Evaluation of nanoparticle size from TEM images using ImageJ software

Evaluation of nanoparticle size from TEM images using ImageJ software. 2]. Despite improvements in the field of medical procedures, chemotherapy, and radiation therapy, the prognosis of pancreatic malignancy remains extremely poor with a 1- to 5-12 months overall survival rate of about 25% and 6%, respectively, which is the least expensive among common malignancies [3]. None of the current chemotherapy regimens provide more than one-year survival benefit. Gemcitabine is the most commonly used chemotherapy for pancreatic malignancy, which improves overall survival rate by about 6.7 months. A recent FDA approved combination treatment regimen of Abraxane? Nanchangmycin (a human serum-bound paclitaxel nanoparticle formulation) with gemcitabine has only increased overall survival to 8.5 months. Therefore, it is usually imperative to develop new chemotherapeutic approaches to further improve the clinical end result of pancreatic malignancy patients. Many new drug(s) and drug combination based therapeutic regimens have resulted in poor patient tolerance, drugs low half-life, low cellular uptake, and high systemic toxicity [4C7]. Such therapeutic options largely fail in Phase II or Phase III trials and thus cause huge financial burdens. Thus, repurposing of drugs that are already approved for human use for other indications seems to be a encouraging new treatment option for malignancy [8C10]. The advantages Nanchangmycin of such strategy are fewer restrictions by FDA for clinical trials and the possibility of quick translation to the clinic. A recent example of drug repurposing is usually metformin (a drug for diabetes treatment), which has shown potent malignancy chemopreventive and chemotherapeutic activities [11C13]. Ormeloxifene (ORM), a non-steroidal molecule which is Nanchangmycin usually widely used as an oral contraceptive in humans [14, 15], can be repurposed for cancer treatment. This is a potent agent that has been widely shown to act upon several important molecular targets in cancer [16]. ORM has shown greater protective effects on strains TA97a, TA98, TA100 and TA102 than Tamoxifen [17]. Interestingly, ormeloxifene induces significant tumor growth inhibition in rat model [17]. More importantly, a Phase II clinical study in 70 female patients, achieved ~38.7% overall response rate with 6 months of ormeloxifene treatment [18]. Recent studies from our lab and others suggest an anti-tumorigenic effect of ORM in various cancers, such as ovarian, breast, head and neck, and chronic myeloid leukemia [18C24]. Its inhibitory activity of highly tumorigenic and metastatic pancreatic cancer cells provides strong rationale to implement this molecule for anti-cancer applications. Another reason for choosing this molecule for cancer therapeutics is because it exhibits excellent therapeutic index with no systemic toxicity at chronic administration [25]. All these studies indicate that ormeloxifene is an excellent drug candidate for cancer treatment. Pancreatic ductal adenocarcinoma exhibits several pathological features that lead Rabbit Polyclonal to FZD9 to disorganized, leaky and nonfunctional vasculature [26C28], dense stroma [29], and deregulated cellular transport proteins [30]. This leads to ineffective drug delivery and drug resistance by creating high interstitial fluid pressure [31], preventing the movement of chemotherapy from the vasculature to the extracellular compartment. This complexity suggests that an efficient Nanchangmycin delivery of ormeloxifene is highly desirable to effectively eradicate pancreatic cancer cells. Delivery of drugs using nanocarrier(s) can easily pass the pores in leaky endothelial cells ranging as low as 100 to 780 nm [32, 33] and result in clusters around the neoplastic cells and prolonged drug release. Poly(lactide-and use. This formulation was named PLGA-ORM20. Similarly, PLGA-ORM formulations with 5, 10, 15, and 25 mg ORM were prepared and termed as PLGA-ORM5, PLGA-ORM10, PLGA-ORM15, and PLGA-ORM25, respectively. Additionally, parent PLGA NPs were also prepared without ORM that can serve as a control for all and experiments. The PLGA-ORM 20 formulation was used for all and experiments. In the results and discussion sections the PLGA-ORM 20 formulation was designated as PLGA-ORM NPs. 2.4. PLGA-ORM NPs characterization 2.4.1. Particle size PLGA-ORM NPs were characterized for the surface morphology and size of particles using a JEOL-1210 transmission electron microscope (TEM) (JEOL.