Preclinical Pharmacokinetic and Pharmacodynamic Evaluation of Intradermal Growth hormone and Insulin Delivery using Novel Microneedles in Guinea pigs and Rats

Abstract ID 91229 Poster Board 201 Abstract TextIntroduction: Microneedles facilitate drug delivery into the dermis layer of skin, with minimum pain. However, their safety and efficacy need to be confirmed. Objective: We evaluated the safety and efficacy of novel, indigenously developed microneedles, through the two different animal models i.e. intradermal administration of growth hormone in guinea pigs and intradermal administration of insulin in rats, comparing the pharmacokinetics and pharmacodynamics against conventional intramuscular, subcutaneous and intradermal administration. Method: Study used 750 μm long, 200 μm bore microneedles on two animal models: Thirty Dunkin Hartley guinea pigs (females, 6-8 months, 500-600g) received 1mg/kg rhGH. Administered IM with 23G needle (n = 10), ID with 26G needle (n = 10), or ID with microneedle (MN) (n=10). Blood samples collected over 4 hours from hind leg's saphenous vein for GH assessment via electrochemiluminescence assay. Thirty Sprague Dawley rats (males, 3-4 months, 200-250g) received 3 IU/kg insulin via SC with 23G needle (n=10), ID with 26G needle (n = 10), or ID with MN (n = 10). Insulin and glucose levels measured at 0, 15, 30, 60, 90, 120, 180 minutes using electrochemiluminescence assay and the hexokinase-6-PDH method, respectively. Safety assessment for both models included monitoring for signs of bleeding, erythema, swelling, and pain using the guinea pig pain scoring system and rat grimace scale. Efficacy evaluation encompassed pharmacokinetic parameters (AUC, Cmax, Tmax, and T1/2) for rhGH and insulin, alongside insulin's pharmacodynamics (changes in glucose levels). Mean and standard deviation were used for statistical analysis, with p-values determined via ANOVA to ascertain significance. Results: Microneedle injections showed no bleeding, erythema, swelling, or pain, ensuring safety. For guinea pigs, plasma growth hormone levels were comparable: MN vs ID (p = 0.41), MN vs IM (p = 0.0001), ID vs IM (p = 0.0024). Bioavailability (AUC) averaged 348.72 (±81.23) ng.h/ml for MN, 444.7 (±45.88) ng.h/ml for ID, and 705.71 (±254.78) ng.h/ml for IM injections. Mean Cmax values were 125.16 (±27.45) ng/ml for MN, 160.92 (±38.35) ng/ml for ID, and 297.4 (±142.01) ng/ml for IM. Mean Tmax values were 78 (±42.89) min for MN, 75 (±29.15) min for ID, and 120 (±0) min for IM. The mean T1/2 were 1.98 (±1.58) hr for MN, 2.529 (±1.52) hr for ID, and 0.81 (±0.17) hr for IM. For rats, plasma insulin levels were comparable: MN vs ID (p = 0.93), MN vs SC (p = 0.062), ID vs SC (p = 0.068). Plasma glucose levels showed no significant difference: MN vs ID (p = 0.92), MN vs SC (p = 0.98), ID vs SC (p = 0.85). Bioavailability (AUC) averaged 272.97 (±202) ng.h/ml for MN, 288.48 (±241.72) ng.h/ml for ID, and 349.01 (±215.68) ng.h/ml for SC injections. Mean Cmax values were 212.7 (±111.45) μU/ml for MN, 278.06 (±220.93) μU/ml for ID, and 429.81 (±335.92) μU/ml for SC. Mean Tmax values were 48.33 (±23.45) min for MN, 46.67 (±20.46) min for ID, and 28.33 (±5.00) min for SC. Mean T1/2 were 0.61 (±0.57) hr for MN, 0.47 (±0.38) hr for ID, and 0.78 (±1.17) hr for SC. Conclusion: Microneedle intradermal delivery had comparable safety and efficacy, paving the way for human clinical studies. Conflict of Interest: None No funding or support provided