PURPOSE: To assess the feasibility of transdermal delivery of exenatide (EXT) using low-molecular-weight sodium hyaluronate (HA) dissolving microneedles (MNs) patches for type 2 diabetes mellitus therapy. METHODS: Micromold casting method was used to fabricate EXT-loaded dissolving MNs. The characteristics of prepared MNs including mechanical strength, in vitro/in vivo insertion capacity, dissolution profile and storage stability were then investigated. Finally, the in vivo pharmacokinetics and hypoglycemic effects were compared with traditional subcutaneous (SC) injection. RESULTS: EXT-loaded dissolving MNs made of HA possessed sufficient mechanical strength and the strength could be weakened as the water content increases. The EXT preserved its pharmacological activity during fabrication and one-month storage. With the aid of spring-operated applicator, dissolving MNs could be readily penetrated into the skin in vitro/in vivo, and then rapidly dissolved to release encapsulated drug within 2 min. Additionally, transepidermal water loss (TEWL) determinations showed that skin's barrier properties disrupted by MNs recovered within 10-12 h. Transdermal pharmacokinetics and antidiabetic effects studies demonstrated that fabricated EXT MNs induced comparable efficacy to SC injection. CONCLUSIONS: Our rapidly dissolving MNs patch appears to an excellent, painless alternative to conventional SC injection of EXT, and this minimally invasive device might also be suitable for other biotherapeutics.
PURPOSE: To assess the feasibility of transdermal delivery of exenatide (EXT) using low-molecular-weight sodium hyaluronate (HA) dissolving microneedles (MNs) patches for type 2 diabetes mellitus therapy. METHODS: Micromold casting method was used to fabricate EXT-loaded dissolving MNs. The characteristics of prepared MNs including mechanical strength, in vitro/in vivo insertion capacity, dissolution profile and storage stability were then investigated. Finally, the in vivo pharmacokinetics and hypoglycemic effects were compared with traditional subcutaneous (SC) injection. RESULTS:EXT-loaded dissolving MNs made of HA possessed sufficient mechanical strength and the strength could be weakened as the water content increases. The EXT preserved its pharmacological activity during fabrication and one-month storage. With the aid of spring-operated applicator, dissolving MNs could be readily penetrated into the skin in vitro/in vivo, and then rapidly dissolved to release encapsulated drug within 2 min. Additionally, transepidermal water loss (TEWL) determinations showed that skin's barrier properties disrupted by MNs recovered within 10-12 h. Transdermal pharmacokinetics and antidiabetic effects studies demonstrated that fabricated EXTMNs induced comparable efficacy to SC injection. CONCLUSIONS: Our rapidly dissolving MNs patch appears to an excellent, painless alternative to conventional SC injection of EXT, and this minimally invasive device might also be suitable for other biotherapeutics.
Authors: Sean P Sullivan; Dimitrios G Koutsonanos; Maria Del Pilar Martin; Jeong Woo Lee; Vladimir Zarnitsyn; Seong-O Choi; Niren Murthy; Richard W Compans; Ioanna Skountzou; Mark R Prausnitz Journal: Nat Med Date: 2010-07-18 Impact factor: 53.440
Authors: Kai Jun Koh; Yi Liu; Seng Han Lim; Xian Jun Loh; Lifeng Kang; Chee Yen Lim; Kyle K L Phua Journal: Sci Rep Date: 2018-08-07 Impact factor: 4.379