Navigating the landscape of psoriasis therapy: novel targeted pathways and emerging trends.

INTRODUCTION: Psoriasis is a chronic, inflammatory, non-communicable skin disorder that affects a patient's social and emotional well-being. It is characterized by hyperproliferation of keratinocytes, irregular shedding of skin cells, and abnormal invasion of inflammatory mediators. The treatment strategy is designed based on the severity of the disease condition starting from topical, phototherapy, systemic, and biologics. In recent years, extensive research into the underlying mechanisms of psoriasis has led to significant advancement in treatment options from small molecules to biologics. AREA COVERED: This review focuses on intracellular and molecular mechanisms such as AhR, A3AR, RIP1, CGRP, and S1P that serve as novel pharmacological targets for psoriasis. Moreover, new molecules are approved or are under clinical investigation to interfere with these target mechanisms. EXPERT OPINION: A detailed understanding of signaling pathways provides potential targets and molecular mechanisms for the inflammatory cascade in psoriasis. This has led to the development of small molecules targeting specific pathways. Further, the combination of nanotechnology can assist in dose reduction leading to reduced adverse effects in the management of psoriasis.

Atazanavir-Concentrate Loaded Soft Gelatin Capsule for Enhanced Concentration in Plasma, Brain, Spleen, and Lymphatics.

This study investigates the development of atazanavir-concentrate loaded soft gelatin capsule for achieving enhanced atazanavir (ATV) concentration in plasma, brain, spleen, and lymphatics beneficial in the significant reduction of viral load in HIV infection. For this purpose, ATV-concentrate in the presence and absence of Soluplus with corn oil, oleic acid, tween 80, and propylene glycol was developed. The developed ATV-concentrate was found to have enhanced dispersibility with no signs of precipitation after dilution with simulated G.I fluid as evident from particle size (16.49±0.32 nm) and PDI (0.217±0.02) analysis. The rheological and molecular docking studies explainedthe reduction of viscosity of SuATV-C due to the intermolecular H-bond between ATV and Soluplus that helps to retard crystallization. The shell of the soft gelatin capsule retains its integrity when subjected to a folding endurance test on a texture analyzer depicting that the concentrate did not affect the integrity of the soft gelatin capsule shell. An ex vivo and in vivo pharmacokinetic study in rats revealed that the SuATV-C soft gelatin capsule (SuATV-C SGC) indicated 2.9 fold improvement in rate and extent of permeation and absorption than that of ATV-suspension. The tissue distribution study also exhibited higher drug concentration in the brain (2.5 fold), lymph nodes (2.7 fold), and spleen (1.2 fold) administered with SuATV-C SGC, revealing the overwhelming influence of Soluplus and corn oil. In a nutshell, these studies demonstrated that SuATV-C SGC seems to have the potential to deliver an anti-retroviral drug to the viral sanctuaries for the better management of HIV.

Investigating the potential of Tamarindus indica pectin-chitosan conjugate for reducing recovery period in TNBS induced colitis.

The present study was aimed at exploiting the wound healing applications and tablet coating potential of Tamarindus indica pectin-chitosan (PCH) conjugate for reducing recovery period from TNBS induced colitis. The PCH (60:40, 3% w/v) solution when spray coated followed by drying at 50°C created hydrophobic surface, that may be due to interaction of pectin with chitosan as evident from temperature ramping rheological investigations. Further, the 15% w/v coating was sufficient to prevent Mesalamine (Ma) release in pH 1.2. The AUC and AUMC of PCH coated tablets were 1.98 and 17.69 fold increased as compared to uncoated tablets. A synergistic therapeutic effect of PCH conjugate with Ma was evident from the colon/body weight ratio, clinical activity and damage score. Overall, the findings suggested PCH and Ma (20mg) reduces the recovery period from 5 to 4days with reduction in dose.

Development of aprepitant loaded orally disintegrating films for enhanced pharmacokinetic performance.

The present investigation was aimed to prepare orally disintegrating films (ODFs) containing aprepitant (APT), an antiemetic drug employing pullulan as film forming agent, tamarind pectin as wetting agent and liquid glucose as plasticizer and solubiliser. The ODFs were prepared using solvent casting method. The method was optimized employing 3(2) full factorial design considering proportion of pullulan: tamarind pectin and concentration of liquid glucose as independent variables and disintegration time, wetting time, folding endurance, tensile strength and extensibility as dependent variables. The optimized ODF was evaluated for various physicochemical, mechanical, drug release kinetics and bioavailability studies. The results suggested prepared film has uniform film surface, non-sticky and disintegrated within 18s. The in-vitro release kinetics revealed more than 87% aprepitant was released from optimized ODF as compared to 85%, 49%, and 12% aprepitant release from marketed formulation Aprecap, micronized aprepitant and non micronized aprepitant, respectively. The results of animal preference study indicated that developed aprepitant loaded ODFs are accepted by rabbits as food material. Animal pharmacokinetic (PK) study showed 1.80, 1.56 and 1.36 fold enhancement in relative bioavailability for aprepitant loaded ODF, Aprecap and micronized aprepitant respectively, in comparison with non-micronized aprepitant. Overall, the solubilised aprepitant when incorporated in the form of aprepitant loaded ODF showed enhanced bioavailability as compared to micronized/non-micronized aprepitant based oral formulations. These findings suggested that aprepitant loaded ODF could be effective for antiemesis during cancer chemotherapy.

Physicochemical and functional performance of pectin extracted by QbD approach from Tamarindus indica L. pulp.

The aim of present investigation was to utilize quality by design (QbD) approach for extraction of tamarind pectin (TP) from Tamarindus indica L. pulp employing purity descriptors as indicator. The software generated quadratic equations showed significant effect of polarity index as compared to pulp concentration and boiling temperature on percentage yield and purity characteristics of TP. An insignificant effect on purity descriptors and percentage yield of TP upon replacement of acetone with methanol during predicted vs observed correlation studies (being similar polarity index of 5.1) pointed towards overwhelming influence of solvent polarity. Further, the FTIR-ATR, (1)H NMR, DSC and mass spectroscopy suggested TP was rhamnogalacturonan pectin with no tartaric acid content. TP was found to have significantly higher antioxidant activity as compare to apple pomace pectin, citrus peel pectin and commercial pectin. Overall, the physicochemical properties and antioxidant potential of TP could be utilized as an excipient for food and pharmaceutical industry.

Tamarindus indica pectin blend film composition for coating tablets with enhanced adhesive force strength.

Tablet coating is the most useful method to improve tablet texture, odour and mask taste. Thus, the present investigation was aimed at developing an industrially acceptable aqueous tablet coating material. The physico-chemical, electrical and SEM investigations ensures that blending of Tamarindus indica (Linn.) pectin (TP) with chitosan gives water resistant film texture. Therefore, CH-TP (60:40) spray coated tablets were prepared. The evaluation of CH-TP coated tablets showed enhanced adhesive force strength (between tablet surface to coat) and negligible cohesive force strength (between two tablets) both evaluated using texture analyzer. The comparison of CH-TP coated tablets with Eudragit coated tablets further supported superiority of the former material. Thus, the findings pointed towards the potential of CH-TP for use as a tablet coating material in food as well as pharmaceutical industry.

Aegle marmelos fruit pectin for food and pharmaceuticals: Physico-chemical, rheological and functional performance.

Pectin is used in a number of foods as a gelling agent, thickener, texturizer, emulsifier and stabilizer. Bael fruit, obtained from Aegle marmelos, is a rich source of pectin. Bael fruit pectin (BFP) was extracted from ripe Bael fruits. The process yielded 15% (w/w) pure BFP. The swelling index decreased in the following order: water>pH 7.4>pH 6.8>pH 1.2>HCl (0.1N). Galacturonic acid content of 87.8%, degree of esterification of 47.2%, 17.3% methoxy groups, 0.29% acetyl groups and equivalent weight of 1209.5, indicate it to be a good gelling agent and easily amenable to derivatization. BFP exhibited a significant concentration-dependent prolongation of prothrombin time. The absence of hemagglutinating activity and antinutritional factors coupled with the activity to confer better emulsion capacity, stability and antimicrobial activity gives BFP a clear edge over commercial citrus pectin (CP) for exploitation as an additive in food and pharmaceuticals.

Molecular weight determination and correlation analysis of Dalbergia sissoo polysaccharide with constituent oligosaccharides.

INTRODUCTION: Mucilaginous polysaccharide extracted from Dalbergia sissoo Roxb. leaves has a number of medicinal applications. Molecular weight studies and correlation analysis of the structure of polysaccharide with oligosaccharides can be helpful for further utilisation, modification and structure-activity relationship for biological applications. OBJECTIVE: To determine molecular weight of medicinally important polysaccharide. To establish an unequivocal correlation of the polysaccharide monosugars with constituting oligosaccharides and glucuronic acid content based on gas-liquid chromatography (GLC) with the spectrophotometric method. METHODOLOGY: Complete and partial hydrolytic studies of pure polysaccharide yielded constituting monosugars and oligosaccharides. The ratio of sugars in polysaccharide and oligosaccharides was studied by preparation of alditol acetates and analysed using GLC. The uronic acid content was studied by GLC analysis and spectrophotometry. Molecular weight of the polysaccharide was determined using the viscometric method. RESULTS: Dalbergia sissoo leaves yielded 14.0% pure polysaccharide, containing 15.7% of glucuronic acid. Complete hydrolysis and GLC analysis of alditol acetate derivatives of reduced and unreduced monosugars indicated the presence of L-rhamnose, D-glucuronic acid, D-galactose and D-glucose in 1.00:1.00:2.00:2.33 molar ratios. Partial hydrolysis followed by monosugar analysis of oligosaccharides established the monosugar ratio in complete agreement with polysaccharide, thereby corroborating the sugar ratio. Similar uronic acid content was obtained by GLC and spectrophotometry. The polysaccharide had an average molecular weight of 1.5 × 105 Da. CONCLUSION: The study has established an obvious correlation of the structure of polysaccharide with oligosaccharides, leading to unambiguous identification of monosaccharides, which normally is not studied conclusively while reporting the polysaccharide structure. The molecular weight of the polysaccharide was determined.

Exploiting the synergistic effect of chitosan-EDTA conjugate with MSA for the early recovery from colitis.

The present study was aimed to exploit the antibacterial/antifungal and film coating potential of Chitosan-EDTA (CH-EDTA) conjugate in combination with mesalamine (anti-inflammatory agent) for the early recovery from TNBS induced coilitis. The results suggested CH:EDTA (1:1) spray coated mesalamine tablets has an ability to transport drug in buffer pH 6.8 with rat caecal content condition. The CH-EDTA shows high level of adhesiveness of coat with core tablet. Further, FTIR, DSC and SEM analysis suggested spray coating of CH-EDTA on tablets was beneficial as compared to ladling method as it enhances interaction density and showed resistance from pH (1.2, 6.8 and 7.4). The pharmacokinetic parameters, AUC and AUMC of spray coated tablets were respectively, 4.70 fold and 2.10 fold increased. A synergistic therapeutic effect with CH-EDTA spray coated mesalamine was observed as evaluated by colon/body weight ratio, clinical activity score and damage score. X ray image study supported that CH-EDTA conjugate successfully delivered MSA tablets to large intestine. Histopathology of colon tissues showed rapid recovery from TNBS induced colitis in rats within 4 days. The findings revealed decreased recovery period was due to combined effect of both CH-EDTA and MSA to treat TNBS induced colitis.

An insight into the properties of Aegle marmelos pectin-chitosan cross-linked films.

Pectin of Aegle marmelos (AP) ripe fruits processed in equal proportion with chitosan (CH) formed films that exhibited minimum swelling index and volume index on exposure to buffers of acidic and alkaline pH. Highest contact angle and spreading coefficient coupled with lowest work of adhesion in all buffers for this film suggested availability of limited number of functional groups for interaction with water molecules due to optimum cross-linking between -NH(3)(+) groups of CH and -COO(-) groups of AP. This contention was substantiated by the presence of almost negligible charge on this film. The endothermic transition ΔH characteristic of -NH(3)(+)-COO(-) cross-linking between groups in this film was observed to decrease by only 1% after its sequential exposure to pH 1.2 (3 h) and pH 7.4 (6 h). Furthermore, the absence of pores or erosion in the scanning electron photomicrograph suggested the versatility of this film due to its resistance to acidic and alkaline pH.

Structural characterization of an acidic polysaccharide from Dalbergia sissoo Roxb. leaves.

The composition and structure of an acidic polysaccharide from the leaves of Dalbergia sissoo was studied using hydrolytic, methylation, (1)H/(13)C heteronuclear multiple quantum coherence (HMQC) and periodate oxidation experiments. The repeating unit of sissoo polysaccharide was found to be composed of α-L-rhamnose, ß-D-glucuronic acid, ß-D-galactose and ß-D-glucose in the molar ratio of 1.00:1.00:2.00:2.33, respectively. The structure of polysaccharide was mainly composed of (1→2), (1→3), (1→4) linkages. Based on extensive laboratory experiments, the structure having the repeating units of the acidic polysaccharide from sissoo leaves, with unusual branching, was established.

Immunomodulatory and therapeutic potential of a mycelial lectin from Aspergillus nidulans.

Lectins bind to surface receptors on target cells, and activate a cascade of events, eventually leading to altered immune status of host. The immunomodulatory potential of purified lectin from Aspergillus nidulans was evaluated in Swiss albino mice treated intraperitoneally with seven different doses of purified lectin. Lectin prevented BSA-induced Arthus reaction and systemic anaphylaxis. The enhanced functional ability of macrophages was evident from respiratory burst activity and nitric oxide production in splenocyte cultures. Interferon-gamma and interleukin-6 levels were significantly up-regulated in treated groups. Maximum stimulatory effect was observed at the dose of 1.5 mg/kg body weight. Therapeutic potential of A. nidulans lectin was assessed against trinitrobenzene sulfonic acid-induced ulcerative colitis in male Wistar rats. Rats pre-treated with 80 mg/kg body weight of purified lectin intraperitoneally prior to colitis induction showed lesser disease severity and recovery within 7 days, while rats post-treated with the same dose showed recovery in 11 days. The results demonstrate immunomodulatory effects of A. nidulans lectin in Swiss albino mice, resulting in improved immune status of the animals and unfold its curative effect against ulcerative colitis in rat model. This is the first report on immunomodulatory and therapeutic potential of a lectin from microfungi.

Formulation and evaluation of domperidone loaded mineral oil entrapped emulsion gel (MOEG) buoyant beads.

Alginate based mineral oil entrapped emulsion gel (MOEG) buoyant beads of domperidone were prepared by emulsion gelation technique. The prepared beads were evaluated for particle size, surface morphology, buoyancy, actual drug content and entrapment efficiency. Effect of different oils (castor oil, olive oil and linseed oil) and oil concentrations (10%, 15% and 20%, w/w) on uniformity, homogeneity and integrity of the beads was also studied. Density of the formulated beads was found to be ranging between 0.101 and 0.182 g/cm3. The results of the in vitro drug release indicated that linseed oil showed to be good release retardant compared to castor oil and olive oil. Moreover, the beads formulated using 15%, w/w linseed oil were more uniform in shape, exhibited maximum buoyancy and minimal oil leakage. Diffusion exponent (n) value varied from 0.4855 to 0.7710 indicating anomalous drug release behavior involving swelling, diffusion and/or erosion of the polymer matrix.