It has been suggested to use surfactant mrcelles as mrcrocontamers for mcreasmg the efficiency of neurolephc targeting from blood flow mto the bram The neuroleptrc actron of halopendol, mtrapentoneally injected mto mtce m mmellar solutron of non-iomc block copolymer surfactant (pluromc P-85) m water, increased several-fold tf compared with that observed for halopendol aqueous solutron Incorporatron of bram-specific antibodies mto halope~dol~onta!nlng mtcelles resulted m addrtronal drasuc increase (more than by 2 orders of magnitude) m the drug effect Neuroleptrcs, Haloperrdol, Hematoenceph~lc barrter, Directed transport, Mtcelle, Pluromc P-85
A tool was developed for enhancement of plasmid penetration into an intact cell, based on increasing DNA hydrophobicity via inclusion into a soluble interpolyelectrolyte complex (IPC) with polycations. The characteristics of formation of DNA IPC with synthetic polycations [poly(N-ethyl-4-vinylpyridinium)bromide (PVP) and PVP modified with 3% of N-cetyl-4-vinylpyridinium units (PVP-C)] were studied using ultracentrifugation and polyacrylamide gel electrophoresis methods. The conditions were established under which the mixing of DNA and polycation aqueous solutions results in the self-assembly of soluble IPC species. Incorporation of DNA into IPC results in the enhancement of DNA binding with isolated Bacillus subtilis membranes. A considerable increase in the efficiency of transformation of B. subtilis cells with pBC16 plasmid resulted from incorporation of the plasmid into the IPC with PVP and CVP.
In human erythrocyte membranes incubated with [adenylate‐32P]NAD the 36 kDa protein is predominantly labeled. The labeling is greatly stimulated by nitroprusside in the presence of dithiothreitol. We have purified the 36 k Da protein and identified this modification as crysteine‐specific mono(ADP‐ribosylation) because: (i) labeling occured only when [32P]NAD was replaced by adenine [U‐14C]NAD, but not by [carbonyl‐14C]NAD; (ii) treatment of the prelabeled protein with snake venom phosphodiesterase led to releasing 5′‐[32P]AMP; (iii) the bond between the protein and the nucleotide was hydrolyzed by HgCl2, but was resistant to hydroxylamine. The 36 kDa protein reacted on Western blots with two different monoclonal antibodies (MAbs) against glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and was immunoprecipitated by both MAbs.
To enhance the penetration of oligonucleotide ("oligo') into cells, the &go was combined with the hydrophobic undccyl residue. Using the 'DNAsynthesator', we synthesized oligo, complementary to the loop-forming site of the RNA, encoding polymerase 3 of the iniluenza virus (type A), and comb&d it with the undecyl residue added to the 5' terminal phosphate group. It was found that the modified oligo effectively suppresses the influenza AIPR8j34 (HINI) virus reproduction and inhibits the synthesis of virus-specific proteins in MDCK cells. Under the same conditions, the non-modified antisense otigo and modified nonsense oligo did not affect the virus development.
Co-encapsulation of abiraterone acetate (AbrA) and docetaxel (Dtx) in polymeric nanoparticles as novel prototypes for prostate cancer treatment combining hormonal and chemotherapy was designed. Nanoparticles (NPs) composed of poly(DL-lactide-co-glycolide) (PLGA) were prepared by singleemulsion solvent evaporation technique and characterized in terms of morphology with atomic force microscopy and transmission electron microscopy. HPLC method for simultaneous determination of AbrA and Dtx encapsulation efficacy was developed. Also differential scanning calorimetry and Fouriertransform infrared spectroscopy were provided. To study the effectiveness of cellular internalization and distribution of NPs with AbrA and Dtx co-encapsulation (NP-AbrA/Dtx), a fluorescence microscopy was utilized. NPs prepared had size 256.3 AE9.4 nm and zeta potential −18.4 AE1.4 mV. Encapsulation efficacy for AbrA was 68.7% and for Dtx was 74.3%. NPs were able to control the AbrA and Dtx release within 24 h. The mathematical model of drug release was performed. The results obtained from confocal microscopy showed the effective accumulation of the NP-AbrA/Dtx in the cytoplasm of cells. Synthesized NPs possessed satisfactory parameters and a biphasic release profile, proceeding by the Fick diffusion mechanism, which provide prolonged release of the drugs and maintenance of their concentration. It was shown that NPs loaded with AbrA and Dtx exhibited a high cytotoxic activity on the LNCaP cell line, similar to the combination of free drugs of AbrA and Dtx, but in contrast to the combination of substances, had a synergistic mechanism of action. Our findings support the potential use of developed NPs in further in vivo studies.How to cite this article: Sokol MB, Nikolskaya ED, Yabbarov NG, Zenin VA, Faustova MR, Belov AV, Zhunina OA, Mollaev MD, Zabolotsky AI, Tereshchenko OG, Severin ES. 2019. Development of novel PLGA nanoparticles with co-encapsulation of docetaxel and abiraterone acetate for a highly efficient delivery into tumor cells. J Biomed Mater Res Part B 2019:107B:1150-1158.
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