Core-shell microneedle platform for transdermal and pulsatile drug/vaccine delivery and method of manufacturing the same
A core-shell microneedle system and a method of manufacturing the microneedle system provides a pulsatile drug delivery system which is programmed to release drugs/vaccines at predictable times using biodegradable polymers and with controllable dosages. This microneedle system can be fully embedded into the skin and then release drugs/vaccines as sharp bursts in a timely manner, similar to multiple bolus injections.
1 . A drug delivery system comprising:
an assembly including
a substrate, and
a plurality of microneedles extending from the substrate, each microneedle including:
a shell including a biodegradable polymer, said shell having a tapered shape from a distal tip to a proximal base having a diameter larger than the distal tip,
a core including a mixture of a therapeutic agent and a polymeric carrier,
and
a cap including a biodegradable polymer, the cap bonded to the base of the shell and enclosing the core within the shell, said cap and shell not including any therapeutic agent, and
said assembly comprising:
a water-soluble polymer layer between the cap and the substrate, said water-soluble polymer layer connecting the microneedles to the substrate with the tips of the microneedles directed away from the substrate,
wherein the water-soluble polymer layer is configured to dissolve to release the microneedles from the substrate when the microneedles are inserted into the skin of a patient, leaving the microneedles embedded in the skin where the cap and shell of each of the plurality of microneedles degrade at a predetermined time to release the therapeutic agent therein into the skin of the patient.
2 . The drug delivery system of claim 1 , wherein the biodegradable polymer of the shell includes Poly(D,L-lactide-co-glycolide) (“PLGA”) or poly-lactide acid (“PLA”).
3 . The drug delivery system of claim 2 , wherein the cap includes PLGA or PLA.
4 . The drug delivery system of claim 1 , wherein the polymeric carrier is Polyvinylpyrrolidone, Polyvinyl alcohol, Polyethylene glycol, or (Hydroxypropyl)methyl cellulose.
5 . The drug delivery system of claim 1 , wherein the cap and shell of a first subset of the plurality of microneedles is selected to degrade at a first time to release the therapeutic agent therein into skin of a patient, and wherein the cap and shell of a second subset of the plurality of microneedles is selected to degrade at a second time different from the first time to release the therapeutic agent therein into the skin of the patient.
6 . The drug delivery system of claim 1 , wherein the therapeutic agent is a vaccine.
7 . The drug delivery system of claim 6 , wherein the cap and shell of a first subset of the plurality of microneedles is selected to degrade at a first time to release a first dose of the vaccine therein into skin of a patient, and wherein the cap and shell of a second subset of the plurality of microneedles is selected to degrade at a second time different from said first time to release a second dose of the vaccine therein into the skin of the patient.
8 . The drug delivery system of claim 1 , wherein the therapeutic agent is insulin or a growth hormone.
9 . The drug delivery system of claim 1 , wherein the therapeutic agent treats pain or allergy symptoms of a patient.
10 . The drug delivery system of claim 1 , wherein the core of at least one of the microneedles includes a maximum diameter of 200 μm and a maximum height of 300 μm.
11 . The drug delivery system of claim 10 , wherein at least one of the microneedles in the plurality of microneedles includes a maximum height of 600 μm.