Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the major problems raised by the microencapsulation of drugs which are sparingly soluble in water is the difficulty to achieve a controlled and total release of the drug. It was previously shown that the microencapsulation of a model water insoluble drug, namely 1-[2-(4-fluorobenzoyl)aminoethyl]-4-(7-methoxynaphthyl) piperazine hydrochloride (FAMP) with a hydrophilic additive like low molar mass poly(ethylene glycol)s (PEG) can fulfil these requirements, provided all the drug + additive matter is in contact with the surrounding liquid medium via open pores and percolating channels. In this paper, PEG was replaced by other additives, selected because of their potential ability to increase the solubility of FAMP in pH = 7.4 isosomolar phosphate buffer (PBS). The idea was that increasing the solubility locally in microparticles could allow the drug to be released, despite its poor solubility in aqueous media like body fluids, and be absorbed before recrystallization. The solubility in PBS of FAMP mixed with additive, in the form of solid dispersions, was determined for various additives, namely citric acid, dimyristoyl DL-alpha-phosphatidyl choline (DMPC), poloxamer copolymers of different compositions and poly(dodecyl L-lysine citramidate) (PLCAC12(100)), an aggregate-forming hydrophilic polyelectrolyte containing 100%, hydrophobizing ester groups which can accommodate lipophilic compounds in hydrophobic pockets present in the aggregates. PEG was taken as a reference. It was found that DMPC, some poloxamers and the hydrophobized polyelectrolyte do increase the solubility of FAMP in PBS. Investigation was made of the release of FAMP from ground microparticles, whose loads were composed of FAMP combined with these solubilization-promoting additives. It was found that the release rate of FAMP from such systems can be increased and modulated to achieve an in vitro sustained release over a 20-30 day period and secure exhaustion of the particles at the end of this period.
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PMID:The use of additives to modulate the release of a sparingly water soluble drug entrapped in PLA50 microparticles. 1067 Sep 42

Plasmacytoid dendritic cells (DC) are known to produce large amounts of IFN-alpha when stimulated with virus in vivo and in vitro. Immunohistological staining of spleens from mice taken at different times after HSV infection revealed an early infiltration of plasmacytoid DC whereas both the myeloid DC and lymphoid-related DC had different kinetics. Upon rechallenge with virus in vitro, total splenic DCs from viral-infected mice were unable to produce IFN-alpha when compared with DC from mice that received an initial in vivo injection with PBS. Furthermore, DC from mice that were infected with increasing doses of HSV expressed high levels of accessory and activation molecules compared with control mice. However, when cultured in vitro together with allogeneic T cells, DC from mice that had been exposed to the highest viral titers in vivo induced the lowest levels of T cell proliferation. DC exposed to PBS in vivo promoted a Th1 response upon coculture with CD4(+) T cells whereas T cells cultured with DC exposed to increasing viral titers in vivo resulted in a gradually decreased Th1 response. The data suggest HSV induces DC maturation and at higher titers, exhaustion, diminishing T cell proliferation, and IFN-gamma secretion.
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PMID:Dendritic cells exposed to herpes simplex virus in vivo do not produce IFN-alpha after rechallenge with virus in vitro and exhibit decreased T cell alloreactivity. 1510 Feb 80