For the characterization of TNF and its inhibitors we carried out thermodynamic study and generated data were used to set the thermodynamic model with the purpose to understand the molecular forces involved in the recognition of TNF by the antibody with inhibitory activity. We studied the energetics of binding of a therapeutic antibody fragment (Fab) to the native and nonnative forms of TNFα by employing calorimetric and spectroscopic methods. The data were supported by structural modeling. We demonstrated that the observed high affinity binding of Fab to TNFα is an enthalpydriven process due mainly to specific noncovalent interactions.The study results contribute to a better understanding of the molecular mechanism of regulation of TNF activity, which will help us in designing potential inhibitors of TNF based on chemically modified analogues. The study will also assist in the development of biosimilar TNF inhibitors on the basis of mAbs.
COBISS.SI-ID: 35833349
Paper describes detected changes in selected product attributes of three marketed biologics, both from EU and US markets. All changes had been approved by regulatory agencies (i.e. information on the drugs remained unchanged). This is very important achievement, as such changes had been only speculated about so far. Data on more than ten analysed batches of each biologics before and after detected change are presented in the paper. Based on these facts more fair discussion on approval for biosimilar drugs by regulatory agencies it is expected.
COBISS.SI-ID: 1453148
A chapter in a book that combines various methods of extending the half life of proteins. Our chapter deals with PEGylation and describes various aspects achieved by PEGylation. From halflife extension dependent on various PEG shapes and lengths to the proteolytic stability improvement of modified proteins, advantages and potential disadvantages of PEGylation, which are largely related to the potential accumulation of long PEG chains in the body.
COBISS.SI-ID: 1490012
The aim of this study was to develop a sirolimus solid oral dosage form containing a precipitation inhibitor, which would result in an improved sirolimus absorption in humans compared to the formulation containing nanosized sirolimus without a precipitation inhibitor, i.e., Rapamune. The selection of the precipitation inhibitor was based on the results of a screening campaign that identified two “hit” excipients: HPMC 603 (i.e., Pharmacoat 603) and Poloxamer 407. Differential scanning calorimetry (DSC) and an infrared (IR) spectroscopy study revealed that interactions between the sirolimus and HPMC 603 were developed that could lead to the observed precipitation inhibition effect. A human pharmacokinetic study outlined that significantly higher AUC and Cmax were obtained for formulations with HPMC 603coated sirolimus particles in comparison to Rapamune. This result could be attributed to the HPMC 603 (Pharmacoat 603) mediated sirolimus precipitation inhibition resulting in improved sirolimus absorption from the gastrointestinal tract in humans.
COBISS.SI-ID: 1533276
A new PEGylation reagent enabling selective modification of free thiol groups is described in this article. The active group of this new PEGSe reagent is a diselenide, reacting with thiols. The reagent was used for the preparation of PEGylated conjugate of hGCSF with the PEG attachment to the free Cys18. For comparison, conjugates with commercially available reagents PEGMal and PEGOPSS were prepared. Purified monoPEGylated rhGCSF conjugates were characterized and compared. Significant differences in activity, stability, and in vivo performance were observed, although all conjugates contained a 20 kDa PEG attached to the Cys18. The conjugate prepared with PEGSe had the highest in vitro biological activity, while the conjugate prepared with PEGOPSS had the best in vivo performance.
COBISS.SI-ID: 1534556