DelAQUA Pharmaceuticals Achieves Remarkably High Oral Bioavailability for Poorly Soluble Compounds using Solubilizing Poly(2-oxazoline) Triblock Copolymers

It has been reported that up to 90% of drugs in Pharma discovery pipelines are poorly water soluble and most will fail due to the challenges of delivering an effective dose. We have previously reported how DelAQUA Pharmaceutical’s proprietary poly(2-oxazoline) (POx) triblock copolymers have demonstrated broad and optimizable solubility enhancement for over 80% of the poorly water-soluble drugs we have examined, with increases in solubility over 100,000-fold in some cases. In work performed by our collaborators at Boehringer Ingelheim, we previously reported that an oral nanomicelle formulation of a poorly water-soluble drug prepared with our POx triblock copolymer achieved 100% oral bioavailability (BA) in rats, with a 38-fold increase in C_max and a 6-fold increase in AUC over a standard suspension formulation.

This observation has now been extended to oral delivery of other drugs in our pipeline. In work supported by a KickStart Venture Services Commercialization Grant Award (KickStart Venture Services | Innovate Carolina), the formulation of paclitaxel (PTX) with our patented micelle POxOral+ technology increases oral bioavailability of paclitaxel from the less than 1% reported in the literature to an unprecedented 96% bioavailability in mice (Figure 1A). BA results for paclitaxel using POxOral+ are significantly higher than reported for paclitaxel with other technologies (96% vs 41%) and do not require the fasting and pre-dose treatments utilized previously.

Figure 1: Pharmacokinetic Data of POxol and POxOral+ (https://doi.org/10.15139/S3/Z4PTIA) 

Previous experiments in mice have shown that IV POx/paclitaxel (POxol) was better tolerated than the commercially approved nab-paclitaxel and met the FDA definition of bioequivalence in both Rats and Nonhuman Primates (Hwang et al. Biomaterials, 2023). Surprisingly, after oral treatment in TNBC tumor-bearing mice, we found that paclitaxel accumulation (AUC) in tumors was higher with POxOral+ than for IV POxol (Figure 1B). Paclitaxel C_max was comparable between delivery routes.

This important breakthrough opens the door to DelAQUA’s strategy of reformulation of parenteral products, especially those with poorly soluble drugs, for oral delivery while maintaining high bioavailability and desirable PK/PD parameters. DelAQUA’s innovation in the oral drug delivery space can now deliver improved patient access to critical medicines through highly stable, convenient, and orally bioavailable formulations.

Please watch this space for more exciting news about the broad power of DelAQUA’s technology to impact human and veterinary health, as well as new applications to Crop Protection. There is much more to come.

Inquiries regarding co-development and licensing of products or technologies can be directed to Bruce Frank at bruce@delaquapharma.com, through LinkedIn (https://lnkd.in/eMx7XMfn), or by visiting our website (www.delaquapharma.com).