Optimization studies of Lipidic vesicles utilizing CCD for enhanced permeation of phenylephrine for effective management of Chemotherapy Induced Alopecia

Ravi Shankar ^1* Prabhat Kumar Upadhyay ¹ Manish Kumar ²

• ¹ Institute of Pharmaceutical Research, GLA University, Mathura, India
• ² Indo-Soviet Friendship College of Pharmacy, Moga, Punjab, India

Background: Chemotherapy-induced alopecia (CIA) is a prevalent and distressing adverse effect of cancer treatment, often leading to therapy non-compliance. Current preventive strategies, such as scalp cooling, have limitations. This study aimed to develop and optimize phenylephrine-loaded invasomes for enhanced dermal drug delivery and sustained vasoconstriction to mitigate CIA.A rotatable three-level two-factor Central Composite Design (CCD) was employed to optimize invasomal formulations by evaluating vesicle size (PS), polydispersity index (PDI), and entrapment efficiency (EE%). The optimized invasomal dispersion was formulated using lipoid 80 and D-limonene was incorporated into a Carbopol-based hydrogel for sustained drug release. Formulations were characterized for vesicular morphology, zeta potential, drug entrapment, in-vitro drug release, and ex-vivo permeation studies using goat skin. Statistical models were validated using ANOVA.The developed invasomes had a vesicle size range of 172 ± 3.2 nm to 435 ± 3.5 nm, with an entrapment efficiency of 52.5% to 81.67%. The optimized invasomes were having vesicle size of 162 ± 18 nm and zeta potential of -28.9 mV. The invasomal gel exhibited significantly higher cumulative drug permeation (59.34 ± 2.34%) compared to conventional gel (19.97 ± 0.86%) (p < 0.005), confirming enhanced dermal delivery. Drug release followed a Higuchi diffusion model, indicating controlled and sustained release for deeper dermal penetration.The developed phenylephrine-loaded invasomal gel demonstrated superior drug penetration and sustained release, suggesting its potential as a novel, non-invasive strategy for chemotherapy-induced alopecia management. Future studies should focus on in-vivo validation and long-term stability assessments for clinical translation.