A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.

With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus CalmetteGué rin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, freeflowing, ''vial-fillable'' powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4°C and 25°C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.aerosolization ͉ bacillus Calmette-Gué rin ͉ spray drying ͉ dry powder ͉ mycobacterium B acillus Calmette-Guérin (BCG), the most widely administered childhood vaccine in the world with 100 million infant administrations annually (1), is presently delivered by needle injection, requires refrigerated storage, and has shown in different parts of the world variable degrees of protection against tuberculosis (TB) ranging from 0% to 80% (2). Given the increasing global burden of TB, its coupling to the HIV/AIDS epidemic, and the emerging problem of drug resistance, there is a clear need for alternatives to the traditional BCG vaccine and current treatment strategies (2, 3). An optimal new vaccine would obviate needle injection, not require refrigerated storage, and provide a safe and more consistent degree of protection.Current commercial BCG vaccine preparations are filled as bacterial suspensions in vials, dried through lyophilization, and stabilized through refrigeration for up to 1 year on the shelf (4). Lyophilization, or freeze-drying, however, is known to produce significant losses of BCG viability after freezing (5). Moreover, lyophilized BCG fails to exhibit satisfactory shelf stability at room temperature, a major liability for transport and distribution, particularly in low-income environments, where the TB epidemic is most seriously concentrated (4, 6). Most importantly for our work, lyophilized BCG does not exhibit a particle form conducive for potential noninjectable delivery, notably through an aerosol route.In the search for a more effective vaccine against TB, spray drying provides an attractive alternative to lyophilization. It is less costly to operate (6), can be scaled up in sterile conditions, avoids cell freezing (7), and has the potential to be inhaled (8). Previous published att...

The preparation and characterization of microparticles produced from a new class of functionalized, biodegradable, comblike graft copolymers is presented. The copolymers are polyester-polyamino acid hybrids, composed of a poly(L-lactic acid-co-L-lysine) (PLAL) backbone, and poly(L-lysine), poly(D,L-alanine) or poly(L-aspartic acid) side chains extending from the lysine residues of PLAL. The microparticles have been characterized with regard to their surface properties, morphology, and size. Thus, electron spectroscopy for chemical analysis data and results of Zeta potential measurements suggest that the polyamino acid side chains tend to concentrate at the surface of the particles. Also, analyses by environmental scanning electron microscopy and confocal scanning laser microscopy indicate that particles carrying poly(lysine) chains have an unusual porous structure, most probably due to the combined effects of the amphiphilic, polyelectrolyte, and chemical nature of the composing copolymer, as well as of the particular preparation technique employed. The capabilities of the microparticles to serve as carriers in controlled drug release and delivery devices were demonstrated by encapsulation and release of rhodamine B, a low molecular weight drug model.