Have you ever forgotten to take your daily pills at the right time? Or missed one altogether? Although important, forgetfulness is not the only problem with drug delivery. Traditionally, most drugs are delivered by oral or intravenous means, which can lead to high concentrations of drugs in the bloodstream with concomitant toxic side effects, and yet only a small percentage of the drug actually reaches the target area. An ideal drug delivery system would maintain optimum therapeutic concentrations of the drug in the target tissue, with minimum fluctuation and allow reproducible release of the drug for long periods of time. In a study published in the November issue of Nature Materials, Langer and colleagues from MIT report a biodegradable drug delivery system with the potential to release pulses of different drugs at various intervals after implantation by using materials of different molecular masses for the membranes covering the drug-containing reservoirs.

The microchip device, made from a degradable polymer, was designed to achieve multi-pulse drug release over periods of several months, without requiring a stimulus to trigger the drug release. Reservoirs machined through a polymer disc were blocked on one side with a layer of degradable polyester tape, loaded with the drug to be released and then sealed with degradable polymeric membranes. Drugs could be released at defined times on the basis of the characteristics of the reservoir membranes. The material used, the molecular mass and the thickness all contribute to the degradation rate of the membrane, and therefore the rate of drug release. The devices were about 11.9 mm in diameter and about 500 μm thick.

Proof-of-principle studies were conducted in vitro with microchips made from poly(L-lactic acid) (PLLA) that used poly(lactic-co-glycolic acid) (PLGA) reservoir membranes of various molecular masses to control the release of test chemicals dextran, heparin and human growth hormone. A 50/50 ratio of lactic acid/glycolic acid was chosen for the membrane as this provides a degradation time of a few weeks to months. In addition, a range of PLGA molecular masses — 4,400, 11,000, 28,000 and 64,000 — were chosen. The results showed four clear pulses of drug over a two-month period as each of the reservoir membranes sequentially degraded and opened. It seems that the driving force for the opening of the membranes comes from water uptake and swelling of the polymer, which is counterbalanced by the mechanical strength of the polymer. Materials with higher molecular masses retain their mechanical strength for longer periods, leading to drug release at later times.

By varying the size and polymer composition of the microchip, the number and volume of the reservoirs, and the composition of the membranes, these devices could offer the opportunity to tailor specific release times of chemicals, as well as enabling the construction of complex release profiles that provide both pulsatile and continuous release of different drugs or chemicals.