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raska � jr, voelkerding k, lehman jm and mannino rj gene perez o, brach g, lastre m, mora theophylline n, del campo j, gil d, zayas c, acevedo r, gonzales d, lopez j, taboada � and solis rl novel adjuvant based on a proteoliposomederived cochleate structure containing native polysaccharide as a pathogenassociated molecular pattern immunol cell biol aerosols as drug carriers n renee labiris, andrew p bosco and myrna theophylline b dolovich introduction as the end organ for the treatment of local theophylline diseases or as the route of administration for systemic therapies, the lung theophylline is a very attractive target for drug delivery table the lung provides direct access to the site of disease for the treatment of respiratory illness, theophylline without the inefficiencies and unwanted effects of systemic drug delivery in addition, it theophylline provides an enormous surface area and a relatively low enzymatic environment for theophylline the absorption of drugs to treat systemic diseases table inhaled medications have been available for many years for the treatment of lung diseases inhalational delivery has been widely accepted as being the optimal route of administration of first theophylline line therapy for asthmatic and chronic obstructive pulmonary diseases drug formulation plays an important role in producing an effective inhalable medication in addition to being pharmacologically active, it is important that a drug be efficiently delivered into theophylline the lungs, to the appropriate site of action and remain in the lungs theophylline until the desired pharmacological effect occurs a drug designed to treat a systemic disease, such as insulin for diabetes, must be deposited in the lung theophylline periphery to ensure maximum systemic bioavailability for gene therapy, anti cancer or anti infective treatment, cellular uptake and prolonged residence in the lungs of the theophylline drug may be required to obtain the optimal therapeutic effect thus, a theophylline formulation that is retained in the lungs for the desired length of time theophylline and avoids the clearance mechanisms of the lung may be necessary the human lung contains airways and approximately million alveoli with a surface area of theophylline m, equivalent to that of a tennis court as a major port theophylline of table advantages of pulmonary delivery of drugs to treat respiratory and systemic disease treatment of respiratory diseasestreatment of systemic diseases deliver high drug concentrations theophylline directly to the disease site minimizes risk of systemic side effects rapid clinical theophylline response bypass the barriers to therapeutic efficacy, such as poor gastrointestinal absorption theophylline and firstpass metabolism in the liver achieve a similar or superior therapeutic theophylline effect at a fraction of the systemic dose for example, oral salbutamol mg theophylline is therapeutically equivalent to xg by mdi a noninvasive needlefree delivery system theophylline suitable for a wide range of substances from small molecules to very large proteins enormous absorptive surface area m and a highly permeable membrane to theophylline fim thickness in the alveolar region large molecules with very low absorption rates can be absorbed in significant quantities the slow mucociliary clearance in the lung periphery results in prolonged residency in prednisone interaction with warfarin the lung a less harsh, low enzymatic environment avoids firstpass metabolism reproducible absorption kinetics pulmonary delivery is independent theophylline of dietary complications, extracellular enzymes and interpatient metabolic differences that affect gastrointestinal absorption theophylline entry, the lung has evolved to prevent the invasion of unwanted airborne theophylline particles from entering into the body airway geometry, humidity, mucociliary clearance and alveolar theophylline macrophages play a vital role in maintaining the sterility of the lung, and consequently, they can be barriers to the therapeutic effectiveness of inhaled medications the size of the drug particle can play an important role in theophylline avoiding the physiological barriers of the lung and targeting to the appropriate lung theophylline region fig nanoparticles are solid colloidal particles ranging in size from to nm studies have demonstrated that they are taken up by macrophages, cancer cells, theophylline and epithelial cells their small size ensures the particles containing the active theophylline pharmacological ingredient will reach the alveolar regions however, the use of an aerosol theophylline delivery system that generates nanosized particles for inhalation, places these particles at risk of being exhaled, leaving very few drug particles to be deposited in theophylline the periphery of the lung residence time is not long enough for theophylline the particles to be deposited by sedimentation or diffusion aerosols as drug carriers diffusionseemntationinertia!