Research ArticleDrug Delivery

First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip

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Science Translational Medicine  22 Feb 2012:
Vol. 4, Issue 122, pp. 122ra21
DOI: 10.1126/scitranslmed.3003276
  • Fig. 1

    The microchip-based drug delivery device and overview of study design. (A and B) Microchip-based hPTH(1–34) drug delivery device (54 mm × 31 mm × 11 mm, l × w × h) (A) containing two microchips with 10 reservoirs each (13.0 mm × 5.4 mm × 0.5 mm, l × w × h) (B). (C) Schematic cross section of microchip assembly showing drug releasing from one reservoir. (D) Timeline of study events.

  • Fig. 2

    PK dosing results. (A) Plasma concentration of hPTH(1–34) versus time after release of 40-μg dose from implanted microchip device for the seven study patients. (B) Plasma concentration of hPTH(1–34) versus time after injection of 20- and 40-μg doses of FORSTEO for the seven study patients. The 40-μg doses were administered as two sequential 20-μg injections. (C) Mean plasma concentration of hPTH(1–34) versus time after release of 40-μg dose from the implanted microchip device (n = 7 patients × four doses) and injection of 2 × 20–μg doses of FORSTEO (n = 7 patients × two doses). Data are means ± SD.

  • Fig. 3

    Bone marker and calcium measurements. (A) P1NP and CTX bone marker concentrations in serum before, during, and after implant-mediated drug dosing. The shaded area encloses the 2 weeks during which individual 40-μg doses of hPTH(1–34) were released from the implant once daily. Data are means ± SD (n =7). *P < 0.05 compared to day −12 (screening visit), pairwise t test. (B) Serum calcium levels during dosing from the microchip implant (n = 28) and the 2 × 20–μg injections (n = 14). *P < 0.05 compared to predose calcium levels, pairwise t test. (C) Baseline serum calcium levels over the course of the study (n = 7). The shaded area in (B) and (C) represents range of normal serum calcium values. Data are means ± SD.

  • Fig. 4

    Tissue histology results from a representative patient, MC-0012. (A and B) Two representative macroscopic images of the tissue capsule surrounding the device after explantation. (C to H) Micrographs of the tissue capsule from each patient consisted of three total images from both the dorsal (antenna, toward skin) and the ventral (microchip, toward muscle) sides. Top row, H&E stain; bottom row, Masson’s trichrome stain. (C and D) Cross-section 1 at the microchip and titanium interface (dorsal). (E and F) Cross-section 2 over the microchip (ventral). (G and H) Cross-section 3 over the titanium case (ventral).

  • Table 1

    PK parameters throughout the device dosing period. Data are means ± SD (n = 7).

    DayCmax (ng/ml)Tmax (min)AUC (ng·min/ml)T1/2 (min)
    60410 ± 17544 ± 1344 ± 1066 ± 16
    65426 ± 20949 ± 1044 ± 964 ± 20
    70378 ± 13341 ± 1143 ± 975 ± 27
    84405 ± 15445 ± 1246 ± 676 ± 16
  • Table 2

    Results of PK parameters by patient. (A) Doses delivered by the implant (n = 4). (B) Doses delivered as 2 × 20–μg injections (n = 2). Data are means ± SD.

    PatientCmax (ng/ml)Tmax (min)AUC (ng·min/ml)T1/2 (min)
    A. Implant [hPTH(1–34)]
    MC-0002538 ± 11151 ± 851 ± 251 ± 11
    MC-0003249 ± 4956 ± 836 ± 489 ± 28
    MC-0005598 ± 6732 ± 348 ± 448 ± 7
    MC-0011353 ± 7941 ± 1436 ± 769 ± 4
    MC-0012255 ± 1945 ± 1241 ± 191 ± 8
    MC-0018575 ± 5139 ± 1057 ± 268 ± 5
    MC-0020266 ± 4349 ± 840 ± 372 ± 12
    B. Injection (FORSTEO)
    MC-0002489 ± 12726 ± 626 ± 139 ± 13
    MC-0003335 ± 3925 ± 724 ± 544 ± 5
    MC-0005206 ± 9328 ± 2618 ± 164 ± 19
    MC-0011255 ± 2321 ± 127 ± 977 ± 7
    MC-0012476 ± 5623 ± 437 ± 161 ± 4
    MC-0018770 ± 4311 ± 1741 ± 345 ± 2
    MC-0020273 ± 527 ± 522 ± 149 ± 6
  • Table 3

    Average PK parameters for hPTH(1–34) from the microchip device compared to 2 × 20–μg and single 20-μg FORSTEO injections. Data are means ± SD. ND, not determined.

    Drug, method of deliveryDose (μg)Number of samplesCmax (pg/ml)Tmax (min)AUC0–last (ng·min/ml)T1/2 (min)Reference
    hPTH(1–34), implant4028405 ± 16145 ± 1144 ± 870 ± 20This study
    FORSTEO, injection2 × 2014400 ± 19423 ± 1028 ± 953 ± 15This study
    FORTEO, injection*4034460 (146–875)58 (40–91)46 (17–69)ND(21)
    FORSTEO, injection2014192 ± 5522 ± 614 ± 455 ± 16This study
    FORTEO, injection2022151 ± 5732 ± 1510 ± 490 ± 107(21)

    *Range shown in parentheses.

    Additional Files

    • Supplementary Material for:

      First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip

      Robert Farra,* Norman F. Sheppard Jr., Laura McCabe, Robert M. Neer, James M. Anderson, John T. Santini Jr., Michael J. Cima, Robert Langer

      *To whom correspondence should be addressed. E-mail: rfarra{at}mchips.com

      Published 16 February 2012, Sci. Transl. Med. 4, 122ra21 (2012)
      DOI: 10.1126/scitranslmed.3003276

      This PDF file includes:

      • Fig. S1. Overview of the histological analysis performed on the tissue capsule for each patient.
      • Table S1. Patient history collected at screening visit (day −12).
      • Table S2. Results of routine kidney panel assessment (n = 7 patients).
      • Table S3. Results of routine liver panel assessment (n = 7 patients).
      • Table S4. Survey questions and responses conducted throughout the study.

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