The performance of a 3D-printed personalized sustained delivery device is demonstrated for the first time in humans.

Low drug loading and instability in blood circulation are two key challenges that impede the successful clinical translation of nanomedicine, as they result in only marginal therapeutic efficacy and toxic side effects associated with premature drug leakage, respectively. Herein, highly stable and ultrahigh drug loading micellar nanocomplexes (MNCs) based on the self-assembly of the anticancer drug doxorubicin (DOX) and a poly(ethylene glycol)-epigallocatechin-3-O-gallate (EGCG) conjugate are developed. The formation of these MNCs is facilitated by strong favorable intermolecular interactions between the structurally similar aromatic EGCG and DOX molecules, which impart exceptionally high drug-loading capability of up to 88% and excellent thermodynamic and kinetic stability. Unlike two clinical formulations of DOX-free DOX and liposomal DOX, which are not effective below their lethal dosages, these DOX-loaded MNCs demonstrate significant tumor growth inhibition in vivo on a human liver cancer xenograft mouse model with minimal unwanted toxicity. Overall, these MNCs can represent a safe and effective strategy to deliver DOX for cancer therapy.

The recent advances in the design of injectable hydrogels for stem cell delivery, especially for in vivo applications, are overviewed in this review.

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Polyethyleneimine (PEI) is widely regarded as one of the most efficient non-viral transfection agents commercially available. However, a key concern is its pronounced cytotoxicity, ascribed mainly to its high amine content and cationic charge density. Significant past efforts to mitigate its toxicity usually involved lengthy synthetic procedures. We now propose a simple strategy using hydrogen peroxide (H2O2) to oxidize the amine groups. PEI/DNA complexes were first formed before some amine groups were removed with H2O2. This reduced surface charge while the remaining cationic charges still allowed for efficient transfection. The DNA was not damaged and remained bound after oxidation. Furthermore, H2O2 was quantitatively removed with sodium pyruvate prior to cell culture. Oxidized complexes caused no cytotoxicity even at high polymer concentrations. Compared to non-oxidized complexes used at subtoxic doses, oxidized complexes mediated significantly more GFP expression. A key strength of this approach is its simplicity as it involves only simple mixing of solutions. This strategy promises to further realize the potential of using PEI for the delivery of nucleic acids or other cargos.