Hypodermic needles are in widespread use, but patients are unhappy with the pain, anxiety, and difficulty of using them. To increase patient acceptance, smaller needle diameters and lower insertion forces have been shown to reduce the frequency of painful injections. Guided by these observations, fine needles and microneedles have been developed to minimize pain and have found the greatest utility for delivery of vaccines and biopharmaceuticals such as insulin. However, pain reduction must be balanced against limitations of injection depth, volume, and formulations introduced by reduced needle dimensions. In some cases, needle-free delivery methods provide useful alternatives.
HauriAArmstrongGHutinY. The global burden of disease attributable to contaminated injections given in health care settings. Int J STD AIDS. 2004 Jan; 15 (1): 7–16.
3.
LindhWQ. Delmar's comprehensive medical assisting: Administrative and clinical competencies. Albany (NY): Delmar Health Care Publishing; 1998.
4.
KrogerAAtkinsonWMarcuseEPickeringL. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 55 (RR-15). Centers for Disease Control and Prevention, Atlanta, GA; 2006.
5.
SchwartzSHassmanDShelmetJSieversRWeinsteinRLiangJLynessW. A multicenter, open-label, randomized, two-period crossover trial comparing glycemic control, satisfaction, and preference achieved with a 31 gauge × 6 mm needle versus a 29 gauge × 12.7 mm needle in obese patients with diabetes mellitus. Clin Ther. 2004 Oct; 26 (10): 1663–78.
6.
DeaconBAbramowitzJ. Fear of needles and vasovagal reactions among phlebotomy patients. J Anxiety Disord. 2006; 20 (7): 946–60.
7.
HanasR. Reducing injection pain in children and adolescents with diabetes: a review of indwelling catheters. Pediatr Diabetes. 2004 Jun; 5 (2): 102–11.
8.
BerlinIBisserbeJCEiberRBalssaNSachonCBosquetFGrimaldiA. Phobic symptoms, particularly the fear of blood and injury, are associated with poor glycemic control in type I diabetic adults. Diabetes Care. 1997 Feb; 20 (2): 176–8.
9.
Arendt-NielsenLEgekvistHBjerringP. Pain following controlled cutaneous insertion of needles with different diameters. Somatosens Mot Res. 2006 Mar-Jun; 23 (1–2): 37–43.
10.
EgekvistHBjerringPArendt-NielsenL. Pain and mechanical injury of human skin following needle insertions. Eur J Pain. 1999 Mar; 3 (1): 41–49.
11.
EgekvistHBjerringPArendt-NielsenL. Regional variations in pain to controlled mechanical skin traumas from automatic needle insertions and relations to ultrasonography. Skin Res Technol. 1999; 247–54.
12.
SchneiderLWPeckLSMelvinJW. Penetration characteristics of hypodermic needles in skin and muscle tissue. Phase I (Appendices B-E). Final report. Highway Safety Research Institute, Ann Arbor, MI; 1978. Persistent URL http://hdl.handle.net/2027.42/614.
13.
MiyakoshiMKamoiKIwanagaMHoshiyamaAYamadaA. Comparison of patient's preference, pain perception, and usability between Micro Fine Plus® 31-gauge needle and microtapered NanoPass® 33-gauge needle for insulin therapy. J Diabetes Sci Technol. 2007; 1 (5): 718–724.
14.
AlarconJBHartleyAWHarveyNGMiksztaJA. Preclinical evaluation of microneedle technology for intradermal delivery of influenza vaccines. Clin Vaccine Immunol. 2007 Apr; 14 (4): 375–81.
15.
MiksztaJASullivanVJDeanCWaterstonAMAlarconJBDekkerJP3rdBrittinghamJMHuangJHwangCRFerriterMJiangGMarKSaikhKUStilesBGRoyCJUlrichRGHarveyNG. Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms. J Infect Dis. 2005 Jan 15; 191 (2): 278–88.
16.
BravermanIM. The cutaneous microcirculation. J Invest Dermatol Symp Proc. 2000; 5: 3–9.
17.
PrausnitzMRMitragotriSLangerR. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004 Feb; 3 (2): 115–24.
DavisSPMartantoWAllenMGPrausnitzMR. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans Biomed Eng. 2005 May; 52 (5): 909–15.
20.
GardeniersHJGELuttgeRBerenschotEJWDe BoerMJYeshurunSYHefetzMVan't OeverRVan Den BergA. Silicon micromachined hollow microneedles for transdermal liquid transport. J MEMS. 2003; 12: 855–62.
21.
NordquistLRoxhedNGrissPStemmeG. Novel microneedle patches for active insulin delivery are efficient in maintaining glycaemic control: an initial comparison with subcutaneous administration. Pharm Res. 2007 Jul; 24 (7): 1381–8.
22.
GuptaJFelnerEPrausnitzMR. Microneedles for minimally invasive transdermal insulin delivery: An in vivo study in human diabetic subjects. Proceedings of the 6th Annual Diabetes Technology Meeting; 2006.
23.
KaushikSHordAHDensonDDMcAllisterDVSmitraSAllenMGPrausnitzMR. Lack of pain associated with microfabricated microneedles. Anesth Analg. 2001 Feb; 92 (2): 502–4.
24.
BohannonNJ. Insulin delivery using pen devices. Simple-to-use tools may help young and old alike. Postgrad Med. 1999 Oct 15; 106 (5): 57–64.
25.
DavisSPLandisBJAdamsZHAllenMGPrausnitzMR. Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. J Biomech. 2004 Aug; 37 (8): 1155–63.
26.
YangMZahnJD. Microneedle insertion force reduction using vibratory actuation. Biomed Microdevices. 2004 Sep; 6 (3): 177–82.
27.
MitragotriS. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov. 2006 Jul; 5 (7): 543–8.
28.
CrossSERobertsMS. Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development?. Curr Drug Deliv. 2004 Jan; 1 (1): 81–92.
29.
TouitouEBarryBW, editors. Enhancement in drug delivery. Boca Raton (FL): CRC Press; 2006.
30.
JaniRTriplittCReasnerCDefronzoRA. First approved inhaled insulin therapy for diabetes mellitus. Expert Opin Drug Deliv. 2007 Jan; 4 (1): 63–76.
