Adherence to a strict HIV regimen is an essential part of effective HIV treatment. Medication should be taken every day, at specific times of the day, and with or without certain kinds of food. Making this process easier would, undoubtedly, increase medication adherence and improve the efficacy of current HIV treatment plans.
Now, a group of researchers from the University of North Carolina (UNC) at Chapel Hill reports an ultra-long-acting tunable, biodegradable, and removable polymer-based delivery system that offers sustained drug delivery for up to one year for HIV treatment or prophylaxis. The work is published in a paper that appears in Nature Communications titled “Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery”.
The authors write that the goal of this seven-year study in animals was to develop a delivery system that can offer ultra-long-acting drug release by (1) providing flexibility in the choice of active ingredient, (2) sustained release for weeks or months, (3) the ability to be surgically removed in case of an allergic or adverse reaction, (4) and the ability to integrate multiple drugs.
The team investigated 14 antiretroviral drugs for their suitability to be formulated into in situ forming implants (ISFIs). Six antiretroviral drugs were selected based on their solubility in N-methyl-2-pyrrolidone and relevance as a combination therapy for HIV treatment or prevention. The six were able to be formulated into ISFIs individually or in combination with one or two other drugs. All six kept their physical and chemical properties within the formulation and upon release, and were released from the implant at effective levels for a sustained amount of time ranging from one month to a year.
“There is no FDA-approved or marketed technology for long-acting prevention of HIV, and we are the first to use this delivery method with multiple antiretroviral drugs,” said Rahima Benhabbour, PhD, first author of the study and assistant professor in the UNC/NC State University (NCSU) joint department of biomedical engineering. “To have an HIV prevention treatment that consists of an injection once or twice a year would make an incredible impact for patients.” She added, “This technology is not only promising for HIV, but for any kind of condition that requires a daily intake of medication. We’re talking about a safe, removable, long-lasting injection that takes away the burden of adhering to a daily medication regimen.”
The injectable implant is comprised of three elements—an organic solvent, a polymer, and the drug or drugs that need to be delivered. The formulation results in a honey-like liquid that turns into a solid when injected under the skin. This phase inversion happens when the solvent diffuses into the body leaving behind the polymer and medication(s)—the combination of which determines over what time period the medication(s) will be released into the blood system.
“In sub-Saharan Africa where prevalence of HIV is highest, accessibility to these medications can be difficult, and there is much stigma associated with the virus,” Benhabbour said. “It is a very big deal for someone who doesn’t have HIV to go out of their way to not only access the drugs, but then associate themselves with HIV by taking a pill every day.” There’s also the factor of human error in adherence to a strict schedule. And, small deviations in a schedule can make antiretroviral drugs less effective.
The injectable drug implant created by UNC’s research team is the first to address several drawbacks to the current method of long-acting drug delivery for HIV—namely the ability to remove it and quickly eliminate the presence of residual drug(s) in the system.
“If a patient needs to withdraw from the treatment because they’ve had a bad reaction to the drug(s), or maybe a woman has become pregnant, our implant can be easily surgically removed,” said Martina Kovarova, PhD, contributing author to the study and associate professor of medicine at UNC School of Medicine.
This is the first ever injectable implant for HIV that can be removed as early as one week, or as late as months after the injection, and have drug levels virtually eliminated from the system within one week. If the implant does not need to be removed, it biodegrades into lactic and glycolic acids, which are already found in the body and are easily absorbed.
The authors write that the “versatility of this formulation to integrate multiple drugs and provide sustained plasma concentrations from several weeks to up to one year, combined with its ability to be removed to terminate the treatment if necessary, makes it attractive as a drug delivery platform technology for a wide range of applications.” Researchers plan to continue developing and improving this multi-drug delivery system, observing its effects in relevant in vivo models and eventually humans.