International journal of pharmaceutics
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Comparative Study
Evaluation of pharmacokinetic properties and anaesthetic effects of propofol in a new perfluorohexyloctane (F6H8) emulsion in rats--A comparative study.
Propofol (2,6-diisopropylphenol) is a safe and widely used anaesthetic, but due to low water solubility and high lipophilicity a difficult compound to formulate. The solubility of propofol in the semifluorinated alkane perfluorohexyloctane (F6H8) is very high (>300 mg/ml). In the present work we investigate if a F6H8-based emulsion could be used as a new intravenous drug delivery system for propofol from a pharmacokinetic, pharmacodynamic and safety point of view. ⋯ A slightly increased alanine aminotransferase (ALT) was measured after multiple application of the F6H8-propofol emulsion. In conclusion, the F6H8-propofol emulsion showed no significant different pharmacokinetics and sedation properties, compared to a commercial soy-based propofol emulsion. Further, no toxic effects could be detected on the F6H8 emulsion indicating it was a safe excipient in rats.
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RNA interference is an effective method to achieve highly specific gene regulation. However, the commonly used cationic liposomes have poor biocompatibility, which may lead to systematic siRNA delivery of no avail. PEGylation is a good strategy in shielding the positive charge of cationic liposomes, but the enhanced serum stability is often in company with compromised cellular uptake and endosome escape. ⋯ In contrast with normal PEGylation, hyaluronic acid and PEG co-modified PEG-HA-NP provided comparable cellular uptake and P-glycoprotein downregulation efficacy in MCF-7/ADR cells compared with Lipofectamine RNAiMAX and naked NP regardless of its anionic charged surface. Because of its good biocompatibility in serum, PEG-HA-NP possessed the best tumor accumulation, cellular uptake and subsequently the strongest P-glycoprotein silencing capability in tumor bearing mice compared with naked NP and HA-NP after i.v. injection, with a 34% P-glycoprotein downregulation. Therefore, PEG-HA coated liposomal complex was demonstrated to be a promising siRNA delivery system in adjusting solid tumor P-glycoprotein expression, which may become a potential carrier in reversing MDR for breast cancer therapy.
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Comparative Study
L-Carnitine ester of prednisolone: pharmacokinetic and pharmacodynamic evaluation of a type I prodrug.
To evaluate whether PDSC, an L-carnitine ester derivative of prednisolone and OCTN2 substrate, could provide a targeted delivery of the corticosteroid into the lung tissues of an asthmatic guinea pig model. ⋯ The collective data suggest that PDSC has the potential to be an effective prodrug for the treatment of asthma with concomitant reduction in systemic side effects, and that novel prodrugs produced by L-carnitine conjugation can have useful applications in the targeted accumulation of drugs in the lungs.
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Broad-spectrum antimicrobial agents, such as silver, are increasingly being formulated into medicated wound dressings in order to control colonization of wounds by opportunistic pathogens. Medicated wound dressings have been shown in-vitro to be effective against planktonic cultures, but in-vivo bacteria are likely to be present in biofilms, which makes their control and eradication more challenging. Recently, a functional wound dressing (AQUACEL(®) Ag+ Extra™ (AAg + E)) has been developed that in addition to silver contains two agents (ethylenediaminetetraacetic acid (EDTA) and benzethonium chloride (BC)) designed to disrupt biofilms. ⋯ The biofilm was seen to remain viable in the presence of unmedicated dressing, silver-containing dressing or silver nitrate solution. In the presence of AAg + E, however, the biofilm was eradicated. Control experiments showed that neither EDTA nor BC alone had a bactericidal effect, which means it is the synergistic action of EDTA and BC disrupting the biofilm with silver being bactericidal that leads to the product's efficacy.
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Although bacterial nanocellulose (BNC) may serve as an ideal wound dressing, it exhibits no antibacterial properties by itself. Therefore, in the present study BNC was functionalized with the antiseptic drug octenidine. Drug loading and release, mechanical characteristics, biocompatibility, and antimicrobial efficacy were investigated. ⋯ In biological assays, drug-loaded BNC demonstrated high biocompatibility in human keratinocytes and antimicrobial activity against Staphylococcus aureus. In a long-term storage test, the octenidine loaded in BNC was found to be stable, releasable, and biologically active over a period of 6 months without changes. In conclusion, octenidine loaded BNC presents a ready-to-use wound dressing for the treatment of infected wounds that can be stored over 6 months without losing its antibacterial activity.