Hollow mesoporous silica nanoparticles for intracellular delivery of fluorescent dye

In this study, hollow mesoporous silica nanoparticles (HMSNs) were synthesized using the sol-gel/emulsion approach and its potential application in drug delivery was assessed. The HMSNs were characterized, by transmission electron microscopy (TEM), Scanning Electron Microscopy (SEM), nitrogen adsorption/desorption and Brunauer-Emmett-Teller (BET), to have a mesoporous layer on its surface, with an average pore diameter of about 2 nm and a surface area of 880 m2/g. Fluorescein isothiocyanate (FITC) loaded into these HMSNs was used as a model platform to assess its efficacy as a drug delivery tool. Its release kinetic study revealed a sequential release of FITC from the HMSNs for over a period of one week when soaked in inorganic solution, while a burst release kinetic of the dye was observed just within a few hours of soaking in organic solution. These FITC-loaded HMSNs was also found capable to be internalized by live human cervical cancer cells (HeLa), wherein it was quickly released into the cytoplasm within a short period of time after intracellular uptake. We envision that these HMSNs, with large pores and high efficacy to adsorb chemicals such as the fluorescent dye FITC, could serve as a delivery vehicle for controlled release of chemicals administered into live cells, opening potential to a diverse range of applications including drug storage and release as well as metabolic manipulation of cells

Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response. Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. Clinical trial registered with www.clinicaltrials.gov (NCT01560624)