IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery

Dissolving microneedles are an attractive approach for non-invasive delivery of drugs via the skin, particularly when the doses are in the microgram or low-milligram range. The aim of the study was to develop hyaluronan-based, monoclonal IgG-loaded microneedles for intradermal delivery enabling efficient penetration and rapid dissolution in the skin while preserving protein stability. Microscopic analysis showed successful preparation of sharp microneedles with the tip length of ~ 280 μm and with up to 10% (w/w) of IgG content. The water content of the microneedles was ~ 12% and was not affected by the protein content. The protein distribution was uniform within microneedle tips and individual arrays but some array-to-array variation of IgG level within a single preparation batch was detected. After dissolution of microneedle arrays in PBS, > 80% of protein was recovered and no conformational changes were detected by fluorescence spectroscopy. At submicron level, only weak and reversible interaction between HA and IgG was found by asymmetric flow field flow fractionation analysis after the dissolution of prepared microneedles. Although, the formation of insoluble micron-size particles was detected by flow imaging microscopy the IgG amount incorporated into these particles was negligible (Drug Delivery Technolog

Longitudinal course of extrinsic allergic alveolitis in pigeon breeders.

The purpose of this study was to assess the longitudinal course of pigeon breeders' disease by evaluating 24 patients with the acute form of the disease 10 years after their original diagnosis. Twenty one patients attended for clinical assessment, pulmonary function studies, chest radiography, and antibody measurement. Eighteen had continued to keep pigeons, emphasising their commitment to the hobby. Despite continued antigen exposure pigeon related symptoms had improved in most patients and only five still had troublesome symptoms. Four patients had residual abnormalities of pulmonary function or chest radiographs and three had chronic bronchitis. Fanciers had attempted to regulate their exposure to the birds by use of masks and by spending less time in their lofts but this is an unlikely explanation for the benign course of their disease, as levels of antibody to pigeon gammaglobulin remained high, suggesting that appreciable antigen exposure was still occurring. In most cases a state of equilibrium between host and antigen appeared to have developed. This observation has implications for the clinical management and understanding of the nature of the disease

Pulmonary sarcoidosis with a diffuse ground glass pattern on the chest radiograph.

BACKGROUND--Several chest radiographic abnormalities have been described in pulmonary sarcoidosis, but a diffuse ground glass pattern is extremely rare. METHODS--The chest radiographs of more than 1600 patients with sarcoidosis evaluated in our service between 1976 and 1991 were reviewed to determine the prevalence of this pattern on chest radiography at presentation, and to assess the clinical characteristics of these patients. RESULTS--Ten patients (0.6%) were identified with diffuse ground glass abnormalities on the chest radiography (eight men); all had associated hilar or mediastinal adenopathy. All patients were white and nine were smokers or former smokers. Nine patients were symptomatic and six had inspiratory crackles on physical examination. As a group these patients were remarkable for the frequency and severity of physiological abnormalities and the presence of various findings typically associated with "active" disease. Nine patients were followed for more than three years. All were treated with oral corticosteroids because of significant symptoms or physiological abnormalities, or both. Symptoms and radiological abnormalities disappeared or improved in all patients, but recurred in a high proportion when steroids were tapered or discontinued. By December 1992 only three patients had been withdrawn from treatment. CONCLUSIONS--A diffuse ground glass pattern on the chest radiograph is unusual in patients with sarcoidosis and may occur more commonly in white subjects and cigarette smokers. Its presence suggests the existence of active disease of recent onset likely to require long term treatment with corticosteroids