Gut-Brain Axis and Neurological Disorders-How Microbiomes Affect our Mental Health.

The gut microbiota is an essential part of the gastrointestinal tract and recent research, including clinical and preclinical studies, shed light on the interaction between the gut and the brain. A rising amount of evidence strongly proves the involvement of gut microbes in brain function and their contribution in altering behavior, mood, and ultimately in the pathogenesis of certain neurological conditions. The gut microbiota produces and modulates neurotransmitters such as GABA, serotonin, dopamine, glutamate, etc. Furthermore, there is a presence of a biological link between the microbiota, immune signaling, and CNS suggesting that microbial metabolites could regulate both neurological and immunological activities in the brain. Thus, this review focuses on the bidirectional communication between the gut and brain, its impact and role in the modulation of various neurological disorders, such as schizophrenia, depression, anxiety, etc., and attempts to explore the underlying mechanism for the same. The article also discusses studies involving germ-free mice, studies on the effects of faeces transfer of microbiota, and research involving gut microbiota composition in animal models. The effects of probiotics and prebiotics on neurological disorders are also discussed, along with the clinical studies for each of them. In a nutshell, extensive studies are required to explore this bidirectional communication between the gut and brain, which might help researchers develop new therapeutic targets in treating neurological disorders and increase our understanding of the gut-brain axis.

Cellulose nanocrystals: Fundamentals and biomedical applications.

The present review explores the recent developments of cellulose nanocrystals, a class of captivating nanomaterials in variety of applications. CNCs are made by acid hydrolysing cellulosic materials like wood, cotton, tunicate, flax fibers by sonochemistry. It has many desirable properties, including a high tensile strength, wide surface area, stiffness, exceptional colloidal stability, and the ability to be modified. CNCs are colloidally stable, hydrophilic, and rigid rod-shaped bio-based nanomaterials in the form of rigid rods with high strength and surface area that has a diverse set of applications and properties. The intriguing features emerging from numerous fibers studies, such as renewable character and biodegradability, piqued the curiosity of many researchers who worked on lowering the size of these fibers. Physicochemical properties such as rheological, mechanical, thermal, lipid crystalline, swelling capacity, microstructural properties result in affecting surface-area to volume ratio and crystallinity of cellulose nanocrystals. The present article highlights the fundamentals of cellulose nanocrystals such as sources, isolation, fabrication, properties and surface modification with an emphasis on plethora of biomedical applications. Selected nanocellulose studies with significant findings on cellular labelling and bioimaging, tissue engineering, biosensors, gene delivery, anti-viral property, anti-bacterial property, ocular delivery, modified drug release, anti-cancer activity and enzyme immobilization are emphasized.

Nano intervention in topical delivery of corticosteroid for psoriasis and atopic dermatitis-a systematic review.

Atopic dermatitis (AD) and psoriasis are highly prevalent, complex, chronic inflammatory skin diseases that immensly affect the patient's quality of life. While there is no definitive cure for these conditions, suppressive medications aim at managing the symptoms of these diseases. The application of emollients accompanied by symptomatic anti-inflammatory therapy consisting of topical corticosteroids (TCS) is extensively employed for controlling the symptoms among general practitioners making this therapeutic class an indispensable pillar of dermatotherapeutics. The first TCS, hydrocortisone (HC) introduced in the early 1950s led to the development of different steroidal moieties of varying potencies by inducing chemical modifications to the basic steroid structure. The wide spectrum of the available range of formulations and potency provides flexibility to treat all patient groups, different phases of the diseases, and different anatomical sites. Conventional TCS therapy suffers from drawbacks such as low drug permeation and retention rate. Thus, novel nanoformulations have been developed to overcome these problems. This review provides an insight into the current state of nanocarrier-mediated topical delivery of corticosteroids monotherapy and combination therapy with special emphasis on targeting psoriasis and AD.

Current insights on clinical efficacy of roflumilast for treatment of COPD, asthma and ACOS.

Phosphodiesterase-4 inhibitors (PDE4) are of great interest for the treatment of airway inflammatory diseases due to its broad anti-inflammatory effects. Roflumilast is a selective PDE4 inhibitor that inhibits pulmonary and systemic inflammation and rallies symptoms in airway diseases. Asthma and COPD are common chronic airway inflammatory diseases having incompletely illustrious pathophysiology and clinical manifestations. Recently, the condition called Asthma- COPD Overlap (ACO) has been evolved having the overlapping symptoms of both diseases. The newly discovered PDE4 inhibitor, roflumilast has exposed its potential in the treatment of Asthma, COPD and ACOS. Its mechanism of action in airway inflammatory diseases are said to be exerts by elevating intracellular cAMP and shows its anti-inflammatory action. Roflumilast, a promising therapeutic approach in inflammatory airway diseases, has many significant outcomes. In this review, we have provided various promising clinical evidences of roflumilast in COPD and asthma. However, there is no published clinical evidence to date for the role of roflumilast in ACOS. Nevertheless, there are therapeutic mechanisms that provide a reference for clinical application for ACOS.

CDI cross-linked ß-cyclodextrin nanosponges of paliperidone: synthesis and physicochemical characterization.

Paliperidone (PLP) is an antipsychotic drug indicated for treatment and management of schizophrenia. The current study demonstrates potential of PLP-loaded ß-cyclodextrin-based nanosponges (CDNS) for solubility enhancement and prolonged release of PLP. The inclusion complexes of PLP with carbonyldiimidazole (CDI) cross-linked nanosponges were synthesized. The drug-loaded CDNS were characterized for particle size, zeta potential, encapsulation efficiency, stability study, in vitro drug release studies. The interaction of PLP with CDNS was ascertained by FTIR, DSC and PXRD studies. The particle size and zeta potential values were sufficient to obtain stable formulations. Solubility was significantly increased and in vitro drug release studies revealed prolonged release of PLP from the CDNS for 6 h. PXRD study revealed that the crystallinity of PLP was decreased due to complexation with the CDNS. Thus, cyclodextrin-based nanosponges represent a novel approach for solubility enhancement and improved dissolution of selected model drug PLP.

Design and Development of Novel 2-(Morpholinyl)-N-substituted Phenylquinazolin-4-amines as Selective COX-II Inhibitor.

BACKGROUND: A novel series of 2-(Morpholin-4-yl)-N-phenylquinazolin-4- amine derivatives were synthesized and confirmed with spectral and elemental techniques. METHODS: The compounds were tested for analgesic and anti-inflammatory activity by various pain models in rodents whereas the selectivity towards COX-2 receptor is determined by in vitro assay. RESULTS: Screening results of compounds exhibited comparable biological activity with that of standard compound Indomethacin used for study. Compound 5d was found to be significantly potent with respect to its anti-inflammatory and analgesic activity with substantial COX-II selectivity. CONCLUSION: In silico analysis by molecular docking and 3D-QSAR studies justifies activity profile of compound 5d, suggesting that it may have potential for further evaluation and development as lead molecule for therapy in pain management.

ß-Cyclodextrin-based inclusion complexes and nanocomposites of rivaroxaban for solubility enhancement.

Rivaroxaban (RIV) is an oral anticoagulant used in the prevention of venous thromboembolism in adult patients after total hip replacement or total knee replacement surgery. It is practically insoluble in water and buffer systems (pH 3-9). The present study was aimed to investigate the ß-CD-based inclusion complexes and nanocomposites of rivaroxaban (RIV) for solubility and dissolution enhancement. A novel solubility enhancement approach of inclusion complexation of RIV with ß-CD using spray drying method combined with high pressure homogenization as a particle engineering method was used. Change in crystallinity of RIV nanocomposites was assessed by DSC and PXRD. The interaction of drug with ß-CD was projected through 1H-NMR and FT-IR studies. Saturation solubility and in vitro dissolution study revealed a dramatic increase in solubility and dissolution of RIV, respectively. Thus, spray-dried ß-CD-based nanocomposites could be an innovative approach for solubility and dissolution enhancement of RIV.

Dendrimers: A versatile nanocarrier for drug delivery and targeting.

Dendrimers are novel polymeric nanoarchitectures characterized by hyper-branched 3D-structure having multiple functional groups on the surface that increases their functionality and make them versatile and biocompatible. Their unique properties like nanoscale uniform size, high degree of branching, polyvalency, water solubility, available internal cavities and convenient synthesis approaches make them promising agent for biological and drug delivery applications. Dendrimers have received an enormous attention from researchers among various nanomaterials. Dendrimers can be used as a carrier for diverse therapeutic agents. They can be used for reducing drug toxicities and enhancement of their efficacies. The present review provide a comprehensive outline of synthesis of dendrimers, interaction of dendrimer with guest molecules, properties, characterization and their potential applications in pharmaceutical and biomedical field.

Development and Evaluation of pH-Responsive Cyclodextrin-Based in situ Gel of Paliperidone for Intranasal Delivery.

Paliperidone (PLPD) is approved for treatment and management of schizophrenia. The current study demonstrates the potential of in situ gel of PLPD for nasal delivery. The permeation of drug through sheep nasal mucosa was analyzed since the nose-to-brain pathway has been indicated for delivering drugs to the brain. The carbopol 934 (CP)- and hydroxypropyl methyl cellulose K4M (HPMC)-based in situ gels containing 0.2% CP and 0.4% w/v HPMC were optimized using experimental design software. The use of hydroxypropyl-ß-cyclodextrin (HP-ß-CD) in nasal permeation of drug was investigated. Transmucosal permeation of PLPD was examined using sheep nasal mucosa. The in situ gels of PLPD exhibited satisfactory mucoadhesion and showed sustained drug release. The mucocilliary toxicity and histopathological examination confirmed that the nasal mucosa architecture remains unaffected after treatment with PLPD in situ gel. The formulation containing HP-ß-CD complex of PLPD exhibited higher rate of drug permeation through sheep nasal mucosa revealing the role of HP-ß-CD as nasal absorption enhancer. Thus, CP- and HPMC-based pH-triggered in situ gel containing HP-ß-CD-drug inclusion complex demonstrates a novel nasal delivery of PLPD.

Cyclodextrin-based nanosponges: A critical review.

Cyclodextrin-based nanosponges (CD-NS) are innovative cross-linked cyclodextrin polymers nanostructured within three-dimensional network. CD-NS are highly porous nanoparticles characterized by crystalline or amorphous structure, spherical shape and swelling properties. Different cross-linkers provide variety of nanosponges. The polarity, dimension of the polymer mesh and release of entrapped molecule can be easily tuned by varying the type of cross-linker and degree of cross-linking. The site-specific targeting can be achieved by conjugating various ligands on the surface of nanosponge. They offer unique advantage of controlled release and are biologically safe and biodegradable material. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances and as innovative carrier in pharmaceuticals, cosmetics, protein/peptide delivery, diagnostics, enzyme-catalysed reactions, environmental control and agrochemistry.

Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies.

The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and to study the effect of l-arginine (l-Arg) as an auxiliary agent on the complexation efficiency of HP-ß-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through 1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, l-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-ß-CD was observed in the presence of l-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with l-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-ß-CD-l-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD.