Nanoformulations for Therapy of Pancreatic and Liver Cancers

Abstract

Pancreatic and liver cancers often have poor prognoses. Clinically, pancreatic and liver cancer requires early diagnosis, and surgery is often associated with tumor recurrence. Currently, chemotherapies are limited in their ability to accurately target the tumors, and are associated with significant toxicity in patients. Targeting of chemotherapy can be improved by encapsulation in nanocarriers. A variety of preclinical studies indicate relatively superior therapeutic outcomes compared with drug alone therapy. Targeted nanoparticle imaging agents may also additionally facilitate better diagnosis and improve patient outcomes. This review discusses the nanoformulations that are under investigation (mainly preclinical studies, but also with some current clinical trial examples) against pancreatic and liver cancers, understands the challenges and provides future perspectives.

Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer

“…Nanoparticle carriers with appropriately tailored physico chemical characteristics (including optimal size, charge, shape, and drug loading and release), which can protect their cargo (the drug) from premature release and degradation, and can traverse the various biological barriers to drug delivery, have the potential to improve therapeutic efficacy in patients with PDAC (BOX 2). Indeed, advances in nanotechnology have been leveraged for improved drug-delivery strategies for a variety of therapeutic and diagnostic agents 18 . For example, several nano formulations of gemcitabine have been evaluated in preclinical and clinical studies [19][20][21][22][23] .…”

Dual-Responsive Core Crosslinking Glycopolymer-Drug Conjugates Nanoparticles for Precise Hepatocarcinoma Therapy

“…Human hepatocellular carcinoma (HCC) is a common type of primary liver cancer and is diagnosed in more than half a million people worldwide ( de Souza et al, 2015 ). At present, HCC has received increasing attention because of its important effect on the physiological functions of the liver, high lethality, and the growing incidences in many regions ( Torre et al, 2015 ).…”

Development of a lipoid microbubble formulation and in vitro evaluation assisted by ultrasound

“…The organelles inside the cells are simplified for a better demonstration, intracellular organelles images are taken with permission from Servier Medical Art In the case of chemotherapeutics many lack specificity for the proposed site of action resulting in both healthy and cancerous cells being affected, which leads to debilitating side effects. Nano carrier systems, with ability to preferentially deliver and trap chemotherapeutics in tumour site thus minimising the exposure of healthy tissues to the cytotoxic drugs, are proposed as ideal vectors tomitigate the incidence and severity of side effects (2). The phenomenon is referred to as the enhanced permeation and retention (EPR) effect, which is due to the immature vasculature system in tumours (Figure 1-1).…”

“…US exposure study design: US is applied from underneath of well in a 24 well plate, a coupling gel was used between the US probe and well plateIt was observed that using JUS2 at its highest intensity (i.e. intensity of 2.5 W/cm2 and 100% duty cycle), any volumes more than 2.25 mL/well (in a 24 well plate) would lead to formation of condensate (as a result of agitation caused by US) on the ceiling of the lid inserted over the samples. This could consequently change the final volume of the samples causing variations between each treatment.…”

“…Optical density results, time kill study using P. aeruginosa ATCC ® 27853 ™ , effect of LMBs+10 sec US on bactericidal activity of ciprofloxacin HCl (0.25 µg/mL), the readings are from before (time=0), and5 min, 2, 4, 6 and 8 hours after the US treatment, the control group does not contain drug nor LMBs confirming the exponential growth of the bacteria, the interferences caused by LMBs are subtracted from each of the readings in the arms containing LMBs, the US parameters were: A) 1 MHz, 100% duty cycle and intensity of 2.5 W/cm 2 , B) 1 MHz, 50% duty cycle and intensity of 3 W/cm 2 , C) 3 MHz, 100% duty cycle and intensity of 2.5 W/cm 2 , D) 1 MHz, , 50% duty cycle and intensity of 3 W/cm2 , the cells were cultured at 37 ºC in MH cationic adjusted broth (the data shown are mean ± SD) Colony counting via quantitative culturing…”