Surface modified multifaceted nanocarriers for oral non-conventional cancer therapy; synthesis and evaluation.

Inflammatory cells orchestrate tumor niche for the proliferating neoplastic cells, leading to neoangiogenesis, lymphangiogenesis, tumor growth and metastasis. Emergence of severe side effects, multiple drug resistance and associated high cost has rendered conventional chemotherapy less effectual. The aim was to develop a multipurpose, less toxic, more potent and cheaper, oral non-conventional anticancer therapeutic. Cyclooxygenase associated with tumor niche inflammation and proliferative neoplastic cells were targeted synergistically, through anti-inflammatory and anti-proliferative effects of model drug, diclofenac sodium and fluorescent silver nanoparticles (AgNPs), respectively. Drug entrapped AgNPs were surface modified with PVA (for controlling particle size, preferred cellular uptake, evading opsonization and improved dispersion). XRD, FTIR, DSC, TGA, LIBS, particle size and surface plasmon resonance analysis confirmed the efficient drug encapsulation and PVA coating with 62% loading efficiency. In-vitro, the formulation exhibited 1st order release kinetics with sustained and maximal release at slightly acidic conditions (pH 4.5) enabling the potential for passive tumor targeting. Also, nanoparticles showed efficient protein denaturation inhibition potential, hemo-compatibility (<0.8%) and potent anti-cancer activity (P < 0.05) against breast cancer cell line (MCF-7). In-vivo, developed nanoparticles improved pharmacokinetics (2.8 fold increased AUC, 6.9 h t1/2, Cmax = 1.6 ±â€¯0.03 µg/ml, Kel = 0.1) and pharmacodynamics manifested by potent anti-inflammatory, analgesic and anti-pyretic effects (P < 0.05) at 20 fold lower doses. LD50 determination revealed a wide therapeutic window. The study showed promise of synthesized nanomaterials as cheaper, less toxic, hemo-compatible, oral and more potent anti-inflammatory and non-conventional fluorescent anti-cancer agents, vanquishing tumor niche inflammation and repressing proliferation of malignant cells.

Hemostatic strategies for uncontrolled bleeding: A comprehensive update.

Uncontrolled bleeding remains the leading cause of morbidity and mortality across the entire macrocosm. It refers to excessive loss of blood that occurs inside of body, due to unsuccessful platelet plug formation at the injury site. It is not only limited to the battlefield, but remains the second leading cause of death amongst the civilians, as a result of traumatic injury. Startlingly, there are no effective treatments currently available, to cater the issue of internal bleeding, even though early intervention is of utmost significance in minimizing the mortality rates associated with it. The fatal issue of uncontrolled bleeding is ineffectively being dealt with the use of pressure dressings, tourniquet, and surgical procedures. This is not a practical approach in combat arenas or in emergency situations, where the traumatic injury inflicted is deep inside the body, and cannot be addressed externally, by the application of topical dressings. This review focuses on the traditional hemostatic agents that are used to augment the process of hemostasis, such as mineral zeolites, chitosan based products, biologically active agents, anti-fibrinolytics, absorbable agents, and albumin and glutaraldehyde, as well as the micro- and nano-based hemostatic agents such as synthocytes, thromboerythrocytes, thrombosomes, and the synthetic platelets.