Recent Advancements in Topical Anti-Psoriatic Nanostructured Lipid Carrier-Based Drug Delivery.

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.

Nanostructured lipid carrier-mediated lung targeted drug delivery system to enhance the safety and bioavailability of clofazimine.

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 treatment of TB. However, major challenge of using CLF is its severe side-effects after oral administration. The present research was aimed to establish the safety and enhance the bioavailability of CLF by loading it into nanostructured lipid carriers (CLF-NLCs) and mannosylated NLCs (M-CLF-NLCs) to selectively target the drug toward AMs. The safety of CLF-NLCs and M-CLF-NLCs was evaluated by in vitro hemocompatibility studies, cell viability studies on macrophage J774 cell lines, and in vivo acute inhalation toxicity studies. The bioavailability was estimated by single-dose pharmacokinetics and biodistribution studies. Hemocompatibility studies showed normal RBCs count and least hemolysis of 0.23 ± 0.081% for M-CLF-NLCs treated group. Cell viability studies revealed greater safety of NLCs than CLF-drug dispersion in the concentration range of 2.5-25 µg/ml. In vivo acute toxicity studies revealed no physiological or behavioral changes and no mortality recorded over 14 days period. In pharmacokinetic studies, a maximum concentration of the drug (Cmax) of 35.44 ± 0.34 µg/g from M-CLF-NLCs after 48 h and longer residence time in lung tissues observed due to its sustained release and mannose receptor-mediated endocytosis. M-CLF-NLCs showed a maximum AUC0-∞ value of 2691.83 h µg/ml in lungs that indicated twofold greater bioavailability as compared to CLF-drug dispersion. Thus, mannosylated NLCs can be used as promising carriers for the safe and effective delivery of CLF via inhalation route for the management of TB disease.

Verapamil hydrochloride loaded solid lipid nanoparticles: Preparation, optimization, characterisation, and assessment of cardioprotective effect in experimental model of myocardial infarcted rats.

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 32 factorial design was employed to statistically optimize the formulation to get minimum particle size with maximum entrapment efficiency. The average particle size was 218 nm and the entrapment efficiency was 80.32%. The V-SLN formulation exhibited biphasic behavior with a rapid release at first, then a steady release (75-80%) up to 24 h following the Korsmeyer Peppas release model. In the Isoproterenol induced myocardial necrosis model, oral administration of V-SLNs positively modulated almost all the studied hemodynamic parameters such as left ventricular end-diastolic pressure, cardiac injury markers, and tissue architecture. The cardioprotective effect was also confirmed with histopathological studies. When compared with free drugs, in-vivo pharmacokinetic studies demonstrated a rise in t1/2, AUC0-∞, and Cmax, indicating that bioavailability has improved. These encouraging results demonstrate the promising potential of developed V-SLNs for oral delivery and thereby improve the therapeutic outcome.

Mannosylated nanocarriers mediated site-specific drug delivery for the treatment of cancer and other infectious diseases: A state of the art review.

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.

Targeting pulmonary tuberculosis using nanocarrier-based dry powder inhalation: current status and futuristic need.

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.

Evaluation of Nanocarrier-Based Dry Powder Formulations for Inhalation with Special Reference to Anti-Tuberculosis Drugs.

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.

Innovative strategies in the diagnosis and treatment of tuberculosis: a patent review (2014-2017).

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.

Nanostructured lipid carriers-based drug delivery for treating various lung diseases: A State-of-the-Art Review.

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.

Critical Review on the Analytical Methods for the Estimation of Clofazimine in Bulk, Biological Fluids and Pharmaceutical Formulations.

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.