Solubilization of rifapentine with human serum albumin (HSA) was used to produce a water-miscible form consisting of a colloidal suspension of particles of size 538 ± 9 nm. Dilution of the suspension more than 20-fold led to dissociation of the aggregates formed during solubilization procedure, producing a transparent solution. This was associated with a reduction in particle size to 10 – 20 nm, corresponding to the particle size in HSA solution at the same concentration. A fluorescence method showed that suspensions contained both free rifapentine and its complex with HSA. Studies of the activity against the pathogen of tuberculosis, Mycobacterium tuberculosis H37Rv, in a model of acute infection in Balb/c mice showed that the water-miscible form of rifapentine given intravenously had high activity against mycobacteria, comparable with the activity of rifapentine substance, decreasing mycobacterial loadings in the parenchymatous organs from 106 – 107 to 102 – 103 cfu/organ. Thus, use of HSA as solubilizer yielded an intravenous form of rifapentine retaining the activity of the antibiotic against Mycobacterium tuberculosis.

Parenteral formulations of the poorly soluble antituberculosis antibiotic rifapentine were developed. Proteins (human serum albumin, succinylated gelatin, and sodium caseinate) were used to produce water-soluble forms of rifapentine by precipitation or homogenization. Ultrasonic homogenization gave the best results, i.e., stable colloidal suspensions with 9 – 10 mg of rifapentine per mL (practically 100 times greater than its water solubility). Dilution of the suspensions led to dissociation of the aggregates formed during the solubilization and formation of a clear solution. The particle size decreased to 10 – 20 nm, which corresponded to the particle size in a solution of the proteins at the same concentration. This would not cause embolization upon infusion of such water-soluble forms of rifapentine. The results indicated that the selected approach was promising for designing parenteral formulations of rifapentine.

The aim of the present work was to develop methods for the preparation of a nanosomal form of low-sialylated recombinant human erythropoietin (ls-rhEPO), which has neurotropic antihemorrhagic activity. Measurements were made of the sorption of erythropoietin to nanoparticles made of lactic acid homopolymer or lactic acid/glycolic acid copolymer, mean nanoparticle size, and the resistance of the resulting complex to aggregation. The most effective sorption (greater than 80%) was achieved using a copolymer with equal proportions of lactic and glycolic acids (50:50). Experiments using an intracerebral post-traumatic hematoma model in rats demonstrated that nanosomal ls-rhEPO had neuroprotective actions, based on its ability to decrease death in the experimental animals (77.8% survived, which was 40% more than in the control group). Nanosomal ls-rhEPO was found to have no effect on hematopoiesis in conditions of chronic administration.

This study was aimed at developing a method for obtaining a nanosomal colloidal form of low-sialylated human erythropoietin (lsHEP) possessing neurotropic (antihemorrhage) activity. Parameters of HEP adsorption on nanoparticles of (i) homopolymer of lactic acid and (ii) copolymer of lactic and glycolic acids, average sizes of these nanoparticles, and aggregation stability of obtained complexes have been determined. The most effective adsorption (>80%) was achieved for a 50/50 copolymer of lactic and glycolic acids. Experiments on rats with intracerebral post-traumatic hematoma model showed that the obtained nanosomal lsHEP exhibited a significant neuroprotective effect, which was manifested by 40% reduced loss of test animals (77.8% survival). Chronic administration of nanosomal lsHEP did not influence hemopoiesis in the experimental animals.

Целью настоящего исследования являлась оценка влияния параметров процесса получения наносомальной лекарственной формы рифампицина (Rif) на основе полилактидов на размеры наночастиц, степень сорбции Rif, а также кинетику высвобождения Rif in vitro. Показано, что наиболее эффективной сорбции Rif в наночастицах (до 90 %) удается добиться при использовании полилактидов с дополнительными концевыми карбоксильными группами. Увеличение исходных концентраций Rif в органической фазе от 1 до 5 мг/мл приводит к некоторому снижению степени сорбции (с 89 до 76 %), однако не оказывает существенного влияния на размер получаемых наночастиц (190 - 260 нм). Изменение состава полимерной матрицы наночастиц позволяет регулировать скорость высвобождения из них Rif; при этом наличие дополнительных концевых карбоксильных групп в полилактидах обеспечивает более медленное высвобождение антибиотика, что объясняется его более прочным взаимодействием с полимерной матрицей.

Using of polylactic nanoparticles as the carries allows to elaborate intravenous formulation for the antituberculosis antibiotic rifabutin that is poor soluble in water. The peroral uptaking nanosomal form of the drug lead to two time more bioavailability of rifabutin comparing with usual formulation. References 1. Gelperina S.E., Maksimenko O.O., Vanchugova L.V., Shipulo E.V., Shandryuk G.A., Bondarenko G.N., Shvets V.I./ Him.-pharm. zhurnal. 2010. V. 44, № 3. P.11-17. 2. Bootz A., Vogel V., Schubert D., Kreuter J./ Eur. J. Pharm. Biopharm. 2004. V. 57, № 2. P. 369-375.

The aim of the present work was to assess the influences of the parameters of the process of preparing polylactide-based nanosomal medicinal formulations of rifampicin (Rif) on nanoparticle size, the level of Rif sorption, and the kinetics of Rif release in vitro. The most effective Rif sorption in nanoparticles (up to 90%) was obtained using polylactides with additional terminal carboxyl groups. An increase in the initial Rif concentration in the organic phase from 1 to 5 mg/ml led to some decrease in the extent of sorption (from 89% to 76%) though it had no significant effect on the sizes of the resulting nanoparticles (190 – 260 nm). The rate of Rif release could be controlled by altering the composition of the polymer matrix of the nanoparticles; the presence of additional terminal carboxyl groups in polylactides gave slower antibiotic release, resulting from tighter interaction with the polymer matrix.

A nanosomal formulation of moxifloxacin has been prepared by anionic polymerization of poly(butyl-2-cyanoacrylate) in the presence of the drug. The poly(butyl-2-cyanoacrylate) nanoparticles absorb effectively moxifloxacin with a high total content and have a considerable capacity (> 45%). The influence of reaction parameters such as pH and drug-to-polymer ratio on the nanoparticle characteristics has been studied. The efficacy of the novel formulation has been evaluated in mice infected with M. tuberculosis. It is shown that the efficacy of the proposed nanosomal formulation for i.v. administration evaluated by a decrease in the lung mycobacteria count is more than twice that of a reference preparation.

Nanosomal formulation of moxifloxacin has been prepared by anionic polymerization of poly(butyl-2-cyanoacrylate) in the presence of the drug. Poly(butyl-2-cyanoacrylate) nanoparticles enables effective sorption of moxifloxacin with a high total content and considerable capacity of nanoparticles (>45%). The influence of the reaction parameters such as pH and drug-to-polymer ratio on the characteristics of the nanoparticles has been studied. Efficacy of the novel formulation has been evaluated in mice infected withM. tuberculosis. It is shown that the efficacy of the proposed nanosomal formulation for intravenous administration evaluated by a decrease in the mycobacteria count in lungs is more than twice greater as compared to that of a reference preparation.