Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety

Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight <500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN.

Experiences with mephedrone pre- and post-legislative controls: Perceptions of safety and sources of supply

Background: Drug scenes within several countries have changed in recent years to incorporate a range of licit psychoactive products, collectively known as “legal highs.” Hundreds of different legal high products have been described in the literature. Many of these products contain synthetic stimulants that allegedly
“mirror” the effects of some illicit drugs. In 2009–2010, growing concern by the UK and Irish governments focused on mephedrone, a synthetic stimulant that had become embedded within several drug scenes in Britain and Ireland. In April 2010, mephedrone and related cathinone derivatives were banned under
the UK’s Misuse of Drugs Act 1971. Setting aside “worse case scenarios” that have been portrayed by UK and Irish media, little is known about mephedrone use from the consumer’s perspective. The purpose of this paper was to (1) explore respondents’ experiences with mephedrone, (2) examine users’ perceptions
about the safety of mephedrone, and primarily to (3) examine sources of mephedrone supply during the pre- and post-ban periods.
Methods: Semi-structured interviews were conducted with 23 adults who had used mephedrone during 2009–2010. Data collection occurred in May and June 2010, following the ban on mephedrone. A total of 20/23 respondents had used mephedrone during the post-ban period, and the vast majority had prior
experience with ecstasy or cocaine. Respondents’ ages ranged from 19 to 51, approximately half of the sample were female and the majority (19 of 23) were employed in full- or part-time work.
Results: Most respondents reported positive experiences with mephedrone, and for some, the substance emerged as a drug of choice. None of the respondents reported that the once-legal status of mephedrone implied that it was safe to use. Very few respondents reported purchasing mephedrone from street-based
or on-line headshops during the pre-ban period, and these decisions were guided in part by respondents’ attempts to avoid “drug user” identities. Most respondents purchased or obtained mephedrone from friends or dealers, and mephedrone was widely available during the 10-week period following the ban. Respondents reported a greater reliance on dealers and a change in mephedrone packaging following the criminalisation of mephedrone.
Conclusion: The findings are discussed in the context of what appears to be a rapidly changing mephedrone market. We discuss the possible implications of criminalising mephedrone, including the potential displacement effects and the development of an illicit market.