Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

OBJECTIVETo determine the minimum alveolar concentration (EC(50) and EC(95)) of sevoflurane in body movement response to surgical incision during combined anesthesia with dexmedetomidine, sevoflurane and fentanyl.

METHODSTwenty-six ASA class I or II patients (aged 18-60 years) underwent selective surgery for lumbar disc herniation under general anesthesia with the combination of with dexmedetomidine, sevoflurane and fentanyl. All the patients received infusion with 0.5 mg/kg dexmedetomidine for 10 min before anesthesia induction with intravenous injection of 3 µg/kg fentanyl 8% sevoflurane inhalation. Upon loss of consciousness, sevoflurane concentration was reduced to 5% with intravenous injection of 1-2 mg/kg succinylcholine, and intubation was started after muscles relaxation. Anesthesia was maintained by sevoflurane and dexmedetomidine (0.2 µg·kg(-1)·h(-1)). Before the surgery, a steady state end-tidal sevoflurane concentration was maintained for at least 10 min. The first patient of the series was tested with 1.5% sevoflurane, and the concentration was adjusted according to modified Dixons up-and-down method (with a step size of 0.2%). Probit analysis was used for calculating EC(50), EC(95) and the 95% confidence interval (CI).

RESULTSThe EC(50) of sevoflurane was 0.94% (95%CI of 0.76%-1.07% ) and EC(95) was 1.23% (95%CI 1.09%-2.05% ).

CONCLUSIONThe EC(50) and EC(95) of sevoflurane are 0.94% and 1.23%, respectively, for suppressing body movement in response to surgical incision during combined anesthesia with sevoflurane, dexmedetomidine and fentanyl.

Adolescent ; Adult ; Anesthesia ; methods ; Anesthetics ; administration & dosage ; Dexmedetomidine ; administration & dosage ; Female ; Fentanyl ; administration & dosage ; Humans ; Male ; Methyl Ethers ; pharmacokinetics ; Middle Aged ; Pulmonary Alveoli ; metabolism ; Reference Values ; Young Adult