Estimation of the thermodynamic properties of proteins in mixed solvents is crucial for understanding the effect of cosolvents on rates and equilibrium constants of reactions involving proteins. In this paper, a predictive, molecular level approach for the study of preferential interactions of proteins with either water or cosolvents based on all-atom, statistical mechanical models is used to calculate the preferential interaction coefficient of proteins. Model systems comprised of the cosolvents urea, glycerol, arginine hydrochloride, guanidinium hydrochloride, and glucose with the proteins RNase T1, Hen egg white lysozyme, and alpha-chymotrypsinogen A(alpha-Cgn A) are studied. Trajectories in the range 10-20 ns are analyzed in order to validate this method. From the computational perspective, several key aspects of these simulations are investigated in detail. Protein dynamics and cosolvent dynamics play an important role in the estimation of preferential interaction coefficients, and in determining the length of simulation required to get a reliable estimate of the coefficient. Further, simulation results are found to be sensitive to changes in the cosolvent force field parameters. A comparison of simulated and experimental data is performed for two different force field parameters for glycerol and urea in order to assess the sensitivity of the preferential interaction coefficient to changes in force field parameters. This work highlights the effect of length of simulation, cosolvent force field parameters, and protein structure fluctuations on estimation of the preferential interaction coefficient of proteins in mixed solvents.

Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production.

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Rheumatoid arthritis (RA) is a painful, debilitating disease characterized by inflammation of the joints, with the proliferation of the synovium and the progressive erosion of cartilage and bone. The treatment of RA is still unsatisfactory, but a number of powerful disease-modifying antirheumatic drugs have become available, such as methotrexate (MTX). Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA. The combination of its perceived efficacy, acceptable safety profile, and low cost, as well as decades of clinical experience, makes MTX the cornerstone of treatment for RA and the anchor drug in combination with various biological agents. In this review, the authors aim to summarize the research done in the field of drug delivery systems of MTX according to its routes of administration for treatment of RA. The last part of the review addresses combination therapy with MTX and future direction in the drug delivery of MTX. This review also provides the reader with a general overview of RA and its therapeutic strategies with respect of MTX, which may bring uniformity in medical practice for effective management of RA.

The rationale behind present research effort was to enhance CTZ solubility and efficacyviaforming complex with hydroxypropyl β-cyclodextrin (HP-β-CD) nanosponges.