This microneedle pill may be used for local delivery of biological drugs via oral administration. It may be used for improving and enhancing the delivery of bioactive substances, such as biologics (e.g. peptides and monoclonal antibodies), to gastrointestinal mucosa for increased bioavailability. Furthermore, the microneedle pill will enable oral administration of therapeutics that are sensitive to the conditions of the GI tract, by “injecting” the drug directly into the GI wall tissue. The needles are coated and cannot be felt by the patient. This system has been tested in vitro and in vivo.
The microneedle pill is aimed at improving the delivery of orally-administered drugs by enhancing the intestinal permeability. It may improve delivery to the GI tract via the mechanical micro-disruption of the gastrointestinal mucosa by the microneedles. It may also be used for systemic delivery by enhancing the uptake of the substance into the vasculature of an organism and via the micro-disruption of gastrointestinal mucosa for increased bioavailability.
The inventors have developed a pill coated with microneedles and a reservoir. Delivery occurs directly from the internal core of the pill to the target tissue. The pill will be capable of selective delivery at different levels of the GI tract by covering microneedles with selective bio-adhesive pH-sensitive coatings. Such selectivity is of interest given the different environments encountered along the GI tract which vary according to pH, protease content, bacterial content and mucosal characteristics. Such selective targeting is attractive as different disease processes may affect different portions of the GI tract.
The microneedles can be made to remain on the shell of the capsule or to release once anchored into the surrounding tissue. In the latter case, the microneedles may be pre-loaded with the drug, enabling its diffusion into the target tissue. Hollow microneedles extending from the pill surface enable micro injection of drug loaded in the inner core of the capsule to the GI tissue, thereby avoiding enzymatic degradation of the drug and improving drug uptake. The pill is coated with a biodegradable sheet that is engineered to degrade and expose the needles at the tissue of interest.
Release of the drug from the pill may be facilitated using an osmotic pump system that is responsive to GI pH or other GI conditions. A portion of the pill wall is coated with a semi-permeable membrane that allows diffusion of fluids into the pill. A polymer or polyelectrolyte then swells in response to the inward flux of water, causing “pumping” of the drug encapsulated in the pill outward through the microneedles. Alternatively, the delivery mechanism may be magnetically triggered externally allowing for both tight control of temporal delivery as well as the ability of localization within the GI tract.
Enhanced intestinal permeability to orally
administered drugs that are currently injected
Micro-disruptions of GI tract facilitate
increased GI bioavailability of drug
pH-selective drug delivery to GI tract allows
for highly specified treatments