Drug delivery across length scales

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future

Refill Port Identification of Intrathecal Drug Delivery System Devices With a Raised Fill Port

Objectives The aim of this study was to assess the accuracy of the manual identification of the reservoir fill port (RFP) for refill of intrathecal drug delivery systems (IDDSs) with a raised RFP on the pump surface (raised-RFP-IDDSs), and compare this to previously reported data of patients with IDDSs with a recessed RFP (recessed-RFP-IDDSs). Methods Nineteen patients underwent 2 IDDS refills for the treatment of noncancer pain or spasticity. The primary endpoint of this prospective observational study was the deviation between the needle insertion point and the RFP center, quantified by fluoroscopic visualization. A distance surpassing that between the center and the margin of the RFP of 4 mm was considered a clinically relevant deviation. The results were compared with previously reported data of a patient cohort with recessed-RFP-IDDSs, and the differences were tested using Student's t-test. Results The mean deviation from the RFP center was 4.9 mm (standard deviation = 3.7). The RFP identification accuracy deviated more than the clinically relevant difference in 17 out of 35 instances (48.6%). The number of attempts and median procedural time was significantly correlated to the needle deviation. The mean deviations in the raised-RFP-IDDS cohort were consistently lower compared to the recessed-RFP-IDDS cohort (first refill procedure 4.0 vs. 8.5, P <0.001; second procedure 5.9 vs. 8.1, P = 0.074). Conclusion The results of this study suggest that the manual localization of the RFP for raised-RFP-IDDSs is moderately accurate, and more accurate if compared to previously published accuracy of the template-guided technique for recessed-RFP-IDDSs