Advanced drug delivery reviews
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Increasing antimicrobial resistance and multiple resistance have resulted in increasing difficulties in the treatment of bacterial infections. Resistance leads to inappropriate empirical therapy, delay in starting effective treatment, and the use of less effective, more toxic, and more expensive drugs. ⋯ All this has significant direct impact on patients and their families and also secondary effects on the cost effectiveness of healthcare delivery. There is an urgent need to control antimicrobial resistance by improved antibiotic usage and reduction of hospital cross-infection.
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Adv. Drug Deliv. Rev. · Feb 2004
ReviewPhase transformation considerations during process development and manufacture of solid oral dosage forms.
The quality and performance of a solid oral dosage form depends on the choice of the solid phase, the formulation design, and the manufacturing process. The potential for process-induced solid phase transformations must be evaluated during design and development of formulations and manufacturing processes. ⋯ The potential phase transformations associated with common unit operations employed in manufacturing solid oral dosage forms are highlighted. Specific examples are given to illustrate the importance of solid phases, and process-induced phase transitions in formulation and process development.
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Adv. Drug Deliv. Rev. · Aug 2003
ReviewSpinal delivery of analgesics in experimental models of pain and analgesia.
Systemic administration of analgesics can lead to serious adverse side effects compromising therapeutic benefit in some patients. Information coding pain transmits along an afferent neuronal network, the first synapses of which reside principally in the spinal cord. Delivery of compounds to spinal cord, the intended site of action for some analgesics, is potentially a more efficient and precise method for inhibiting the pain signal. ⋯ This is one of the mechanisms by which opioids induce analgesia. The spinal cord is enriched in such molecular targets, the activation of which inhibit the transmission of the pain signal early in the afferent neuronal network. This review describes the pre-clinical models that enable new target discovery and development of novel analgesics for site-directed pain management.
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Breastfeeding is the optimal form of infant feeding for the first months of an infant's life, and the majority of healthy women initiate breastfeeding after the birth of their infant. However, women on medication may default to formula feeding or not taking their drug therapy for fear of exposing their infant to the medication through the breast milk. Although the majority of medications are considered to be compatible with breastfeeding, cases of significant infant toxicity exist, suggesting a case by case risk assessment to be made before the mother initiates breastfeeding or drug therapy. ⋯ Circumventing the ethical constraints, approaches have been proposed to estimate drug excretion into milk from physicochemical characteristics of the drug, which diffuses through the mammary gland epithelia. However, as our understanding on drug transfer mechanisms increases, it has become abundantly clear that carrier-mediated processes are involved with excretion of a number of drugs into milk. This article provides an overview of the benefits of breastfeeding, the effect of medication use during breastfeeding on maternal decisions and infant health, and factors determining infant exposure to medication through the breast milk.
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The existence of pathogenic mutations in beta-APP and the presenilin genes provides strong support for the hypothesis that Abeta production and deposition contribute to the etiology of Alzheimer's disease (AD). The heterogeneous carboxyl termini of Abeta molecules deposited in the hippocampus, cortex and cerebrovasculature of AD patients are generated by gamma-secretase. The gamma-secretase that generates the termini in vivo is a complex of proteins containing presenilin as an integral component. ⋯ The use of potent inhibitors has aided the discovery and characterization of gamma-secretase functions and reinforced the concept that a successful drug must demonstrate selectivity for lowering Abeta without disrupting the function of gamma-secretase targets. The discovery of drugs that can selectively inhibit beta-APP cleavage is an important objective. This review focuses on studies that enhance our understanding of the effects of inhibiting gamma-secretase and provide direction for developing effective and selective gamma-secretase inhibitors as drugs to treat AD.