Advanced drug delivery reviews
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Adv. Drug Deliv. Rev. · Oct 2006
ReviewClinical perspectives on pulmonary systemic and macromolecular delivery.
The large epithelial surface area, the high organ vascularization, the thin nature of the alveolar epithelium and the immense capacity for solute exchange are factors that led the lung to serve as an ideal administration route for the application of drugs for treatment of systemic disorders. However, the deposition behaviour of aerosol particles in the respiratory tract depends on a number of physical (e.g. properties of the particle), chemical (e.g. properties of the drug) and physiological (e.g. breathing pattern, pulmonary diseases) factors. If these are not considered, it will not be possible to deposit a reproducible and sufficient amount of drug in a predefined lung region by means of aerosol inhalation. ⋯ However, over the last 20 years, there has been considerable progress in aerosol research and in the understanding of the underlying mechanisms of particle inhalation and pulmonary particle deposition. As a consequence, an increasing number of studies have been performed for the lung administration of drugs using a variety of different inhalation techniques. This review describes the physical and in part some of the physiological requirements that need to be considered for the optimization of pulmonary drug delivery to target certain lung regions.
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Pulmonary opioid delivery, on the basis of the fact that small molecular entities can be rapidly and completely absorbed from the peripheral lung, poses a unique opportunity for the treatment of severe (breakthrough) pain, which currently is treated with intravenous therapy. Early clinical studies involving inhaled opioids were focused on treatment of dyspnoea and not pain management, but they showed that inhalation of various opioid compounds is safe, even in severely ill patients. ⋯ This review will summarize recent literature on the pharmacokinetics and pharmacodynamics of inhaled opioids and will discuss safety and efficacy in comparison to injection and other opioid dosage forms available for pain therapy. Finally, regulatory considerations will be discussed towards the approval of this new delivery paradigm for opioid drugs.
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Osteoarthritis (OA), the syndrome of joint pain and dysfunction caused by joint degeneration, affects more people than any other joint disease. In most instances joint degeneration develops in the absence of an identifiable cause, but increasing age, excessive joint loading, and joint abnormalities and insults increase the risk of OA. Articular surface contact stress that causes tissue damage and compromises that ability of chondrocytes to maintain and restore the tissue has an important role in the development of joint degeneration Current methods of attempting to restore an articular surface in osteoarthritic joints include penetrating subchondral bone, altering joint loading, osteotomies and insertion of soft tissue grafts. Dramatic advances in the prevention and treatment of OA are likely to stem from better understanding of the role of mechanical forces in the initiation and progression of joint degeneration.
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Deep somatic pain originating in joints and tendons is a major therapeutic challenge. Spontaneous pain and mechanical hypersensitivity can develop as a consequence of sensitization of primary afferents directly involved in the inflammatory process, but also following sensitization of neuronal processing in the spinal cord (central sensitization) or higher centres. ⋯ New targets for analgesic therapy include sensory proteins at the nociceptive nerve endings such as the activating TRPV and ASIC channels, but also inhibitory opioid and cannabinoid receptors. Therapeutic targets are also found among the axonal channels that set membrane potential and modulate discharge frequency such as voltage sensitive sodium channels and various potassium channels.