Abstract
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.
Highlights
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines
In new cases of paediatric HIV infection (o3 years), a ritonavir (RTV)-boosted lopinavir (LPV) oral liquid formulation is World Health Organization (WHO)-recommended as a 4:1 LPV:RTV combination
We describe the extension of this strategy to the accelerated discovery and translation of LPV and LPV/RTV combination solid drug nanoparticles (SDNs) with high drug loading relative to excipients (Z50 wt%) through a unique iterative cycle of materials chemistry and pharmacology, utilizing a novel high-throughput emulsiontemplated freeze-drying (ETFD) screening process, with scale of production subsequently achieved by clinically compliant spray-drying
Summary
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. Nanotherapies often utilize injectable nanocarriers that deliver drug cargoes directly to the bloodstream; daily injections are not practical in many clinical scenarios, such as chronic conditions requiring self-administration over a protracted period Such conditions render many nanomedicine approaches inappropriate, especially if disease is not restricted to targetable organs, creating a prerequisite for oral administration and requiring consideration of inter-related factors such as pharmacokinetics, patient adherence and pill burden. By generating a formulation library with variability in size, surface charge and surface chemistry during screening stages, the identification of optimal nanoparticle properties as they relate to the pharmacology is possible This process is highly translatable and offers the rapid production, evaluation and optimization of cost-effective orally dosed drug nanoparticles to address unmet clinical needs across various diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
