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EricT · 01-04-2007, 07:13 AM

TALO said he is interested so here goes.These are the simplest and most to the point things I’ve been able to find on a cursory search. I wasn’t going to launch into a full pubmed onslaught. I doubt it encompasses the whole subject but it should provide enough terminology so that people won’t think they can bullshit you (hopefully).

Excerpt (the applicable part) from article here.

New transdermal technologies are being developed that greatly expand the range of molecules that can be delivered transdermally. While it is true that the molecular size and solubility characteristics of biopharmaceuticals, such as proteins, peptides, and carbohydrates, prevent their passage through the skin, which is a quite efficient membrane for preventing transport of macromolecules, and preclude their use within typical passive transdermal systems, newer transdermal technologies are making progress in overcoming this barrier.33,34 Several new transdermal technologies incorporate mechanisms to transiently circumvent the normal barrier function of the skin and to allow the passage of macromolecules.

Two of the better-known technologies are iontophoresis and sonophoresis. Both of these technologies have been known for some years, but the rate of product development has been relatively slow as these technologies have emerged. There is currently only one product approved specifically for iontophoretic delivery, and there are no sonophoretic products on the market. These systems can achieve significant skin permeation enhancement, enabling the delivery of proteins, such as insulin and calcitonin.35,36 They also potentially offer significant improvements in control over the rate of drug delivery, but the resulting systems are more complex than passive transdermal systems, and their adoption, at least early on, is likely to be limited to specific applications. Still, they provide an alternative for macromolecular delivery that did not exist 10 years ago.

A newer and potentially more promising technology for macromolecule delivery is microneedle-enhanced delivery. These systems use an array of tiny needle-like structures to open pores in the stratum corneum and facilitate drug transport. An example of this system, 3M’s Microstructured Transdermal System (MTS), is shown in Figure 4. The structures are small enough that they do not penetrate into the dermis and thus do not reach the nerve endings, so there is no sensation of pain. The structures can be either solid (serving as a pretreatment prior to patch application), solid with drug coated directly on the outside of the needles, or hollow to facilitate fluidic transport through the needles and into the lower epidermis. These systems have been reported to greatly enhance (up to 100,000 fold) the permeation of macromolecules through skin.33

Transdermal delivery of vaccines has also been recently reported.38 In this case, the goal is to deliver the antigen to the immune responsive Langerhans cells within the epidermis rather than to the systemic circulation. Typical antigens are very large proteins, or even whole cells, which have long been considered unsuitable for administration through an intact stratum corneum. However, quite impressive immune response has been observed with extremely large antigens, such as tetanus toxoid when co-administered with an adjuvant.39 Relatively simple skin pretreatments, such as hydration, have been shown to improve the immune response. More recently, microneedle arrays have been used as a simple mechanism to pretreat the skin prior to application of the vaccine.40

Improved methods of drug delivery for biopharmaceuticals are important for two reasons: these drugs represent a rapidly growing portion of new therapeutics, and they are most often given by injection. The skin offers a highly accessible, convenient, and very large surface area point-of-entry for these therapies. Existing small molecule products have proven that transdermal drug delivery is a more patient-friendly and preferred method of administration compared to injection and offers the additional benefit of sustained release. Newer technologies, such as microneedle enhancement, are demonstrating that these benefits can be extended to macromolecules as well.

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Here’s another that mentions some of the same things so I’ll include it as well. Sorry it’s a little long. I’ve lost track of the source but I’ll get it in a bit.

The field of controlled release (CR) and drug delivery is extremely broad and covers many disciplines ranging from formulation science to biology.

CR is the use of formulation components and devices to release a therapeutic at a predictable rate in vivo when administered by an injected or non-injected route. To do this, pharmacist and analyst skills are needed to develop and measure release from the formulation, i.e. a polymer or device construction. An example of CR formulation is the transdermal patch containing fentanyl. The rate of drug release from the system is device-led and in theory, the resulting drug plasma levels reach a constant amount per unit time (zero order). Another example is the six-month implant of biodegradable microspheres of the peptide, leuprolide, for treatment of prostate cancer. These formulations avoid the plasma peak and troughs of traditional injections, thus avoiding side effects and making the medicine more effective and acceptable to patients.

More recently, CR has had to encompass the skills of pharmacology and physiology since the release rates of a drug from a polymer in vitro is not the same as what occurs in vivo . In addition, researchers in CR need to know how drugs cross biological membranes, how they interact with immune cells and how they distribute to different organs. Gene delivery, DNA vaccines, cancer chemotherapy and brain delivery of drugs require drug delivery scientists to get involved in understanding antigen presentation, compartmentalization within cells, how to target drugs to cancer cells and how to take advantage of receptor-mediated uptake into the brain and other organs. While we are only beginning to address some of these major medical needs, there have been significant advances, for example, in conjugating anti-cancer agents to new polymers to give targeted formulations with better pharmacokinetics. Using the tools of molecular biology, we are also starting to discover a raft of new potential targets on cancer cells, the blood brain barrier and in the intestine to which we can specifically aim formulations.

Drug delivery at a simplistic level has been dominated by the theme of non-injected peptide delivery. In the 1980's the oral field was dominated by extended release matrix formulations of calcium channel blockers, such as nifedipine and diltiazem: once released in a consistent fashion in the intestine, they were absorbed. In the 1990s, the new biotech peptide molecules such as erythropoietin (EPO) were approved as injectables and these provided a major challenge for drug delivery. For many years, scientists have been trying to administer these peptides by more convenient routes: oral, nasal, pulmonary and transdermal. Of these, inhaled insulin formulations are now in advanced human trials. Oral delivery of peptides and vaccines remain, however, the Holy Grail and there is renewed effort to combine peptides with novel mucoadhesive polymers and to encapsulate them in nanoparticles. This research is divided between trying to increase intestinal permeability and increasing solubility. In the last 10 years, scientists discovered that nanoparticles have a tendency to favour uptake by immune surveillance systems in the intestine and in the dermis of the skin and this led to an increase in vaccine delivery research with novel antigens and adjuvants. Researchers also surprisingly discovered that nanoparticles and liposomes can gain access to the brain and there is real potential for targeting them to the blood brain barrier with ligands. It is worth noting that 95% of all drugs discovered by companies working on Alzheimer's disease and Parkinsonism and stroke have poor brain penetrating capability.

The device side of drug delivery has advanced significantly. We now have intradermal needle-less delivery systems, which safely bombard formulations into the upper viable part of the skin. These have great potential for mass immunization programmes. We also have a number of advanced transdermal systems in research phase including iontophoresis, sonophoresis and patches with probes. Peptide delivery via the skin is back in vogue, although we will have to make the devices simpler and cheaper.

We have seen real advances in polymer research. Many more chemists are working in drug delivery than before. There is a whole range of new bioadhesive and mucoadhesive polymers being made and they have unique properties that allow increased organ retention. The potential for topical treatment of the eye, mouth and intestine has markedly increased. Such polymers, of which the glucosamine-based chitosan was a pioneer, can lead to increased localization and retention of a conjugated drug. More recently, it was discovered that some new polymers containing polyethylene glycol have innate antibacterial activity.

Overall, controlled release and drug delivery is at an exciting time as we enter a new phase in biology. There are some fantastic potent drugs arising from high throughput screens to treat a range of gene and organ-specific conditions, but most have poor pharmacokinetics and cannot yet be specifically targeted in sufficient localized concentration in vivo. It is our job as drug delivery scientists to use our creative thinking to translate the products of drug discovery to real patient benefit. This is a far loftier goal than converting a three-times a day pill into a once-a-day pill or than simply extending the patent life of a peptide therapeutic.