A versatile theranostic agent that integrated with therapeutic and diagnostic functions is extremely essential for cancer theranostic. Herein, a multifunctional theranostic nanoplatform (PFP@MPDA-DOX) based on perfluoropentane (PFP) encapsulated mesoporous polydopamine (MPDA) is elaborately designed, followed by gating of drug doxorubicin (DOX) for preventing cargo leaking. The MPDA with pH-responsive biodegradation behavior was served as nanocarrier, which also endows the nanoplatform with a large cavity for PFP filling. The nanoparticles were then gated with DOX molecule by Michael addition and/or Schiff base reaction to shield the leaking of PFP during the blood circulation before the tumor tissue is reached. Also, such nanotheranostic exhibits high photothermal conversion efficiency of 45.6%, which can act as an intelligent nanosystem for photothermal therapy (PTT) and photoacoustic (PA) imaging. Moreover, the liquid-gas phase transition of PFP arising upon exposure to an 808 nm laser and thus produced the bubbles for ultrasound (US) imaging. The subsequent PFP@MPDA-DOX-mediated synergetic chemotherapy (contributed by the DOX gatekeeper) and PTT (contributed by the MPDA) shows excellent anticancer activity, which has been systematically evaluated both
Objective To investigate the effects of sevoflurane on the expression of protein kinase C-α(PKC-α)in ischemia-reperfusion rat lungs. Methods 96 adult male wistar rats weighing 250~350 g were randomly divided into 4 groups:group C (n=24):continuous perfusion without ischemia;group IR(n =24):occlusion of the left pulmonary hilum for 45 min,followed by reperfusion;group sev-C(n =24):1MAC sevoflurane inhalation for 30 min,followed by continuous perfusion;group sev-IR (n=24):1MAC sevoflurane inhalation followed by ischemia- reperfusion. The lung wet-to-dry weight ratio (W/D)and lung permeability index (LPI)were calculated. The expressions of PKC-α in cytoplasm and cell membrane were determined by Western blot. Results W/D and LPI increased progressively after reperfusion in IR and sev-IR groups(P 0.05). Moreover,preadministration of sevoflurane could inhibit the increase of W/D and LPI(P 0.05). The expression of PKC-α in group IR in cellular membrane increased obviously after reperfusion (P 0.05),while in cytoplasm it decreased accordingly (P 0.05). The inhalation of sevoflurane could inhibit the change of PKC-α(P 0.05). Conclusion The activation and shifting of PKC-α may be associated with the lung injury after reperfusion. Sevoflurane inhibits the activation and shifting of PKC-α and protect the pulmonary function.
Abstract Objectives This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Key findings Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, ‘real-time’ in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Summary Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro–in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable.