Pharmacokinetics and dopaminergic effect of dopamine agonist 5-OH-DPAT in vivo were determined following transdermal iontophoresis in rats based on drug concentration in plasma (C(p)) and dopamine levels in striatum (C(DA)). Correlation of the in vitro transport with the pharmacokinetic-pharmacodynamic (PK-PD) profiles was characterized in the transport in dermatomed rat skin (DRS) and rat stratum corneum (RSC). The integrated in vivo PK-PD and in vitro transport models successfully described time course of C(p), C(DA), and in vitro flux in DRS and RSC. Population value of steady-state flux (J(ss)) in vivo (31 nmol/cm(2) . h with 95% confidence interval (CI) = 20-41) is closer to J(ss) in vitro in DRS (61 nmol/cm(2) . h, CI = 54-67) than in vitro J(ss) in RSC (98 nmol/cm(2) . h, CI = 79-117). On the other hand, skin release rate constant (K(R)) in vivo was similar to the K(R) in RSC (4.8/h, CI = 2.4-7.1 vs. 2.6/h, CI = 2.5-2.6). Kinetic lag time (t(L)) in vivo was negligible, which is close to in vitro t(L) in RSC (0.0 h, CI = 0.0-0.1). Based on nonlinear mixed-effect modeling, profiles of C(p) and C(DA) were successfully predicted using in vitro values of J(ss) in DRS with K(R) and t(L) in RSC. A considerable dopaminergic effect was achieved, indicating the feasibility to reach therapeutically effective concentrations of 5-OH-DPAT upon transdermal iontophoresis.
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http://dx.doi.org/10.1002/jps.20528 | DOI Listing |
Int J Pharm
December 2024
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
Transdermal drug delivery presents numerous advantages over conventional administration routes, including non-invasiveness, enhanced patient adherence, circumvention of hepatic first-pass metabolism, self-administration capabilities, controlled release, and increased bioavailability. Nevertheless, the barrier function of stratum corneum limits this strategy to molecules possessing requisite physicochemical attributes. To expand the field of transdermal delivery, researchers have pioneered physical enhancement techniques, with micron-sized needles emerging as a particularly promising platform for the transdermal and intradermal delivery of therapeutic agents across a spectrum of molecular sizes.
View Article and Find Full Text PDFSensors (Basel)
November 2024
Research Unit of Electronics for Sensor Systems, Department of Engineering, University Campus Bio-Medico di Roma, 00128 Rome, Italy.
Electrical stimulation can be used in several applications such as fatigue reduction, muscle rehabilitation, neurorehabilitation, neuro-prosthesis and pain relief. Moreover, electrical stimulation can be used for drug delivery applications or body fluids extraction (e.g.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Research Institute for Biomaterials, Tech Institute for Advanced Materials Bioinspired Biomedical Materials & Devices Center, College of Materials Science and Engineering, Jiangsu Collaborative Innovation Center for Advanced Inorganic Function Composites, Suqian Advanced Materials Industry Technology Innovation Center, Nanjing Tech University, Nanjing 211800, China.
Transdermal insulin delivery in a painless, convenient, and on-demand way remains a long-standing challenge. A variety of smart microneedles (MNs) fabricated by glucose-responsive phenylboronic acid hydrogels have been previously developed to provide painless and autonomous insulin release in response to a glucose level change. However, like the majority of MNs, their transdermal delivery efficiency was still relatively low compared to that with subcutaneous injection.
View Article and Find Full Text PDFJ Therm Biol
December 2024
School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK; Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK. Electronic address:
Drug Deliv Transl Res
November 2024
School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom.
Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays.
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