Clofazimine (CFZ), a riminophenazine derivative and a crucial drug in the treatment of lepromatous leprosy, has been reintroduced clinically to treat multidrug-resistant tuberculosis. CFZ holds both antimycobacterial and anti-inflammatory properties. But, due to its highly hydrophobic, polar and photosensitive nature, it is challenging to extract and quantify the drug from different biological fluids and its pharmaceutical formulations. This has also hampered the pharmacokinetic evaluation of the CFZ. This article accentuates various analytical methods viz. Identification methods, titrimetric methods, spectrometric methods such as colorimetric, fluorometric, mass spectroscopy and UV/Vis spectroscopy, Chromatographic methods like paper chromatography, thin-layer chromatography, high-performance thin layer chromatography, high-performance liquid chromatography, liquid chromatography tandem mass spectrometry for the estimation of CFZ in bulk, biological fluids and its pharmaceutical formulations.

Tuberculosis (TB) is a disease caused by the pathogen Mycobacterium tuberculosis. Prolonged administration of high dose antibiotics using oral and injectable routes and their associated side effects show limitations to successful treatment outcome of TB. Nanocarrier-based dry powder inhalers (DPIs) may provide a breakthrough as an alternative therapeutic approach because of their stable, non-invasive nature and ability to target the drug at the site of infection. The current review focuses on the roadmap of the respiratory system, drug deposition and targeting at the site of infection via the pulmonary route. This review will provide readers with an overview of the existing literature of nanocarrier-based DPIs of anti-TB drugs. Among different nanocarriers, results of most of the proliposomes and polymeric particles-based DPIs with respect to their characterisation parameters like encapsulation efficiency, drug loading, storage stability and aerodynamic properties are not encouraging, whereas surface engineered, nanostructured lipid carriers (NLCs), i.e. ligand attached-NLCs-based dry powder inhalers (NLCs-DPI) show promising results. But still, there is a need to investigate them for in vitro, ex vivo, in vivo and toxicity studies to achieve a market approval.

The Mycobacterium Tuberculosis infection can be treated via clofazimine (CLF)-loaded nanostructured lipid carriers (NLCs). Precipitation-hot microemulsification-probe sonication method was employed for formulation of CLF-NLCs and optimised by using 33 Box–Behnken design. The surface of CLF-NLCs was modified with mannose ligands. The mannose modified and bare CLF-NLC formulations show highest encapsulation efficiencies greater than 70%. The preliminary evaluations were performed by using analytical techniques like Fourier transform infrared spectroscopy, differential scanning colorimetry, and powder X-ray diffraction studies. In-vitro drug release studies showed pH-dependent, sustained drug release profiles and best fitted for first order and Higuchi kinetics. The spherical morphologies of NLCs were confirmed by field-emission scanning electron microscopy. The formulations showed high storage stability at ambient and refrigerated conditions. Thus, present research successfully demonstrated the application of QbD principles in developing CLF-NLCs and improved the performance of CLF.

Nanocarriers, and nanotechnology have been studied extensively for oral drug delivery. An important characteristic of active pharmaceutical ingredient (API) nanocrystal is that it is totally composed of API only and no other carrier material is required. This chapter describes the application of nanoparticulate drug and/or delivery system for oral administration. The extent of solubility of a drug in a given solvent is measured as the saturation concentration where further addition of solid drug does not increase its concentration in the solution. The slow dissolution process of the poorly water-soluble drugs is the major factor of its poor bioavailability. Co-solvents are used to enhance the solubilization, solvent capacity and aid in the self-emulsification of the system. They aid the dissolution of hydrophilic surfactants. Various drug molecules can be incorporated into Solid Lipid Nanoparticles (SLNs). Three different models are mentioned in the literature for drug incorporation into SLNs as follows: Solid solution model; drug enriched shell model; and drug enriched core model.