Advances in Therapeutic Implications of Inorganic Drug Delivery Nano-Platforms for Cancer.

Numerous nanoparticles drug delivery systems for therapeutic implications in cancer treatment are in preclinical development as conventional chemotherapy has several drawbacks. A chemotherapeutic approach requires high doses of chemotherapeutic agents with low bioavailability, non-specific targeting, and above all, development of multiple drug resistance. In recent years, inorganic nano-drug delivery platforms (NDDPs; with a metal core) have emerged as potential chemotherapeutic systems in oncology. One of the major goals of developing inorganic NDDPs is to effectively address the targeted anti-cancer drug(s) delivery related problems by carrying the therapeutic agents to desired tumors sites. In this current review, we delve into summarizing the recent developments in targeted release of anti-cancer drugs loaded in inorganic NDDPs such as mesoporous silica nanoparticles, carbon nanotubes, layered double hydroxides, superparamagnetic iron oxide nanoparticles and calcium phosphate nanoparticles together with highlighting their therapeutic performance at tumor sites.

Root cause analysis of non-infectious transfusion complications and the lessons learnt.

BACKGROUND: Transfusion of blood and blood products can be associated with hazards which may be at times fatal. Timely reporting of transfusion reactions is imperative for root cause analysis and their prevention in future. METHODS: We retrospectively reviewed the transfusion reactions at our institution during last seven years. The data was retrieved from our computerized blood bank information system and by reviewing the medical charts of patients. The frequency of adverse effects, implicated products, wrong blood transfusion and its outcome were observed. RESULTS AND CONCLUSIONS: During study period (2006-2012), a total of 393,662 blood or blood products were transfused. There were 458 adverse events with an estimated rate of 1.16 per 1000 blood products administered. During 2011-2012, 121 transfusion reactions were reported of 119,921 transfused units. The most common adverse effects were allergic reactions (70 episodes of 121 or 57.8%) followed by febrile non hemolytic transfusion reactions or FNHTR (43 events of 121 or 35.5%). Transfusion associated dyspnea, circulatory overload and transfusion associated lung injury were less frequent. During the study period, 142,066 red cell units were transfused with nine recognized ABO-mismatch transfusions and two fatalities. The computed incidence of ABO-mismatch transfusion was 1 in 15,785 with a mortality rate of 1 in 71,033 units transfused. Etiology included: errors in final bed side check (n=5), blood bank clerical errors (n=3) and mislabeled tube (n=1). A review of these cases prompted hospital transfusion committee for re-enforcing policies and protocols to minimize accidental ABO incompatible transfusions. We concluded that urticaria and FNHTR are the most frequent transfusion reactions in our setting. ABO mismatched blood transfusions are rare but preventable errors and result mainly from clerical imprecisions.

Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery.

Background: Drug delivery systems (DDS) capable of targeting both cell and organelle levels are highly desirable for effective cancer therapy. In this study, we developed a novel enzyme-responsive, multistage-targeted anticancer DDS based on mesoporous silica nanoparticles (MSNs), which possessed both CD44-targeting and mitochondrial-targeting properties. Materials and methods: Triphenylphosphine (TPP), a mitochondria-targeting compound, was grafted onto the surface of MSNs firstly. Then, Doxorubicin (Dox) was encapsulated into the pore of MSNs, followed by capping with tumor-targeting molecules hyaluronic acid (HA) through electrostatic interactions to form the final product consist of Dox loaded, TPP attached, HA capped mesoporous silica nanoparticles (MSN-DPH). Results: Our results suggested that MSN-DPH was preferentially taken up by cancer cells via CD44 receptor-mediated endocytosis. Moreover, MSN-DPH mainly accumulated in mitochondria owing to the mitochondrial-targeting ability of TPP. Degradation of HA by overexpressed HAase facilitated the release of Dox in cancer cells. Thus, MSN-DPH efficiently killed the cancer cells while exhibited much lower cytotoxicity to normal cells. Conclusion: This study demonstrates a promising multistage-targeted DDS for cancer chemotherapy.