Gemcitabine Combination Nano Therapies for Pancreatic Cancer

Abstract

Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely to patients is needed. Nanoparticle-mediated delivery can offer to load a cocktail of drugs, increase stability and availability, on-demand and tumor-specific delivery while minimizing chemotherapy-associated adverse effects. This review discusses the available drugs being co-administered with GEM and the limitations associated during the process of co-administration. This review also helps in providing knowledge of the significant number of delivery platforms being used to overcome problems related to gemcitabine-based co-delivery of other chemotherapeutic drugs, thereby focusing on how nanocarriers have been fabricated, considering the modes of action, targeting receptors, pharmacology of chemo drugs incorporated with GEM, and the differences in the physiological environment where the targeting is to be done. This review also documents the focus on novel mucin-targeted nanotechnology which is under development for pancreatic cancer therapy.

In Vivo Assessment of Thermosensitive Liposomes for the Treatment of Port Wine Stains by Antifibrinolytic Site-Specific Pharmaco-Laser Therapy

“…Consequently, TA release at T ≈ T m as well as at T > T m would be desirable. Currently, it is unknown whether TA release occurs in the L α phase of DPPC bilayers, as has been reported for other molecules [ 67 , 68 ]. TA release from DPPC:DSPE-PEG (96:4) and DPPC:MPPC:DSPE-PEG (86:10:4) LUVETs was therefore investigated at T > T m during 5 min of heating, i.e., in line with the thrombus dynamics [ 15 ] and previously established complete release times [ 16 ].…”

Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells

“…Previous reports showed that the imidazolidone group of biotin forms hydrogen bonds with the imidazole ring of histidine when adsorbed to proteins during accumulation inside tumor cells [50]. Similarly, hydrogen bonding between the biotin ring and imidazolidone group of gemcitabine ( Figure 3B) probably increases the drug-loading capacity [51]. Electrostatic interactions between the drug and the unmodified carboxylate group of PG4.5 may also increase the gemcitabine-loading content of the nanoparticles.…”

Actively Targeted Nanodelivery of Echinomycin Induces Autophagy-Mediated Death in Chemoresistant Pancreatic Cancer In Vivo

“…Mice (7 mice/group) were implanted with S2VP10 and S2CP9 cells as stated above. Seven days, (S2VP10) or ten days (S2CP) post-implantation, mice were treated with PBS, 50 mg/kg Gemzar [64,65], 10 µg/kg of echinomycin [62], or 10µg/kg SDC1-Lip echinomycin injected iv weekly for 3 weeks. Mouse survival was assessed as a measure of tumor response because ATP levels measured using bioluminescence imaging are not appropriate with autophagy [17,66].…”