Charles Virden, founder and CEO of VitalTE, and Lisa Stehno-Bittel, president and founder of Likarda, discuss a new approach to HRT delivery that would allow self-administration through infrequent injection.
Likarda
Sex hormone deficiency affects nearly one-third of all men over 70 years of age as well as nearly all post-menopausal women, who experience dramatic drops in oestrogen levels. Hormone replacement therapies (HRTs) for women during or after menopause and for men with hypogonadism have been a mainstay of treatment for conditions related to ageing for nearly 100 years, with various forms of administration.
Despite the prevalence of need, such therapies are underutilised, with HRT used to treat only about 10% of the men and 5% of women with hormone deficiencies. One of the major challenges of hormone therapy is the short half-life of the hormones once placed in the body.
Improving on pellets
The recent development of new delivery technology has been designed to improve adherence and reach a large, underserved population through a better patient experience. The starting point was the hormone pellet, given its several advantages over most delivery methods as it provides steady serum hormone levels over long periods of time, thus reducing the patient burden.
Despite their impressive safety and efficacy record, pellets have captured a small portion of the HRT market. Due to the size of these pellets, they must be implanted under the skin using specialised equipment in an in-office or outpatient medical procedure, and the process is often not covered by insurance. The widespread use of regular patient self-injections for GLP-1 therapies, insulin, and many other common medications suggests that an injectable HRT – especially one that was required only once every several weeks or months – would be more readily accepted by patients.
Hydrogels to the rescue
Work with hydrogel-based microparticle technology has matured to a stage at which it is now possible to use them as a drug delivery system for multiple modalities. Hydrogels create a meshwork of polymers that trap the hormone or other active ingredient. The size of the holes in the mesh (pores), the durability of the hydrogel in vivo, and the size of the microparticles can all be controlled based on the chemistry used to manufacture the delivery system.
Hydrogel polymer microbeads have the potential to eventually deliver an array of hormones, including peptides. They can dissolve at controlled rates, giving them the potential to deliver molecules or cells to the body while protecting them from immune attack. Gelatin, a collagen-based hydrogel, has been used in research to deliver growth factors to localised areas for a variety of disorders including bone loss, periodontal disease, and hearing loss.
Recently, a collaboration between Likarda and VitalTE resulted in the development and testing of proprietary micropellets of testosterone and oestrogen, encapsulated in a hydrogel shell that is tuned to slow the release of hormone over the course of weeks, for delivery via injection. The entire microbeads are infused with the hormone and released as the hydrogel polymer dissolves. Preclinical studies indicate that the hydrogel microbeads have a release rate similar to pellet delivery, but are injectable, thus eliminating the need for in-office insertion procedures.
Using hydrogel encapsulation, biologics such as hormones can be formulated in aqueous conditions, avoiding organic solvents that can damage peptides. Studies have shown that changing the hydrogel gelation time, swelling ratio, and stiffness can all affect protein and drug release.
There are multiple potential applications of hydrogels for drug delivery, and the research described here offers a straightforward example of a novel microbead approach. The bead format was chosen purposefully to increase the surface area of the therapy, thus improving the absorption of the hormone and uptake into the bloodstream. By introducing a self-administered HRT, delivering microbeads through a small needle, our hope is to increase patient compliance and reach a population in need of a new way forward.