Minimally Invasive Delivery Technologies for Improved Delivery of Therapeutic Proteinsand Vaccines

摘要

In the last few years there has been a tremendousgrowth in the market size of the biotechnologyindustry. Therapeutic proteins and vaccines from thisindustry sector sold approximately $60 billion insales in 2004, with 20% of the top 100 selling drugsbeing derived from the biotechnology industry.Today, the vast majority of biological agents andvaccines are administered by intravenous,subcutaneous or intramuscular injection routes.However, as markets become increasingly crowded,particularly with regards to certain therapeutic areas,marketers are becoming more interested in usingnovel delivery devices to improve patient complianceand to help differentiate drug or vaccine products.Many companies are investigating the use of thetransdermal route as a means of deliveringbiological macromolecules into the systemiccirculation. Unfortunately large hydrophilic moleculessuch as proteins and vaccines are unable totraverse intact skin to elicit therapeutic effects.Consequently, a number of minimally invasivetechniques have been employed to overcome theskin barrier and deposit large proteins and vaccinesinto the outermost layers of the skin. Examples ofsuch techniques are needle free jet injection,ultrasound, radiofrequency and thermal ablation,microneedle and minineedle delivery.We have observed in pre-clinical and clinical studiesthat the systemic pharmacokinetics of varioustherapeutic proteins can be controlled by delivery tospecific skin depths1. For example, shallow injectioninto the upper part of the dermis may result in anincreased rate and extent of systemic uptakewhereas delivery to deeper dermal spaces mayproduce plasma profiles that are similar to thoseseen after subcutaneous injection.For vaccines, we have demonstrated that minimallyinvasive delivery to the epidermis and dermisdelivery increases targeting to keyimmunomodulatory cells such as dermal dendriticcells and epidermal Langerhan's cells resulting inenhanced immunogenicity2,3. Clinical data, withseveral vaccines, has demonstrated that dermaldelivery can result in antigen dose sparing whencompared to intramuscular delivery4. Using minimally invasive delivery techniques it is hopedthat dermal delivery will boost the efficacy of weaklyimmunogenic vaccines and possibly allow foreffective vaccination in certain populations such asthe elderly.