Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid.
Biological Availability
Animals
Osteoporosis
/ drug therapy
Imidazoles
/ administration & dosage
Diphosphonates
/ administration & dosage
Needles
Rats
Bone Density Conservation Agents
/ administration & dosage
Skin Absorption
/ drug effects
Drug Delivery Systems
/ methods
Administration, Cutaneous
Rats, Sprague-Dawley
Skin
/ metabolism
Male
Solubility
Drug Liberation
Administration, Oral
bioavailability
dissolving microneedles
drug loading
minodronic acid
osteoporosis
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
23 Oct 2024
23 Oct 2024
Historique:
received:
13
06
2024
accepted:
29
09
2024
medline:
24
10
2024
pubmed:
24
10
2024
entrez:
23
10
2024
Statut:
epublish
Résumé
Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance. To tackle these issues, we developed MA-loaded dissolving microneedles (MA-MNs) with significantly improved bioavailability for osteoporosis therapy. We investigated the influence of drug loading on the physicochemical properties, transdermal permeation behavior, and pharmacokinetics of MA-MNs. The drug loading of MA-MNs exerted almost no effect on their morphology, mechanical property, and skin insertion ability, but it compromised the transdermal permeability and bioavailability of MA-MNs. Compared with oral MA, MA-MNs with the lowest drug loading (224.9 μg/patch) showed a 9-fold and 25.8-fold increase in peak concentration and bioavailability, respectively. This may be ascribed to the reason that the increased drug loading can generate higher burst release, higher drug residual rate, and drug supersaturation effect in skin tissues, eventually limiting drug absorption into the systemic circulation. Moreover, MA-MNs prolonged the half-life of MA and provided more steady plasma drug concentrations than intravenously injected MA, which helps to reduce dosing frequency and side effects. Therefore, dissolving MNs with optimized drug loading provides a promising alternative for bisphosphonate drug delivery.
Identifiants
pubmed: 39443354
doi: 10.1208/s12249-024-02963-y
pii: 10.1208/s12249-024-02963-y
doi:
Substances chimiques
Imidazoles
0
Diphosphonates
0
Bone Density Conservation Agents
0
YM 529
127657-42-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
252Informations de copyright
© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
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