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Enhanced specificity in drug delivery aims to improve upon systemic elution methods by locally concentrating therapeutic agents and reducing negative side effects. Due to their robust physical properties, biocompatibility and drug loading capabilities, nanodiamonds serve as drug delivery platforms that can be applied towards the elution of a broad range of therapeutically-active compounds. In this work, bovine insulin was non-covalently bound to detonated nanodiamonds via physical adsorption in an aqueous solution and demonstrated pH-dependent desorption in alkaline environments of sodium hydroxide. Insulin adsorption to NDs was confirmed by FT-IR spectroscopy and zeta potential measurements, while both adsorption and desorption were visualized with TEM imaging, quantified using protein detection assays and protein function demonstrated by MTT and RT-PCR. NDs combined with insulin at a 4:1 ratio showed 79.8+/-4.3% adsorption and 31.3+/-1.6% desorption in pH-neutral and alkaline solutions, respectively. Additionally, a 5-day desorption assay in NaOH (pH 10.5) and neutral solution resulted in 45.8+/-3.8% and 2.2+/-1.2% desorption, respectively. MTT viability assays and quantitative RT-PCR (expression of Ins1 and Csf3/G-csf genes) reveal bound insulin remains inactive until alkaline-mediated desorption. For applications in sustained drug delivery and therapy we have developed a therapeutic protein-ND complex with demonstrated tunable release and preserved activity.

Gene therapy holds great promise for treating diseases ranging from inherited disorders to acquired conditions and cancers. Nonetheless, because a method of gene delivery that is both effective and safe has remained elusive, these successes were limited. Functional nanodiamonds (NDs) are rapidly emerging as promising carriers for next-generation therapeutics with demonstrated potential. Here we introduce NDs as vectors for in vitro gene delivery via surface-immobilization with 800 Da polyethyleneimine (PEI800) and covalent conjugation with amine groups. We designed PEI800-modified NDs exhibiting the high transfection efficiency of high molecular weight PEI (PEI25K), but without the high cytotoxicity inherent to PEI25K. Additionally, we demonstrated that the enhanced delivery properties were exclusively mediated by the hybrid ND-PEI800 material and not exhibited by any of the materials alone. This platform approach represents an efficient avenue toward gene delivery via DNA-functionalized NDs, and serves as a rapid, scalable, and broadly applicable gene therapy strategy.

Owing to their exceptional biocompatibility and unique surface properties, nanodiamonds (NDs) are shown to be a progressively promising nanomaterial for drug delivery. In this article, NDs as a platform for a host of biomedical applications are described, with an emphasis on cancer therapy, ranging from systemic modalities to primary constituents within polymer hybrid microfilms. Experimental results and theoretical explanations of ND-drug dynamics are compared. Water-dispersion of previously insoluble therapeutics when complexed with NDs demonstrates great promise in expanding current drug delivery options. Various forms of incorporating NDs within microfilms as a localized drug release coating and implant are also discussed.

Nanodiamonds are rapidly emerging as promising carriers for next-generation therapeutics and drug delivery. However, developing future nanoscale devices and arrays that harness these nanoparticles will require unrealized spatial control. Furthermore, single-cell in vitro transfection methods lack an instrument that simultaneously offers the advantages of having nanoscale dimensions and control and continuous delivery via microfluidic components. To address this, two modes of controlled delivery of functionalized diamond nanoparticles are demonstrated using a broadly applicable nanofountain probe, a tool for direct-write nanopatterning with sub-100-nm resolution and direct in vitro single-cell injection. This study demonstrates the versatility of the nanofountain probe as a tool for high-fidelity delivery of functionalized nanodiamonds and other agents in nanomanufacturing and single-cell biological studies. These initial demonstrations of controlled delivery open the door to future studies examining the nanofountain probe's potential in delivering specific doses of DNA, viruses, and other therapeutically relevant biomolecules.

Nanodiamonds (NDs) of 2-8 nm diameters physically bound with the chemotherapeutic agent doxorubicin hydrochloride (DOX) were embedded within a parylene C polymer microfilm through a facile and scalable process. The microfilm architecture consists of DOX-ND conjugates sandwiched between a base and thin variable layer of parylene C which allows for modulation of release. Successive layers of parylene and the DOX-ND conjugates were characterized through atomic force microscopy (AFM) images and drug release assays. Elution rates were tested separately over a period of 8 days and up to one month in order to illustrate the release characteristics of the microfilms. The microfilms displayed the stable and continuous slow-release of drug for at least one month due to the powerful sequestration abilities of the DOX-ND complex and the release-modulating nature of the thin parylene layer. Since the fabrication process is devoid of any destructive steps, the DOX-ND conjugates are unaffected and unaltered. A DNA fragmentation assay was performed to illustrate this retained activity of DOX under biological conditions. Specifically, in this work we have conferred the ability to tangibly manipulate the NDs in a polymer-packaged microfilm format for directed placement over diseased areas. By harnessing the innate ND benefits in a biostable patch platform, extended targeted and controlled release, possibly relevant toward conditions such as cancer, viral infection, and inflammation, where complementary alternatives to systemic drug release enabled by the microfilm devices, can allow for enhanced treatment efficacy.