Cetuximab-conjugated PLGA nanoparticles as a prospective targeting therapeutics for non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers diagnosed worldwide, yet managing it is still challenging. The epidermal growth factor receptor (EGFR) exhibits aberrant signalling in a wide range of human cancers, and it is reported to overexpress in most NSCLC cases. The monoclonal antibody [Cetuximab (Cet)] was conjugated onto the surface of the poly (lactide-co-glycolide) (PLGA) nanoparticles which were loaded with docetaxel (DTX) for the development of targeted therapy against lung cancer. This site-specific delivery system exhibited an enhanced cellular uptake in lung cancer cells which overexpress EGFR (A549 and NCI-H23). The nanoparticles also showed better therapeutic effectiveness against NSCLC cells, as evidenced by reduced IC50 values, cell cycle arrest at the G2/M phase, and increased apoptosis. The improved efficacy and in vivo tolerance of Cet-DTX NPs were demonstrated in benzo(a)pyrene (BaP)-induced lung cancer mice model. Histopathological analysis showed that intravenous injection of Cet-DTX NP to mice carrying lung cancer greatly reduced tumour development and proliferation. Comparing Cet-DTX NP to free drug and unconjugated nanoparticles, it also had negligible side effects and improved survival rates. Therefore, Cet-DTX NPs present a promising active targeting carrier for lung tumour-NSCLC-selective treatment.

MicroRNAs as Potential Diagnostic New Biomarkers in Diagnosis of Sepsis in Pediatric Patients.

Background: Sepsis is one of the most common causes of multiorgan failure. Sepsis requires the presence of infection with a resultant systemic inflammatory state. Organ dysfunction occurs from the combination of the two processes. Sepsis is the main cause of mortality at intensive care units, with 30-50% mortality rate for all septic episodes. MicroRNA (miRNA) profile data could be beneficial as a specific diagnostic biomarker for sepsis and systemic inflammatory response syndrome (SIRS). Methods: Expression of miRNAs -122, -181b, -223 and -146a levels were assayed by quantitative real time polymerase chain reaction (qRT-PCR) in a prospective case control study, where forty septic cases were compared to 40 healthy controls of matched age and gender. Results: miRNAs -122 and -181b were significantly upregulated during early septic conditions, indicating that they could be sensitive and specific biomarkers for diagnosing sepsis. miRNA-223 and miRNA-146a could also represent highly specific and sensitive diagnostic biomarkers, as they were found to be significantly down-regulated. Serum levels of miRNA-223 could be used to predict poor prognosis with 70% sensitivity and 75% specificity, whereas the other three miRNAs could not predict prognosis. Conclusion: Our study shows that all tested miRNAs can be used for early detection of sepsis, with miRNA-223 being predictive of mortality, hence preventing multi-organ failure and reducing mortality, and predicting poor outcomes, thereby assisting in early categorization of ICU patients for rapid appropriate treatment and medico legal aspects.

Therapeutic potential of andrographolide-loaded nanoparticles on a murine asthma model.

Corticosteroids commonly prescribed in asthma show several side-effects. Relatively non-toxic andrographolide (AG) has an anti-asthmatic potential. But its poor bioavailability and short plasma half-life constrain its efficacy. To overcome them, we encapsulated AG in nanoparticle (AGNP) and evaluated AGNP for anti-asthmatic efficacy on murine asthma model by oral/pulmonary delivery. AGNP had 5.47% drug loading with a sustained drug release in vitro. Plasma and lung pharmacokinetic data showed predominantly improved AG-bioavailability upon AGNP administered orally/by pulmonary route. Cell numbers, IL-4, IL-5, and IL-13 levels in broncho-alveolar lavage fluid and serum IgE content were reduced significantly after administration of AGNP compared to free-AG treatment. AGNP-mediated suppression of NF-κß was predominantly more compared to free-AG. Further, pulmonary route showed better therapeutic performance. In conclusion, AGNP effectively controlled mild and severe asthma and the pulmonary administration of AGNP was more efficacious than the oral route.

Apigenin loaded nanoparticle delayed development of hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer related death globally. Apigenin, a dietary flavonoid, possesses anti-tumor activity against HCC cells in-vitro. Development, physicochemical characterization of apigenin loaded nanoparticles (ApNp), biodistribution pattern and pharmacokinetic parameters of apigenin upon intravenous administration of ApNp, and effect of ApNp treatment in rats with HCC were investigated. Apigenin loaded nanoparticles had a sustained drug release pattern and successfully reached the hepatic cancer cells in-vitro as well as in liver of carcinogenic animals. ApNp predominantly delayed the progress of HCC in chemical induced hepatocarcinogenesis in rats. Quantification of apigenin by liquid chromatography-mass spectroscopy (LC-MS/MS) showed that apigenin availability significantly increased in blood and liver upon ApNp treatment. Apigenin loaded nanoparticle delivery substantially controlled the severity of hepatocellular carcinoma and could be a future hope for lingering the survival in hepatic cancer patients.