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透皮淋巴靶向长春新碱传递体 总被引:3,自引:0,他引:3
长春新碱(vincristine,VCR)临床主要用于治疗急性淋巴细胞白血病、何杰金及非何杰金淋巴瘤,疗效确切,但由于具有较大的神经系统毒性和局部刺激性,限制了其在临床上的应用。为增加VCR的淋巴靶向性,以增强疗效,降低其毒副作用,采用薄膜-超声分散法制备长春新碱传递体(VCR-T),并考察其制剂学性质、药代动力学特征及靶向性。所制备的VCR-T平均粒径为63 nm,包封率为59%;改良Franz扩散池研究发现其体外透皮过程符合多项式方程,12 h累积透皮百分率为67.4%;HPLC法测定VCR在大鼠体内的药代动力学及组织分布,以VCR注射液为对照,VCR-T使VCR在血液中滞留时间延长了12倍,大鼠淋巴中靶向指数增加了2.75倍。传递体可良好地载带VCR透过皮肤进入体循环,具有较好的淋巴靶向性,可作为新型的淋巴靶向给药系统。 相似文献
25.
《Journal of drug targeting》2013,21(5):401-415
Molecular imaging is a relatively new discipline with a crucial role in diagnosis and treatment tracing of diseases through characterization and quantification of biological processes at cellular and sub-cellular levels of living organisms. These molecular targeted systems can be conjugated with contrast agents or radioligands to obtain specific molecular probes for the purpose of diagnosis of diseases more accurately by different imaging modalities. Nowadays, an interesting new approach to molecular imaging is the use of stealth nanosized drug delivery systems such as liposomes having convenient properties such as biodegradability, biocompatibility and non-toxicity and they can specifically be targeted to desired disease tissues by combining with specific targeting ligands and probes. The targeted liposomes as molecular probes in molecular imaging have been evaluated in this review. Therefore, the essential point is detection of molecular target of the disease which is different from normal conditions such as increase or decrease of a receptor, transporter, hormone, enzyme etc, or formation of a novel target. Transport of the diagnostic probe specifically to targeted cellular, sub-cellular or even to molecular entities can be performed by molecular imaging probes. This may lead to produce personalized medicine for imaging and/or therapy of diseases at earlier stages. 相似文献
26.
Mohammed H. Elkomy Shahira F. El Menshawe Rasha M. Kharshoum Amany M. Abdeltwab Raghda R. S. Hussein Doaa S. Hamad Izzeddin Alsalahat Heba M. Aboud 《Drug delivery》2022,29(1):2058
Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β2-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity. 相似文献
27.
Fei Gao Chenyu Peng Jindian Li Rongqiang Zhuang Zhide Guo Duo Xu Xinhui Su Xianzhong Zhang 《Journal of labelled compounds & radiopharmaceuticals》2019,62(7):301-309
A novel 131I‐radiolabeled probe with aromatic boronate motif (131I‐EIPBA) was designed to target progesterone receptor (PR)–positive breast cancer with enhanced nucleus uptake. Acetylene progesterone was conjugated with pegylated phenylboronic acid via click reaction and radiolabeled with 131I to afford 131I‐EIPBA. Meanwhile, 131I‐EIPB without boronate was prepared as control agent. After determination of the lipophilicity and stability of these tracers, in vitro cell uptake studies and in vivo biodistribution in rats were performed to verify the enhanced nucleus uptake and PR targeting ability of 131I‐EIPBA. 131I‐EIPBA was obtained with moderate radiochemical yield (40.35 ± 3.52%) and high radiochemical purity (>98%). As expected, the high binding affinity (39.58 nM) of 131I‐EIPBA for PR was determined by cell binding assay. The internalization ratio of 131I‐EIPBA was remarkably higher than that of 131I‐EIPB in PR‐positive MCF‐7 cells. Furthermore, the enhanced nucleus uptake of 131I‐EIPBA (0.59 ± 0.02%) was found to be significantly higher than that of 131I‐EIPB (0.13 ± 0.01%) in MCF‐7 cells. A novel 131I‐EIPBA compound was developed for PR targeting with improved cellular nucleus uptake. Furthermore, the introduction of aromatic boronate motif provides a worthwhile strategy for enhancing the nuclear receptor targeting of tracers. 相似文献
28.
《Expert opinion on drug delivery》2013,10(6):747-760
Objectives: In this study, the authors developed d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) liposomes and further conjugated them to trastuzumab for controlled and targeted delivery of docetaxel (DTX) as a model hydrophobic drug. Methods: DTX- or coumarin-6-loaded liposomes were prepared by solvent injection method and characterized for size and size distribution, surface charge, surface chemistry and drug encapsulation efficiency and drug release profile. SK-BR-3 cells were employed as an in vitro model for HER2-positive breast cancer and assessed for their cellular uptake and cytotoxicity of the two liposomal formulations. In vivo pharmacokinetics (PK) was investigated in Sprague–Dawley rats. Results: The IC50 value was found to be 20.23 ± 1.95, 3.74 ± 0.98, 0.08 ± 0.4 μg/ml for the marketed preparation of DTX, TPGS liposomes and trastuzumab-conjugated TPGS liposomes, respectively after 24 h incubation with SK-BR-3 cells. In vivo PK experiments showed that i.v. administration of trastuzumab-conjugated liposomes achieved 1.9 and 10 times longer half-life, respectively than PEG-coated liposomes and DTX. The area under the curve (AUC) was increased by 3.47- and 1.728-fold, respectively. Conclusion: The trastuzumab-conjugated vitamin E TPGS-coated liposomes showed greater potential for sustained and targeted chemotherapy in the treatment of HER2 overexpressing breast cancer. 相似文献
29.
《Pharmaceutical development and technology》2013,18(4):331-342
Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon. 相似文献
30.
《Expert opinion on drug delivery》2013,10(7):889-905
Introduction: With the advancement in the field of medical colloids and interfacial sciences, the life expectancy has been greatly improved. In addition, changes in the human lifestyle resulted in development of various organic and functional disorders. Central nervous system (CNS) disorders are most prevalent and increasing among population worldwide. The neurological disorders are multi-systemic and difficult to treat as portal entry to brain is restricted on account of its anatomical and physiological barrier. Areas covered: The present review discusses the limitations to CNS drug delivery, and the various approaches to bypass the blood brain barrier (BBB), focusing on the potential use of solid lipid nanoparticles (SLN) for drug targeting to brain. The methods currently in use for SLN production, physicochemical characterization and critical issues related to the formulation development suitable for targeting brain are also discussed. Expert opinion: The potential advantages of the use of SLN over polymeric nanoparticles are due to their lower cytotoxicity, higher drug loading capacity and scalability. In addition, their production is cost effective and the systems provide a drug release in a controlled manner up to several weeks. Drug targeting potential of SLN can be enhanced by attaching ligands to their surface. 相似文献