Remote loading of minoxidil in nano-reservoirs leads to polymorphism and controlled release

Abstract

Alopecia, a condition characterized by hair loss leading to baldness, treated with minoxidil, has the side effects of scalp irritation and lowering of blood pressure. However, administering minoxidil through remote drug loading and controlled release using lipid vesicles can be challenging, particularly for scalp applications in conditions like alopecia. Controlled release nano-medicine (CRNM) that delivers the minoxidil, using engineered nanoparticles, locally at a predetermined rate can overcome these side effects. For that, a novel minoxidil-loaded “shape anisotropic lipid nanoparticle” (SALN) is developed with a given composition and optimized for ultrasound processing conditions. That renders SALN with properties like multi-chambered bulk architecture with nano-reservoirs and shape anisotropy, with ultrasound activation, remote-loading, and controlled-release properties. The nanoparticles exhibited entrapment efficiency (32.2%) and drug release (99.01%) over 48 h and showed zero-order release kinetics. The nanoparticles are anisotropic as per HR-TEM. The HR-TEM studies showed that the SALN has a honeycomb-like bulk architecture with interconnected drug-loaded nano-reservoirs. It also revealed that the drug remains in different polymorphs at nanoscale inside the multi-chambered nano-reservoirs by DSC, TGA, and XRD. Drug release is significantly enhanced due to this nanoscale effect. The results of the design of experiments (DOE) to experimentally validated results are within 10% deviation. Moreover, the proposed controlled release system (SALN) for alopecia could improve local delivery to the hair follicle and is subjected to further studies. Subsequent research and development in this field can potentially revolutionize the management of alopecia and offer more effective and well-tolerated treatment options for patients.