Microneedle-Mediated Delivery of Amikacin-Liposomes: A Minimally Invasive Strategy against Bacterial Septicemia

Purpose: Sepsis is a severe systemic infection with a high mortality rate worldwide. Majorly, sepsis is treated by administering antibiotics including amikacin. Nevertheless, the present course of therapy necessitates frequent bolus doses of amikacin, leading to patient non-adherence, prolonged hospital stays, and regular therapeutic monitoring. Administration of amikacin by the intravenous or intramuscular routes requires precise dosage calculations, and appropriate disposal of sharp wastes. Amikacin’s shorter half-life makes it more challenging to administer intravenously and achieve adequate systemic concentrations. An innovative formulation and delivery approach to combat infection, particularly in a low-resource healthcare setting can be lifesaving to many, by reducing errors due to inappropriate needle disposal and expanding access to outpatient antibiotic treatment. Methods: In response to the challenge, novel delivery systems were fabricated, including microneedle (MN) patches containing amikacin (Ak-MN) and amikacin-loaded liposomes (Ak-lip-MN). These systems were designed to offer sustained and extended delivery, to improve the treatment of infections. The Ak-MN and Ak-lip-MN were prepared using the PDMS micro-molding technique and evaluated for their piercing strength, in vivo skin insertion, pharmacokinetics, and stability. Results: The higher TEWL value of 375.6 g/m²/h and the histological studies showed good MN skin insertion. The developed MN patches demonstrated a prolonged release profile lasting as long as 96 h, with maximum plasma concentrations (C_max) of 450 ng/mL for Ak-MN and 250 ng/mL for Ak-lip-MN. This can lower continual dosage administration and enhance the antibacterial efficacy at reduced doses, making way for effective treatment approaches for the management of sepsis. Conclusion: The study overcomes the drawbacks of traditional intravenous injections, by developing dissolving microneedles with improved therapeutic efficacy.