Abstract
Here we report 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. This robust formulation offers the ability to integrate multiple drugs in a single injection, which is particularly important to address the potential for drug resistance with monotherapy. 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. All drugs released with concentrations above their protein-adjusted inhibitory concentration and retained their physical and chemical properties within the formulation and upon release. 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.
Highlights
We report 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
An ultra-longacting ISFI was developed with the ability to formulate a number of different antiretroviral drugs at high concentrations that can translate to possible applications in humans
Drug stability assessed by differential scanning calorimetry (DSC) analysis shows that drug endotherms are maintained when formulated in the ISFI
Summary
We report 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. Poly(DL-lactide-co-glycolide) (PLGA) is highly soluble in NMP and is biocompatible and biodegradable-eventually degrading to produce glycolic acid and lactic acid monomersmaking it a popular choice as a rate-controlling additive[23] This is not the case for non-biodegradable solid implants, which do require surgical removal once the drug is depleted. Highly solubilizing and water-miscible solvents like NMP lead to rapid phase inversion and the formation of highly porous polymeric networks When designing these ISFI systems for sustained drug delivery, it is important to consider all the aforementioned contributing factors in order to obtain the desired target release kinetics to achieve therapeutic effects. We investigate fourteen (14) antiretroviral drugs for their suitability to be formulated into ISFIs and demonstrate the ability to formulate six (6) of them into ISFIs individually (single drug ISFI) or in combination with one or two other drugs (combination drug ISFI) and achieve sustained plasma concentrations from one month to up to 1 year
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