Stepanov A.V.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry |
Belogurov A.A.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry |
Mamedov A.E.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry |
Melamed D.,Assaf Harofeh Medical Center |
And 8 more authors.
Russian Journal of Bioorganic Chemistry
Multiple sclerosis (MS) is a severe autoimmune neurodegenerative disease. It attacks mainly young people. The development of new approaches to MS treatment is a challenge to modern immunology and pharmacology. In the present study, a high therapeutic efficacy of immunodominant peptides of myelin basic protein (MBP) incorporated into unilamellar mannosylated liposomes in the development of experi-mental autoimmune encephalomyelitis (EAE) is demonstrated in DA rats. MBP is a component of the oli-godendrocyte membrane, which forms the axonal sheath. This protein is among the major autoantigens in MS. We have analyzed the binding pattern of anti-MBP autoantibodies from MS patients using a previously designed MBP epitope library. Utilizing the same approach, we have investigated the pool of anti-MBP anti-bodies from SJL/J and C57BL/6mice and DA rats with EAE. According to the autoantibody binding pat-terns, the rodent model most closely mimicking MS is EAE in DA rats. We have chosen three immunodom-inant MBP fragments encapsulated in unilamellar mannosylated liposomes for the treatment of the verified DA rodent model. MBP fragment 46-62 is the most efficient in mitigating the first EAE attack, whereas MBP 124-139 and 147-160 inhibit the development of pathology at the regression stage. Simultaneous administration of these peptides in liposomes significantly reduces the level of antibodies against MBP. The synergistic therapeutic effect of MBP fragments reduces the integral disease score by inhibiting the first EAE attack and mitigating the subsequent relapse. Thus, our findings offer new opportunities for the efficient treatment of multiple sclerosis. © Pleiades Publishing, Ltd., 2012. Source
Bode G.H.,Maastricht University |
Pickl K.E.,Joanneum Research |
Sanchez-Purra M.,Ramon Llull University |
Albaiges B.,Ramon Llull University |
And 34 more authors.
Aims: The aim of the current study was to develop a method to detect peptide-linked nanoparticles in blood plasma. Materials & Methods: A convenient enzyme linked immunosorbent assay (ELISA) was developed for the detection of peptides functionalized with biotin and fluorescein groups. As a proof of principle, polymerized pentafluorophenyl methacrylate nanoparticles linked to biotin-carboxyfluorescein labeled peptides were intravenously injected in Wistar rats. Serial blood plasma samples were analyzed by ELISA and by liquid chromatography mass spectrometry (LC/MS) technology. Results: The ELISA based method for the detection of FITC labeled peptides had a detection limit of 1 ng/mL. We were able to accurately measure peptides bound to pentafluorophenyl meth-acrylate nanoparticles in blood plasma of rats, and similar results were obtained by LC/MS. Conclusions: We detected FITC-labeled peptides on pentafluorophenyl methacrylate nanoparticles after injection in vivo. This method can be extended to detect nanoparticles with different chemical compositions. © 2015 Bode et al. Source
Jain S.,Pharmaceutics Research Projects Laboratory |
Jain S.,Lipoxen PLC |
Khare P.,Pharmaceutics Research Projects Laboratory |
Gulbake A.,Pharmaceutics Research Projects Laboratory |
And 2 more authors.
Topical application of the drugs at the pathological sites offers potential advantages of delivering the drug directly to the site of action. The main aim of this work was to formulate and evaluate Miconazole nitrate (MN) loaded solid lipid nanoparticles (SLN) for topical application. MN-loaded SLN were prepared by modified solvent injection method and characterized for shape, surface morphology, particle size, and drug entrapment. These solid lipid nanoparticles were spherical in shape with smooth surface and possessed mean average size of 206.39±9.37nm. In vitro drug release of MN-loaded SLN-bearing hydrogel was compared with MN suspension and MN hydrogel; MN-loaded SLN-bearing hydrogel depicted a sustained drug release over a 24-h period. Tape stripping experiments demonstrated 10-fold greater retention with MN-loaded SLN-bearing hydrogel as compared to MN suspension and MN hydrogel. The in vivo studies were performed by infecting the rats with candida species. It was observed that MN-loaded SLN-bearing hydrogel was more efficient in the treatment of candidiasis. Results indicate that MN-loaded SLN-bearing hydrogel provides a sustaining MN topical effect as well as quicker relief from fungal infection. © 2010 Informa UK Ltd. Source
Zhang R.,Lipoxen PLC |
Jain S.,Lipoxen PLC |
Rowland M.,United Technologies |
Hussain N.,United Technologies |
And 2 more authors.
Journal of Diabetes Science and Technology
Background: The need for lifelong, daily insulin injections can have a dramatic effect on patient compliance, can be painful, and runs the risk of local infections. Furthermore, needle-stick injuries are common, and the issue of needle disposal is troublesome. Injecting a long-acting insulin analog with needle-free administration would be a significant improvement for diabetic subjects, but is not currently feasible. To achieve a constant, reliable delivery of a novel, long-acting insulin analog, Lipoxen's SuliXen® (polysialylated insulin) in a solid dosage form capable of being delivered without a needle has been developed. The aim of this study was to evaluate the feasibility of Lipoxen's SuliXen delivery with the Glide solid dose injector, Glide SDI®. Materials and Methods: A formulation containing 14 kDa polysialic acid (PSA)-recombinant human insulin conjugate was manufactured at Lipoxen PLC and transferred to Glide Pharma. The PSA-insulin conjugate solution was incorporated into different excipients at Glide Pharma (excipients 1 and 2), and formulations were manufactured containing implants with doses of 0.3 and 1.0 IU of insulin, respectively. Two different polymeric excipients were investigated for their suitable release profiles. The physicomechanical properties of the formulations were characterized in terms of solid dosage form strength (via three-point bend and compression) and disintegration time at 37°C. A preclinical efficacy study was performed in a nondiabetic rat model (Sprague-Dawley). Results: The study demonstrated successful incorporation of PSA-insulin conjugate into formulations compatible for use with the solid dose injector. Physicochemical characterization indicated that each formulation produced was physically robust. For excipient 1, the compressive stress and three-point-bend-test values recorded for the 0.3 IU formulation were 106.99 ± 14.3 MPa and 30.6 ± 1.4 N (force in newtons), respectively. Corresponding values for the 1.0 IU dose were 53.10 ± 10.2 MPa and 16.66 ± 1.0 N. For excipient 2, the compressive stress and three-point-bend- test values recorded for the 0.3 IU dose were 53.10 ± 10.2 MPa and 7.64 ± 0.9 N, respectively, whereas the corresponding values recorded for the 1.0 IU dose were 41.61 ± 7.4 MPa and 13.18 ± 1.3 N. Each formulation successfully penetrated a laboratory substrate, achieving 100% penetration in each case. In vivo analysis demonstrated that PSA-insulin conjugate shows prolongation of activity (at least two-fold more compared to insulin) for more than 5 hours in the rat model. Conclusion: Even though additional work may be required, for example, to develop several fixed dose formulations, the preliminary results show that solid dosage forms incorporating PSA-insulin conjugate maintained the prolongation of PSA-insulin conjugate activity in the rat model. Convenient and easy to use, the solid dose injector will not only ensure diabetic patient compliance and trust but also provide cost-effective solutions for safe, reliable, and controlled needle-free injection of PSA-insulin conjugate. © Diabetes Technology Society. Source