Drug and Alcohol Rehabilitation: VIP-Targeted Cytotoxic Nanomedicine for Breast Cancer.

VIP-targeted Cytotoxic Nanomedicine for Breast Cancer.

Filed under: Drug and Alcohol Rehabilitation

Drug Deliv Transl Res. 2012 Dec 1; 2(6): 454-462
Dagar A, Kuzmis A, Rubinstein I, Sekosan M, Onyuksel H

Cancer chemotherapy is hampered by serious toxicity to healthy tissues. Conceivably, encapsulation of cytotoxic drugs in actively-targeted, biocompatible nanocarriers could overcome this problem. Accordingly, we used sterically stabilized mixed micelles (SSMM) composed of biocompatible and biodegradable phospholipids to solubilize paclitaxel (P), a hydrophobic model cytotoxic drug, and deliver it to breast cancer in rats. To achieve active targeting, the surface of SSMM was grafted with a ligand, human vasoactive intestinal peptide (VIP) that selectively interacts with its cognate receptors overexpressed on breast cancer cells. We found that even in vitro cytotoxicity of P-SSMM-VIP was 2-fold higher that that of free paclitaxel (p<0.05). Given the unique attributes of P-SSMM and P-SSMM-VIP, most notable small hydrodynamic diameter (~15nm) and stealth properties, biodistribution of paclitaxel was significantly altered. Accumulation of paclitaxel in breast tumor was highest for P-SSMM-VIP, followed by P-SSMM and Cremophor based paclitaxel (PTX). Importantly, bone marrow accumulation of paclitaxel encapsulated in both SSMM-VIP and SSMM was significantly less than that of PTX. Administration of clinically-relevant dose of paclitaxel (5mg/kg) as P-SSMM-VIP and P-SSMM eradicated carcinogen-induced orthotopic breast cancer in rats, whereas PTX decreased tumor size by only 45%. In addition, a 5-fold lower dose (1mg/kg) of paclitaxel in actively targeted P-SSMM-VIP was associated with ~80% reduction in tumor size while the response to PTX and P-SSMM was significantly less. Hypotension was not observed when VIP was grafted onto SSMM. Based on our findings, we propose further development of effective and safe VIP-grafted phospholipid micelle nanomedicines of anti-cancer drugs for targeted treatment of solid tumors in humans. HubMed – drug


Apoptotic and Immune Restoration Effects of Ganoderic Acids Define a New Prospective for Complementary Treatment of Cancer.

Filed under: Drug and Alcohol Rehabilitation

J Clin Cell Immunol. 2011 Dec 11; S3: 4
Radwan FF, Perez JM, Haque A

Considering the fact that a key factor in tumor development is the evasion of immune detection, the search for natural products, which have reduced toxicity towards normal tissues as well as immunostimulatory capabilities has received growing interest. One attractive source of antitumor products is the Ganoderma lucidum mushroom, which has been used for centuries as an herbal medicine for the prevention and treatment of a variety of diseases, including cancer, and has been shown to improve immune function. Interestingly, its methanol soluble triterpenoid extracts, namely Ganoderic Acids (GAs), have been the subject of several recent investigations on their chemotherapeutic effects. While current research has revealed GAs’ role in inducing apoptosis of cancer cells with a much lower toxicity to healthy cells, little information is available on their in vitro and/or in vivo immune activities. In this review, we aim to discuss the current knowledge on GAs, and their potential as apoptosis inducing as well as immune activating molecules that could be a potential alternative approach for designing novel chemoimmunotherapeutics against malignant diseases. We also discuss other new approaches for exploiting the advantages of using a nanoparticle polymer-GA conjugate as a tool for a sustained and targeted delivery of drug in vivo.
HubMed – drug


Rapid crystallization of glycine using metal-assisted and microwave-accelerated evaporative crystallization: the effect of engineered surfaces and sample volume.

Filed under: Drug and Alcohol Rehabilitation

Nano Biomed Eng. 2012; 4(3): 125-131
Grell TA, Pinard MA, Pettis D, Aslan K

Metal-Assisted and Microwave-Accelerated Evaporative Crystallization (MA-MAEC), is a new approach to crystallization of drug compounds, amino acids, DNA and proteins. In this work, we report our additional findings on the effect of engineered surfaces and sample volume on the rapid crystallization of glycine. With the use of hydrophilic functionalized surfaces and the MA-MAEC technique, glycine crystals ~1 mm in size were grown in 35 seconds with 100% selectivity for the ?-form.The use of moderately hydrophobic surfaces resulted in the growth of glycine crystals only at room temperature. An increase in volume of initial glycine solution (5-100 ?L) resulted in an increase in crystal size without a significant increase in total crystallization time. Raman spectroscopy and powder X-ray diffraction results demonstrated that the glycine crystals grown on engineered surfaces were structurally identical to those grown using conventional evaporative crystallization.
HubMed – drug


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