Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

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.

Current research toward optimizing dosing of first-line antituberculosis treatment

“…Emerging techniques allow exploration of the potential for novel costefficient formulations to improve drug delivery. Nanoparticle formulations, for example, may potentially extend the product shelf-life, improve safety and tolerability, enhance the pharmacokinetic profile to optimize the key pharmacokinetic measures related to drug activity, and reduce pharmacokinetic variability [122]. Moreover, more efficient absorption into the systemic circulation may allow reduced content of the active ingredient, thereby making the drug more affordable.…”

High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing

“…In this regards, Giardiello et al developed an accelerated nanomedicine platform to generate a potential aqueous pediatric human immunodeficiency virus (HIV) nanotherapy, targeting oral dose, with clinical translation and regulatory approval for human evaluation. Giardiello et al's small‐scale screening used 1 mg of drug compound, generating large libraries of solid drug nanoparticles (160 individual components), and iterative pharmacological and chemical evaluation established potential candidates for progression through to clinical manufacture.…”

Intracellular delivery of nano‐formulated antituberculosis drugs enhances bactericidal activity

“…There are ongoing clinical trials of lopinavir and Efavirenz SDNs to treat HIV (Eudract number 2013‐004913‐41), thus showing the feasibility and potential of using SDNs to treat human diseases (Giardiello et al . ).…”

“…Although SDNs would be viewed as novel drugs by the Medicines and Healthcare Products Regulatory Agency, as all the products are FDA approved, progression to clinical studies may be fast tracked. There are ongoing clinical trials of lopinavir and Efavirenz SDNs to treat HIV (Eudract number 2013-004913-41), thus showing the feasibility and potential of using SDNs to treat human diseases (Giardiello et al 2016).…”

“…Solid drug nanoparticles of the first line TB antibiotics; RIF, RIF + INH (DUAL) and RIF + INH + PZA (TRIPLE) were synthesised and characterised via either an emulsion template freeze dried or emulsion spray dried method described previously (Giardiello et al 2016;Zhang et al 2008). Drug loading, size, and Zeta potential of the tested SDNs (in Middlebrooks 7H9 broth) are provided in Tables 1a and 1b.…”