At a fundamental level, protein adsorption to a synthetic surface must be strongly influenced by the interaction between the peptide residues presented by the protein's surface (primary protein structure) and the functional groups presented by the synthetic surface. In this study, semi-empirical molecular modeling was used along with experimental wetting data to theoretically approach protein adsorption at this primary structural level. Changes in enthalpy, entropy, and Gibbs free energy were calculated as a function of residue-surface separation distance for the adsorption of individual hydrophobic peptide residues (valine, leucine, phenylalanine) on alkanethiol self-assembled monolayers on gold [Au-S(CH(2))(15)-X; X = CH(3), OH, NH(3)(+), COO(-)]. The results predict that the adsorption of each type of hydrophobic residue is energetically favorable and entropy dominated on a methyl-terminated hydrophobic surface, energetically unfavorable and enthalpy dominated on a hydroxyl-terminated neutral hydrophilic surface, and very slightly favorable to unfavorable and enthalpy dominated on charged surfaces. These theoretical results provide a basis for understanding some of the fundamental effects governing protein adsorption to synthetic surfaces. This level of understanding is needed for the proactive design of surfaces to control protein adsorption and subsequent cellular response for both implant and tissue engineering applications.

An implantable radiation dosimeter for use with external beam therapy has been developed and tested both in vitro and in canines. The device uses a MOSFET dosimeter and is polled telemetrically every day during the course of therapy. The device is designed for permanent implantation and also acts as a radiographic fiducial marker. Ten dogs (companion animals) that presented with spontaneous, malignant tumors were enrolled in the study and received an implant in the tumor CTV. Three dogs received an additional implant in collateral normal tissue. Radiation therapy plans were created for the animals and they were treated with roughly 300 cGy daily fractions until completion of the prescribed cumulative dose. The primary endpoints of the study were to record any adverse events due to sensor placement and to monitor any movement away from the point of placement. No adverse events were recorded. Unacceptable device migration was experienced in two subjects and a retention mechanism was developed to prevent movement in the future. Daily dose readings were successfully acquired in all subjects. A rigorous in vitro calibration methodology has been developed to ensure that the implanted devices maintain an accuracy of +/-3.5% relative to an ionization chamber standard. The authors believe that an implantable radiation dosimeter is a practical and powerful tool that fosters individualized patient QA on a daily basis.

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Rapid uptake previously demonstrated by intradermal (ID) drug administration indicates compound delivery within the dermis may have clinical and pharmacological advantages for certain drug therapies. This study is the first clinical trial to evaluate continuous microneedle-based drug infusion, device wearability, and intradermal microneedle insulin kinetics over a multi-day (72 h) wear period. This was a single center, open-label, two-period crossover study in T1DM patients on continuous subcutaneous insulin infusion (CSII). Patients received treatment during interventional visits: one SC and one ID basal/bolus infusion of insulin aspart (NovoRapid® U-100) administered over 3 days in a randomized order. Twenty-eight patients were randomized and exposed to trial product, and 23 completed the study. Bolus insulin infusions were given prior to standardized breakfast and lunch test meals on each of the three treatment days. Blood samples were drawn at predefined time points for measurements of insulin aspart and blood glucose in serum. The primary endpoint insulin Tmax demonstrated that ID bolus infusion was associated with a significantly shorter Tmax with statistically significantly smaller intra-subject variability, compared to SC infusion, and this difference was maintained over three treatment days. Analyses of secondary PK endpoints corresponded with the primary endpoint findings. Postprandial glycemic response was significantly less pronounced after ID bolus: For most endpoints ID vs. SC, differences were statistically significant within the 0–1.5 or 0–2 h time period. Intradermal delivery of insulin is a viable delivery route alternative providing reduced time for insulin absorption with less intra-subject variability and lower glycemic response.

Background: Limited published data exists quantifying the influence of human factors (HF) and pen needle (PN) design on delivery outcomes of pen injection systems. This preclinical in vivo study examines the impact of PN hub design and applied force against the skin during injection on needle penetration depth (NPD). Method: To precisely locate injection depth, PN injections (20 µl; 2 IU, U-100 volume equivalent) of iodinated contrast agent were administered to the flank of Yorkshire swine across a range of clinically relevant application forces against the skin (0.25, 0.75, 1.25, and 2.0 lbf). The NPD, representing in vivo needle tip depth in SC tissue, from four 32 G × 4 mm PN devices (BD Nano™ 2nd Gen and three commercial posted-hub PN devices; n = 75/device/force, 1200 total) was measured by fluoroscopic imaging of the resulting depot. Results: The reengineered hub design more closely achieved the 4 mm target NPD with significantly less variability (P = .006) than commercial posted-hub PN devices across the range of applied injection forces. Calculations of IM (intramuscular) injection risk completed through in silico probability model, using NPD and average human tissue thickness measurements, displayed a commensurate reduction (~2-8x) compared to conventional PN hub designs. Conclusions: Quantifiable differences in injection depth were observed between identical labeled length PN devices indicating that hub design features, coupled with aspects of variable injection technique, may influence injection depth accuracy and consistency. The reengineered hub design may reduce the impact of unintended individual technique differences by improving target injection depth consistency and reducing IM injection potential.