Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement – A Potential Therapeutic Option for Inflammatory Disorders

• Published in: Pharmaceutical research 2024-06, Vol.41 (6), p.1183-1199
• Main Authors: Arshad, Muhammad Sohail, Hussain, Saad, Zafar, Saman, Rana, Sadia Jafar, Chohan, Tahir Ali, Hamza, Muhammad, Nazari, Kazem, Ahmad, Zeeshan
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Calorimetry; Central nervous system depressants; D-Sorbitol; Dexamethasone; Differential scanning calorimetry; Drug development; Edema; Epidermis; Health aspects; Hydrogen; Hydrogen bonding; Inflammatory diseases; Iontophoresis; Medical Law; Medical research; Medicine, Experimental; Original Research Article; Pharmacology/Toxicology; Pharmacy; Phosphates; Polyvinyl alcohol; Polyvinylpyrrolidone; Skin; Sodium phosphate; Sorbitol; Tetanus antitoxin; Tofacitinib
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-024-03719-w

Aim This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. Methods Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico , in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. Results MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). Conclusion MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases. Graphical Abstract