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Devices and methods are provided for transmucosal drug delivery. The transmucosal drug delivery device may include a housing configured for intralumenal deployment, such as intravaginally, into a human or animal subject; a drug-dispensing portion which contains at least one drug, the drug-dispensing portion being configured to dispense the drug from the housing by positive displacement; and a permeability enhancer-dispensing portion configured to release or generate a permeability enhancing substance to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time while intralumenally deployed in the human or animal subject. The device may be operable to dispense the drug from the housing to a region of the mucosal barrier disrupted by the permeability enhancing substance.