Polymer microneedles for controlled-release drug delivery.
OBJECTIVE
As an alternative to hypodermic injection or implantation of controlled-release systems, this study designed and evaluated biodegradable polymer microneedles that encapsulate drug for controlled release in skin and are suitable for self-administration by patients.


METHODS
Arrays of microneedles were fabricated out of poly-lactide-co-glycolide using a mold-based technique to encapsulate model drugs--calcein and bovine serum albumin (BSA)--either as a single encapsulation within the needle matrix or as a double encapsulation, by first encapsulating the drug within carboxymethylcellulose or poly-L: -lactide microparticles and then encapsulating drug-loaded microparticles within needles.


RESULTS
By measuring failure force over a range of conditions, poly-lactide-co-glycolide microneedles were shown to exhibit sufficient mechanical strength to insert into human skin. Microneedles were also shown to encapsulate drug at mass fractions up to 10% and to release encapsulated compounds within human cadaver skin. In vitro release of calcein and BSA from three different encapsulation formulations was measured over time and was shown to be controlled by the encapsulation method to achieve release kinetics ranging from hours to months. Release was modeled using the Higuchi equation with good agreement (r2 > or = 0.90). After microneedle fabrication at elevated temperature, up to 90% of encapsulated BSA remained in its native state, as determined by measuring effects on primary, secondary, and tertiary protein structure.


CONCLUSIONS
Biodegradable polymer microneedles can encapsulate drug to provide controlled-release delivery in skin for hours to months.
Park
Jung-Hwan
JH
Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Allen
Mark G
MG
Prausnitz
Mark R
MR
D001672:Biocompatible Materials / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D016503:Drug Delivery Systems; D004355:Drug Stability; D004867:Equipment Design; D006801:Humans; D007271:Injections, Intradermal / Q000295:instrumentation; D019344:Lactic Acid / Q000737:chemistry; D008845:Microinjections / Q000295:instrumentation*; D009339:Needles; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012646:Self Administration / Q000295:instrumentation; D012867:Skin / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid