Optimised Electroporation for Loading of Extracellular Vesicles with Doxorubicin

The clinical use of chemotherapeutics is limited by several factors, including low cellular uptake, short circulation time, and severe adverse effects. Extracellular vesicles (EVs) have been suggested as a drug delivery platform with the potential to overcome these limitations. EVs are cell-derived, lipid bilayer nanoparticles, important for intercellular communication. They can transport bioactive cargo throughout the body, surmount biological barriers, and target a variety of tissues. Several small molecule drugs have been successfully incorporated into the lumen of EVs, permitting efficient transport to tumour tissue, increasing therapeutic potency, and reducing adverse effects. However, the cargo loading is often inadequate and refined methods are a prerequisite for successful utilisation of the platform. By systematically evaluating the effect of altered loading parameters for electroporation, such as total number of EVs, drug to EV ratio, buffers, pulse capacitance, and field strength, we were able to distinguish tendencies and correlations. This allowed us to design an optimised electroporation protocol for loading EVs with the chemotherapeutic drug doxorubicin. The loading technique demonstrated improved cargo loading and EV recovery, as well as drug potency, with a 190-fold increased response compared to naked doxorubicin.

Doxorubicin Induced Apoptosis Enhances Monocyte Infiltration and Adverse Cardiac Remodeling in Diabetic Animals

Diabetic cancer patients treated with Doxorubicin (DOX), a potent chemotherapeutic drug induces cardiac toxicity. However, molecular mechanisms of cardiac toxicity in this specific disease progression in patients and animal models are completely unknown. Therefore, we designed a study to understand the effects of doxorubicin induced cardiac toxicity in diabetic animals and involved pathophysiological mechanisms. C57BL/6J mice were divided into DOX and diabetic (STZ) treated four groups; control, STZ, DOX and DOX+STZ. At Day 14, animals were sacrificed, echocardiography was used to examine heart function, heart and blood samples were collected to investigate apoptotic mechanisms (Caspase 3, BAX, Bcl2), inflammation and cardiac remodeling. Our data shows a significant (p<0.05) increase in glucose levels, apoptotic markers, monocyte infiltration at the site of apoptosis and triggered inflammatory immune response (TNF-α and IL-6), in DOX+STZ animals compared to control and experimental groups. We also observed significant (p<0.05) increase in myofibrillar area, fibrosis and significantly decreased (p<0.05) cardiac function in DOX-treated diabetic animals compared with controls. In conclusion, our data suggest that DOX-induces significantly increased apoptosis, fibrosis and structural alterations in diabetic hearts compared to non-diabetic animals.

Study on Role of In-patient Pharmacist in Prescribed Drug Handling, Mixing, Infusing and Spillage Handling of Chemotherapeutic Drug-Cisplatin in a Tertiary Hospital Pharmacy

The in-patient pharmacist in a cancer hospital plays a major role in patient care especially in patient taking chemotherapy and other narrow indexed drugs as a part of cancer treatment. The pharmacist works as one of the members of cancer treatment team along with physician, oncologist, nurse and other medical professionals. An oncology pharmacist has major role in chemotherapeutic drug handling, mixing, infusing and spillage handling in a disciplined manner. In order to get hands on training about ‘‘oncology-pharmacy’’, it is a mandatory novel pharmaceutical department where a hospital pharmacist who works in oncology will have to get training in handling of chemotherapeutic drugs. The pharmacists who are interested in cancer care will involve in various facets cancer care; from chemotherapeutic drug regimen preparation, mixing of dosage regimen, infusing and finally spillage handling. Hence, it is a mandatory criterion for a graduate pharmacist to get hands on training in specialty Centre to take the responsibility as oncology in-patient pharmacist. The inpatient pharmacist can also be a clinical investigator for various clinical trials involving chemotherapeutic medication usage in patients with cancer. Current study shows that an inpatient pharmacist can play a major role in handling, mixing, infusing and spillage handling of chemotherapeutic drugs in a cancer care centre. The pharmacists are also responsible for reducing drug waste, dealing with drug shortages and reducing exposure to hazardous cytotoxic drugs. The current study suggests that the pharmacist in a cancer care hospital should specially be trained for the handling of chemotherapeutic drugs, mixing and infusion, spillage handling and wastage handling in order to provide accurate treatment for patient and to avoid untoward damage to the person who is handling.

Introducing a novel chemotherapeutic drug for the treatment of oral ‎squamous cell carcinoma‎: Silver nanoparticles green-formulated by ‎ ‎Matricaria chamomilla

IntroductionIn the present research, we formulated a modern chemotherapeutic drug by silver nanoparticles ‎‎(AgNPs) containing Matricaria chamomilla aqueous extract for the treatment of oral squamous ‎cell carcinoma.Material and methodsCharacterization of AgNPs was done by UV–Visible Spectroscopy (UV-Vis), Fourier ‎Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), and ‎Field Emission Scanning Electron Microscopy (FE‐SEM). For investigating the antioxidant ‎properties of AgNO3, M. chamomilla, and AgNPs, the DPPH test was used in the presence of ‎butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-oral ‎squamous cell carcinoma effects of AgNO3, M. chamomilla, and AgNPs, MTT assay was used ‎on the HSC-4, Ca9-22, and HSC-3 cell lines. ‎ResultsDPPH test revealed similar antioxidant potentials for M. chamomilla‎, AgNPs, and butylated ‎hydroxytoluene. Silver nanoparticles had very low cell viability and anti-oral squamous cell ‎carcinoma properties dose-dependently against HSC-4, Ca9-22, and HSC-3 cell lines without ‎any cytotoxicity on the normal cell line. The best result of anti-oral squamous cell carcinoma ‎properties of AgNPs against the above cell lines was seen in the case of the HSC-3 cell line. ‎ConclusionsAccording to the above findings, the silver nanoparticles containing M. chamomilla aqueous ‎extract can be administrated in humans for the treatment of several types of oral squamous cell ‎carcinoma. ‎