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Ulcerative colitis (UC) is an idiopathic, chronic and relapsing colonic inflammatory disease. Despite the involvement of diverse intricate mechanisms, COX mediated inflammatory pathway is crucial in the pathophysiology of colitis. Thus, COX inhibition is imperative for managing colitis-associated inflammation. However, the use of COX inhibitory classical non-steroidal anti-inflammatory drugs (NSAIDs) for inflammation resolution has been linked to sudden increased flare-ups. Therefore, considering the anti-inflammatory and pro-resolution effects of antioxidant and essential trace element Selenium (Se), a Seleno-derivative of Celecoxib called Selenocoxib-3 was characterized and evaluated for its favourable pharmacokinetics, safety margins and anti-inflammatory therapeutic potential in DSS-induced experimental colitis. The serum pharmacokinetic profiling [elimination rate constant (K) and clearance (Cl) and toxicity profiling suggested enhanced efficacy, therapeutic potential and lesser toxicity of Selenocoxib-3 as compared to its parent NSAID Celecoxib. In vivo studies demonstrated that Selenocoxib-3 efficiently resolves the gross morphological signs of DSS-induced colitis such as diarrhoea, bloody stools, weight loss and colon shortening. Further, intestinal damage evaluated by HE staining and MPO activity suggested of histopathological disruptions, such as neutrophil infiltration, mucodepletion and cryptitis, by Selenocoxib-3. The expression profiles of COX-1/2 demonstrated mitigation of pro-inflammatory mediators thereby promoting anti-inflammatory efficacy of Selenocoxib-3 when compared with Celecoxib. The current study suggests translational applicability of Se-containing novel class of COX inhibitors for efficiently managing inflammatory disorders such as UC.

A novel fabrication of magnetite (Fe

The present study aimed to develop topical combinatorial therapy of nisin and 5-fluorouracil in a single nanosized formulation against skin cancer.Nisin and 5-fluorouracil were encapsulated in an organogel system (NF-OG) and investigated for morphology, physicochemical properties, cytotoxicity, encapsulation and release. NF-OG was evaluated against DMBA/TPA murine skin cancer in terms of tumour statistics, histoarchitecture, TUNEL and M1/M2 macrophages.The optimised NF-OG formulation exhibited particle size of 185.1 ± 11.24 nm, zeta potential of -7.93 ± 0.60 mV, offered substantial drug loading and temporal release. NF-OG therapy led to improved cytotoxicity of nisin and 5-FU against B16-F10 cells, significant decrease in tumour volume (84.983 mmThe study yielded a promising delivery system exhibiting potent anticancer activity and forms the bases for further applications in clinical settings.

In modern world, Pharma sector observes steep increase in demand of personalized medicine. Various unique ideas and technology were proposed and implemented by different researchers to prepare personalized medicine and devices. 3-dimensional printing (3DP) is one of the revolutionary technologies which can be used to prepare tailored medicine via CAD (Computer Aided Design) software. 3DP allows researchers to manufacture customized dosage form with desired modifications in geometry which would in turn alter dosage behaviour of the product with reduced side effects. Current achievement of 3DP includes personalized and adjustable dosage form, multifunction drug delivery systems, medical devices, phantoms, and implants specific to patient anatomy. Additionally, 3DP is employed for preparing tailored regenerative medicines. This review focuses on 3DP use in pharmaceuticals including drug delivery systems and medical devices with their method of fabrication. Additionally, different clinical trials as well as different patents done till date are cited in the paper. Furthermore, regulatory issues and future perspective related to 3 D printing is also well discussed.

The combination therapy of Isotretinoin (ITR) and antibacterial formulations administered through topical route suffer from several limitations including reduced therapeutic efficacy and low patient-compliance.The present study aimed to develop biocompatible lipid-based mixed micelles of ITR in combination with Clindamycin phosphate (CLIN) employing self-assembly method to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy.The MTT assay and cellular uptake studies showed non-cytotoxic effect to HaCat cell lines. The zone of inhibition studies conducted inThe lab developed lipid-based micellar formulation of ITR and CLIN offers a better strategy for the combined delivery of unstable molecules like ITR and CLIN in acne management.

Since the discovery of liposomes, these vesicular carriers have attracted the researchers from all the vistas of the biomedical domain to explore and harness the potential benefits. Many novel drug delivery-based products have been approved by the United States Food and Drug Administration (USFDA) and other federal agencies of the globe, out of which the major share is of the liposomes and related carriers. Taking cognizance of it, the US-FDA has recently come up with ‘Guidance for Industry on Liposome Drug Products’. In cancer management, chemotherapy is the most frequently employed approach which is still not devoid of untoward challenges and side effects. In chemotherapy, the taxanes, esp. Docetaxel shares a huge percentage in the prescription pattern. Also, the first marketed liposomal product was encasing one drug of this category. Henceforth, the present review will highlight the advances in the delivery of taxanes, in particular docetaxel, with an emphasis on the need, success and pharmacoeconomic aspects of such vesicular-carrier mediated docetaxel delivery.

Many attempts have been made to the refinement of liposomal stability. In 1986, Payne et al. developed the approach of proliposomes to derelict the physicochemical instability confronted in some liposome suspensions, i.e., fusion, aggregation, hydrolysis, and oxidation. This review attempts to cover different aspects of proliposomes along with their types and preparation methods. The review is also focused on the scope of proliposomes as a nano-based drug delivery system and subsequent applications. An attempt has been made to cover all the facets of proliposomes, from their composition to clinical trials. The extensive scientific data from proliposomes provide substantial shreds of evidence for its huge delivery potential.

Owing to the advancements in nanotechnology, there is effective localization of active payloads in the form of self-assembled nanocarriers, which attracted the interest of the researchers. Several literature reports mentioned that nanocarrier-based drug delivery approaches such as self-assembled delivery systems provide higher efficacy with minimal side effects. The clustering of atoms or molecules forms these self-assembled nanosystems with different interaction types such as hydrogen bonding, electrostatic, hydrophobic, and van der Waal interactions. Some of these systems include surfactant-based, polymer-based nanoparticles, polymersomes, pluronic lecithin organogels, mixed self-assemblies, and phospholipid-based self-assemblies. These nanosystems are employed in delivering the drug payloads to the target site, along with some biomedical applications like regenerative biology, tissue engineering, and vaccines. Thus it is expected that the next generation self-assembled supramolecular systems could improve human healthcare with the latest technologies and significant clinical outcomes. This chapter emphasizes various techniques used for the fabrication of self-assembled nanocarriers, their classification and clinical applications. This also focuses on the chemistry behind the formation of supramolecular structure and their enhancing role in biomedical applications.

Sialyl-Lewis-X (sLeX/CD15s) epitopes regulate cell adhesionviainteractions with selectins. High levels of sLeX are associated with chronic inflammation. Intense efforts have been devoted for the development of sLeX mimetics for the prevention of atherosclerosis. By contrast, low levels of sLeX are associated with leukocyte adhesion deficiency (LAD) disorders. In this context, we employed metabolic glycan engineering to alter the fine structures of sialoglycans. Treatment of HL-60 (human acute myeloid leukemia) cells with peracetylN-cyclobutanoyl-D-mannosamine (Ac4ManNCb) resulted in a four-fold increase in both sLeX levels and adhesion to E-selectin-Fc chimera. Enhanced sLeX levels on CD162/PSGL-1, CD43, and CD44 were observed through immunoprecipitation. Molecular dynamics (MD) simulations on interactions with E-selectin revealed dramatic differentials in the conformational dynamics of sLeX-Cb compared to sLeX, highlighting the significance of remoteN-acyl side chains of sialic acids in facilitating bio-active conformations. These results provide opportunities for pharmacological interventions in both LAD and chronic inflammation.Table of ContentsRemote substituents on the tetrasaccharide sialyl-Lewis X (sLeX / CD15s) influence ensembles of bio-active conformations and alter biological outcomes. Treatment with peracetylN-cyclobutanoyl-D-mannosamine (Ac4ManNCb) results in four-fold enhancement in the expression of sialyl-Lewis-X (sLeX / CD15s) and adhesion to E-selectin (CD62E). Molecular dynamics simulations show that the sLeX-Cb prefers a flatter bio-active conformation (gray) compared to wild-type sLeX (cyan).Institute and/or researcher Twitter usernames: @NImmunology @Gops_GlycoIndia

We investigated two ways for fabricating 1, 3, 4, 6-tetra

The current study investigates the potential for topical delivery of a fluticasone propionate (FP) and levocetirizine dihydrochloride (CTZ)-loaded microemulsion (ME) for the management of atopic dermatitis. Various microemulsion components were chosen based on their solubility and emulsification capabilities, and the ternary phase diagram was constructed. A total of 12 microemulsion formulations were screened for various attributes like vesicle size, polydispersity index, ζ-potential, percent transmittance, density, and pH. The average globule size and ζ-potential of FP and levocetirizine-containing ME were 52.12 nm and -2.98 ζ-potential, respectively. Transmission electron microscopy confirmed the spherical nature of the globules. The developed system not only controlled the release of both drugs but also enhanced the efficacy of the drugs on a rodent model. Histopathological studies confirmed the safety of the developed system. The present findings provide evidence for a scalable and simpler approach for the management of atopic dermatitis.

Sorafenib tosylate (SFB) is a multikinase inhibitor that inhibits tumour growth and proliferation for the management of breast cancer but is also associated with issues like toxicity and drug resistance. Also, being a biopharmaceutical class II (BCS II) drug, its oral bioavailability is the other challenge. Henceforth, this report intended to encapsulate SFB into a biocompatible carrier with biodegradable components, i.e., phospholipid. The microemulsion of the SFB was prepared and characterized for the surface charge, morphology, micromeritics and drug release studies. The cell viability assay was performed on 4T1 cell lines and inferred that the IC50 value of sorafenib-loaded microemulsion (SFB-loaded ME) was enhanced compared to the naïve SFB at the concentrations of about 0.75 µM. More drug was available for the pharmacological response, as the protein binding was notably decreased, and the drug from the developed carriers was released in a controlled manner. Furthermore, the pharmacokinetic studies established that the developed nanocarrier was suitable for the oral administration of a drug by substantially enhancing the bioavailability of the drug to that of the free SFB. The results bring forth the preliminary evidence for the future scope of SFB as a successful therapeutic entity in its nano-form for effective and safer cancer chemotherapy via the oral route.

Nanostructured drug delivery formulations have lately gained enormous attention, contributing to their systematic development. Issuance of quality by design (QbD) guidelines by ICH, FDA, and other federal agencies, in this regard, has notably influenced the overall development of drug products, enabling holistic product and process understanding. Owing to the applicability of QbD paradigms, a science lately christened as formulation by design (FbD) has been dedicated exclusively to QbD-enabled drug product development. Consisting of the principal elements of design of experiments (DoE), quality risk management (QRM), and QbD-enabled product comprehension as the fundamental tools in the implementation of FbD, a variety of drug nanocargos have been successfully developed with FbD paradigms and reported in the literature. FbD aims to produce novel and advanced systems utilizing nominal resources of development time, work effort, and money. A systematic FbD approach envisions the entire developmental path through pivotal milestones of risk assessment, factor screening and optimization (both using appropriate experimental designs), multivariate statistical and optimum search tools, along with response surface modeling, usually employing suitable computer software. The design space is one of the fundamental elements of FbD providing the most sought-after regulatory flexibility to pharma companies, postapproval. The present paper provides a bird's eye view of the fundamental aspects of FbD terminology, methodology, and applications in the development of a wide range of nanocargos, as well as a discussion of trends from both technological and regulatory perspectives.

The potential of Dunaliella salina isolated from Sambhar Salt Lake (Rajasthan, India) for biosorption of hexavalent chromium Cr(VI) in aqueous solution has been examined under optimized culture conditions. The influence of various process parameters, such as pH (6–11), incubation time (48–120 h), metal concentration (5–25 mgL-1), inoculum dose (2–10% vv−1), and their combination effects during Cr(VI) sorbtion were analyzed by means of Response Surface Methodology (RSM) based on a 3-level Box-Behnken experiment design. Microalgae showed highest chromium biosorption with 66.4% efficiency at optimum pH (8.6) and 10% (vv−1) inoculum size within 120 h. The experimental data obtained were analyzed by analysis of variance (ANOVA) along with lower value of coefficient of variation (34%), indicated the well fitness of quadratic equation as proposed by response surface model. Involvement of the surface morphology of the microalgae biomass and elemental distribution was studied through Scanning Electron Microscope (SEM), Energy Dispersive X-ray Spectroscopic (EDS), Fourier-transform infrared spectroscopy (FTIR) and X-ray Diffraction (XRD) analysis. The findings unequivocally corroborates that the novel microalgae inherits immense potential in alleviating the levels of toxic heavy metal, such as Cr(VI) from the hydrosphere at wide range of pH and metal concentrations. The present study provides a workable solution for bioremediation of hazardous heavy metals, in general, and Cr(VI) in specific from the industrial wastes like tannery effluents.

Thymoquinone (TQ), a potent bioactive of Nigella sativa plant, is highly hydrophobic molecule and thus associated with poor oral bioavailability. The present work proposes the phospholipid-nanoparticles (PLN) based delivery of TQ to enhance the low oral bioavailability and anti-inflammatory activity. TQ-loaded nanoparticles were prepared via micro-emulsification technique employing different phospholipid concentrations and extensively characterized for particle size, surface charge, surface morphology, entrapment efficiency, and drug release kinetics. Further, the nanoparticles were assessed for oral bioavailability, and anti-inflammatory activity employing rat paw edema model. The optimized nanoparticle composition (F1) was nanosized ( 70%), controlled drug release pattern, and negatively charged surface (zeta potential of −0.57 mV). After oral administration of a single dose of F1 formulation, showed approx. 226.6% relative bioavailability vis-a-vis plain TQ suspension. While, substantially higher reduction in the percent inhibition in paw edema in comparison to the pure drug suspension and diclofenac sodium, was observed in the inflammation model. The present work indicate that PLN could be an efficient nanodevices for the treatment of inflammatory disorders and promising carrier system to augment TQ oral bioavailability.

Ibuprofen, a frequently prescribed nonsteroidal anti-inflammatory drug, is a common environmental pollutant, and its increasing concentration in the environment leads to serious impacts. This concern has demanded a holistic scientific approach for the removal of pharmaceuticals and their by-products from the environment. Microbial degradation is an eco-friendly technique known to degrade complex molecules to simpler forms. The present study focuses on isolating the most potential bacterial strain from pharmaceutical industry site and investigates the biodegradation of ibuprofen. Among six isolated strains, one isolate KGP04 was identified as Micrococcus yunnanensis (GenBank: MG 493238), which exhibited the highest potential to degrade (~ 41.57%) ibuprofen before optimization. Taguchi-based L8 orthogonal array was used to optimize process parameters which improved the degradation rate by 83.50%. Drug concentration was reduced by 90.37% at optimum conditions (carbon 0.15%, nitrogen 0.1%, pH 7, inoculum size 2% (w/v), rpm 150, 12 h, 25 °C), as revealed by high-performance liquid chromatography. Q-time of flight mass spectrometry demonstrated the ibuprofen degradation pathway followed by the strain resulting in various transformative products. Further, the effect of ibuprofen on human embryonic kidney 293 cells was also analyzed through the Alamar Blue assay, which exhibited lower toxicity on the cells treated with the degraded samples. These results indicate that the strain is a capable candidate for the degradation of pharmaceuticals and optimized conditions can be employed to remove the nonsteroidal anti-inflammatory drugs and similar agents in a greener and economic manner from the pharmaceutical effluents.

Due to changed lifestyle and other reasons, diabetes has become one of the common metabolic disorder of the globe. Numerous therapeutic options are available, which controls the plasma glucose levels. However, most of the drugs are associated with some undesired side effects. Owing to the side effects and enhanced understanding of the phytochemicals, an inclination toward herbal medicine is seen in the population. These herbal products are also associated with concerns like poor aqueous solubility, compromised permeation, and a low degree of bioavailability. So, the emergence of nanotechnology in the herbal medicine is required to nullify the associated concerns of conventional antidiabetic drugs. The present review aims to compile the literature available for the nano-interventions pertinent to herbal products for diabetes management.

Breast cancer is one of the leading types among the common non-cutaneous malignancies in women. All the curative methods available for its treatment are minimal due to their toxicity issues and dose-related side effects. Various evolving nanotechnology techniques displayed the opportunity to target breast cancer. One such delivery system is lipid-based drug delivery systems (LDDS). This concept is constrained only for the laboratory scale should be shifted to the industrial level targeting the nanomedicine with clinical benefits. This work tried to portray the advancements in the LDDS along with the lipid-based excipients, advantages, disadvantages and applications. It even helped in highlighting the recently developed lipid-based nanocarriers for breast cancer management.

The emergence of multidrug resistant strains of Pseudomonas aeruginosa necessitates the exploration of novel therapeutic intervention (s). The present study aimed to develop a nisin loaded carbopol gel formulation (NLCG) and explore its therapeutic efficacy against P. aeruginosa infected burn wounds. The formulation was prepared using Carbopol 940 as a polymer and characterized in terms of its appearance, stability, pH, rheology, spreadability, release, and permeation profiles. Disc diffusion assay and field emission scanning electron microscopy were carried out to establish in vitro antibacterial activity while the in vitro cytotoxicity was evaluated by hemolytic and trypan blue exclusion assay. Furthermore, in vivo efficacy was investigated by developing P. aeruginosa infected third-degree murine burn wound model followed by evaluation of parameters like bacterial loads, skin restoration, histopathological architecture, levels of hydroxyproline, myeloperoxidase and cytokines. Our studies yielded a stable formulation with pH, viscosity and drug release flux values as 6.5 ± 0.02, 382.4 p and 160.55 ± 3.64 μg h-1 cm-2 , respectively. Approximately, 84.02 ± 1.63% of nisin was found to permeate into murine skin, further, affirmed by confocal microscopic observations. Interestingly, no in vitro cytotoxicity of NLCG (to erythrocytes and/or to peritoneal macrophages) could be observed. The log units decrease (s) in CFUs of Pseudomonas in skin were found to be 1.5137, 4.2257, 6.456 after 12, 24 and 72 h of topical gel therapy, respectively. Percentage wound closure, tensile strength, histological, and scanning electron microscopic studies further provided a healing evidence with skin showing restoration of the epithelium. The gel therapy also led to a significant modulation (p ≤ 0.05) in hydroxyproline content, myeloperoxidase levels, and serum levels of IL-1, IL-10, and TNF-α. Our formulation revealed anti-Pseudomonas, wound healing, and immunomodulatory efficacy of NLCG. Further investigations are warranted to determine the underlying mechanism (s) of these displayed antibacterial and immunomodulatory effects.

In the present study, water-soluble lysine-based C

The systematic development of pharmaceutical products using quality tools is highly essential for attaining robust performance by minimizing variability. Design of experiment (DoE) is now considered as an indispensable tool in pharmaceutical development to obtain quality products. Among a variety of dosage forms, the topical dosage forms are useful for providing a localized therapeutic effect of the drugs. Such dosage forms include liposomes, ethosomes, niosomes, transfersomes, and many more, where the manufacturing of such dosage forms includes multifunctional excipients and a number of unit operations. Hence, the use of DoE provides greater flexibility and is highly effective for the efficient development of topical products with ultimate savings of the resources. The present chapter, therefore, provides a holistic account on the implementation of DoE approach for the manufacturing of topical drug products and also highlights the current challenges and opportunities associated with them.

Autoimmune diseases fall under the chronic and fatal group of diseases that are generally associated with functional disability and multiple organ failure. These diseases include multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel disease, type 1 diabetes, and psoriasis, which are characterized by multifactorial etiologies, involvement of T-cell-mediated autoimmune pathogenesis, and life-long disease management. These diseases are a complex interplay between genetics, environmental exposure, immune function, and contribute significantly to global morbidity and mortality. Despite significant advancements in targeted therapy, long-term dosing and inadequate targeting options often lead to suboptimal effects in the treatment of autoimmune diseases. A number of studies in the past have reported that autoimmune diseases can be caused by the deregulation of the apoptotic process. Apoptosis is a physiological mechanism of cell death and defects in this cell death pathway lead to the development of autoimmune diseases. With further research into the apoptotic mechanisms, there has been an upsurge of innovative treatment strategies that allow intervention in the apoptotic process for autoimmune diseases. The present article intends to provide an insight of the basis of autoimmune diseases, epidemiology, and their pathophysiology. The manuscript deals with the existing and innovative drug molecules employed in targeting apoptosis for autoimmune disease management. The paper will also focus on nanotechnology-based delivery strategies of these drug molecules.