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Dendrimers are an emerging class of nanoscale intracellular drug delivery vehicles. Methylprednisolone (MP) is an important corticosteroid used in the treatment (through inhalation) of lung inflammation associated with asthma. The ability of MP–polyamidoamine (PAMAM) dendrimer conjugate to improve the airway delivery was evaluated in a pulmonary inflammatory murine model that was based on an 11-fold enhancement of eosinophil lung accumulation following five daily inhalation exposures of sensitized mice to the experimental allergen, ovalbumin. MP was successfully conjugated to PAMAM-G4-OH dendrimer yielding 12 MP molecules per dendrimer, and further solubilized in lysine carrier. Five daily trans-nasal treatments with the carrier alone, free MP, and MP–dendrimer at 5 mg kg−1 (on a drug basis) did not induce additional lung inflammation, although free MP decreased baseline phagocytic cell recoveries by airway lavage and tissue collagenase dispersion. MP treatments alone decreased ovalbumin-associated airway and tissue eosinophil recoveries by 71 and 47%, respectively. Equivalent daily MP dosing with MP–dendrimer conjugate further diminished these values, with decreases of 87% and 67%, respectively. These findings demonstrate that conjugation of MP with a dendrimer enhances the ability of MP to decrease allergen-induced inflammation, perhaps by improving drug residence time in the lung. This is supported by the fact that only 24% of a single dose of dendrimer delivered to the peripheral lung is lost over a 3-day period. Therefore, conjugation of drugs to a dendrimer may provide an improved method for retaining drugs within the lung when treating such inflammatory disorders as asthma.

Highly branched, functionalized polymers have potential to act as efficient drug carrier systems. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups. Using ibuprofen as a model drug, we studied the interaction between the drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with --NH2 functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with --OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly forms a complex with PAMAM dendrimers because of the ionic interaction between the --NH2 end groups and the carboxyl group of ibuprofen. On an average, up to 78 molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH2 with 64 end groups. This complex is stable in deionized water and methanol. The in vitro release of ibuprofen from drug-dendrimer complex is appreciably slower compared to pure ibuprofen. The complexed drug enters A549 cells much more rapidly than pure drug suggesting that dendrimers may be able to carry the complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 --OH end groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack of strong interactions between the --OH end groups and the drugs prevents complex formation.

In spite of modern technological advances, ARDS continues to be an important cause of morbidity and mortality from a diverse group of disorders such as sepsis, trauma, and aspiration. ARDS represents a target organ injury resulting from activation of the host's inflammatory cells and uncontrolled liberation of inflammatory mediators. In most instances, therefore, ARDS is a localized manifestation of a widespread onslaught characteristic of SIRS. At this time, there are no proven interventions to prevent ARDS, and the management is mainly supportive. Modulation of the host's inflammatory response seems to hold the most promise for prevention and treatment of ARDS. Such strategies need to be explored with well-controlled clinical trials.

Objective To assess emergency department (ED) utilization and physician preparedness for infants with single ventricle (SV) physiology between stage 1 and stage 2 surgical palliation. Study design Records of infants with SV physiology discharged after stage I palliation between July 2006 and June 2009 were retrospectively reviewed. Next, a cross-sectional survey of registered ED physicians in Michigan was performed. Results Thirty-three of 42 patients (79%) required 65 ED visits, most commonly presenting with respiratory distress (35%). Six patients died in the ED; 35 other visits resulted in hospital admission, 4 requiring urgent surgery or catheterization. Median initial hospital stay in those with ED visits was significantly longer (21 days; IQR, 17-45 days) than those without (12 days; IQR, 5.5-24 days) (P = .032). Three hundred seventy-six of 915 surveyed ED physicians responded. Most (72%) were unsure of the acceptable range of arterial oxygen saturation for these infants, and 58% felt “uncomfortable” or “worried” about their treatment. Despite these concerns, 59% deemed education in SV physiology as low priority. Conclusions Between stages I and II, infants with SV physiology utilized the ED frequently, often with high disease acuity. Most ED physicians surveyed appeared underprepared for these infants. These findings underscore the need for educational efforts aimed at increasing ED preparedness.