Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry for quantitation and molecular stability assessment of insulin entrapped within PLGA nanoparticles

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) was evaluated for both qualitative and quantitative analysis of insulin entrapped within poly(D,L‐lactic‐co‐glycolic acid) nanoparticles. Quantitation was performed by adding an internal standard (arg‐insulin) to defined and unknown sample solutions, in order to reduce point‐to‐point and sample‐to‐sample variability. The ratio of the peak height of insulin to the peak height of arg‐insulin was plotted against the insulin concentration. In this way, an excellent linear relationship was found (R2 > 0.99). This method of quantitation was compared with classical UV spectroscopy and reverse‐phase high‐performance liquid chromatography measurements. All methods provided close final drug loading values for the insulin‐loaded nanoparticle batches tested. Additionally, with respect to molecular stability, covalent insulin dimers were found only at trace levels in those nanoparticles. Compared with other methods, MALDI‐TOF MS is a valuable tool for the characterization of proteins from nanoparticles, because no extensive extraction and complex sampling procedures are required

Pharmacokinetics of a Novel HIV-1 Protease Inhibitor Incorporated into Biodegradable or Enteric Nanoparticles following Intravenous and Oral Administration to Mice

CGP 57813 is a peptidomimetic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease. This lipophilic compound was successfully entrapped into poly(D,L-lactic acid) (PLA) and pH sensitive methacrylic acid copolymers nanoparticles. The intravenous administration to mice of PLA nanoparticles loaded with CGP 57813 resulted in a 2-fold increase of the area under the plasma concentration-time curve, compared to a control solution. An increase in the elimination half-life (from 13 to 61 min) and in the apparent volume of distribution (1.7-3.6 L/kg) was observed for the nanoparticle incorporated compound vs control solution. Following oral administration, only nanoparticles made of the methacrylic acid copolymer soluble at low pH provided sufficient plasma levels of CGP 57813. In vitro, these nanoparticles dissolved completely within 5 min at pH 5.8. PLA nanoparticles, which are insoluble in the gastrointestinal tract, did not provide significant plasma concentrations of CGP 57813. From these observations, one can conclude that the passage of intact PLA nanoparticles across the gastrointestinal mucosa appears to be very low.</p

The Effect of Rural Hospital Closures on Community Economic Health

OBJECTIVE: To examine the effect of rural hospital closures on the local economy. DATA SOURCES: U.S. Census Bureau, OSCAR, Medicare Cost Reports, and surveys of individuals knowledgeable about local hospital closures. STUDY DESIGN: Economic data at the county level for 1990–2000 were combined with information on hospital closures. The study sample was restricted to rural counties experiencing a closure during the sample period. Longitudinal regression methods were used to estimate the effect of hospital closure on per-capita income, unemployment rate, and other community economic measures. Models included both leading and lagged closure terms allowing a preclosure economic downturn as well as time for the closure to be fully realized by the community. DATA COLLECTION: Information on closures was collected by contacting every state hospital association, reconciling information gathered with that contained in the American Hospital Association file and OIG reports. PRINCIPAL FINDINGS: Results indicate that the closure of the sole hospital in the community reduces per-capita income by $703 (p<0.05) or 4 percent (p<0.05) and increases the unemployment rate by 1.6 percentage points (p<0.01). Closures in communities with alternative sources of hospital care had no long-term economic impact, although income decreased for 2 years following the closure. CONCLUSIONS: The local economic effects of a hospital closure should be considered when regulations that affect hospitals' financial well-being are designed or changed