Background

Immobilization of lipase on appropriate solid supports is one way to improve their stability and activity, and can be reused for large scale applications. A sample, cost- effective and high loading capacity method is still challenging.

Results

A facile method of lipase immobilization was developed in this study, by the use of polydopamine coated magnetic nanoparticles (PD-MNPs). Under optimal conditions, 73.9% of the available lipase was immobilized on PD-MNPs, yielding a lipase loading capacity as high as 429 mg/g. Enzyme assays revealed that lipase immobilized on PD-MNPs displayed enhanced pH and thermal stability compared to free lipase. Furthermore, lipase immobilized on PD-MNPs was easily isolated from the reaction medium by magnetic separation and retained more than 70% of initial activity after 21 repeated cycles of enzyme reaction followed by magnetic separation.

Conclusions

Immobilization of enzyme onto magnetic iron oxide nanoparticles via poly-dopamine film is economical, facile and efficient.

Acute lymphoblastic leukemia (ALL) is a blood cancer that is characterized by the overproduction of lymphoblasts in the bone marrow. Treatment for pediatric ALL typically uses combination chemotherapy in phases, including a prolonged maintenance phase with oral methotrexate and 6-mercaptopurine, which often requires dose adjustment to balance side effects and efficacy. However, a major challenge confronting combination therapy for virtually every disease indication is the inability to pinpoint drug doses that are optimized for each patient, and the ability to adaptively and continuously optimize these doses to address comorbidities and other patient-specific physiological changes. To address this challenge, we developed a powerful digital health technology platform based on phenotypic personalized medicine (PPM). PPM identifies patient-specific maps that parabolically correlate drug inputs with phenotypic outputs. In a disease mechanism-independent fashion, we individualized drug ratios/dosages for two pediatric patients with standard-risk ALL in this study via PPM-mediated retrospective optimization. PPM optimization demonstrated that dynamically adjusted dosing of combination chemotherapy could enhance treatment outcomes while also substantially reducing the amount of chemotherapy administered. This may lead to more effective maintenance therapy, with the potential for shortening duration and reducing the risk of serious side effects.

Combination chemotherapy can mediate drug synergy to improve treatment efficacy against a broad spectrum of cancers. However, conventional multidrug regimens are often additively determined, which have long been believed to enable good cancer-killing efficiency but are insufficient to address the nonlinearity in dosing. Despite improved clinical outcomes by combination treatment, multi-objective combination optimization, which takes into account tumor heterogeneity and balance of efficacy and toxicity, remains challenging given the sheer magnitude of the combinatorial dosing space. To enhance the properties of the therapeutic agents, the field of nanomedicine has realized novel drug delivery platforms that can enhance therapeutic efficacy and safety. However, optimal combination design that incorporates nanomedicine agents still faces the same hurdles as unmodified drug administration. The work reported here applied a powerful phenotypically driven platform, termed feedback system control (FSC), that systematically and rapidly converges upon a combination consisting of three nanodiamond-modified drugs and one unmodified drug that is simultaneously optimized for efficacy against multiple breast cancer cell lines and safety against multiple control cell lines. Specifically, the therapeutic window achieved from an optimally efficacious and safe nanomedicine combination was markedly higher compared to that of an optimized unmodified drug combination and nanodiamond monotherapy or unmodified drug administration. The phenotypically driven foundation of FSC implementation does not require any cellular signaling pathway data and innately accounts for population heterogeneity and nonlinear biological processes. Therefore, FSC is a broadly applicable platform for both nanotechnology-modified and unmodified therapeutic optimizations that represent a promising path toward phenotypic personalized medicine.

Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications.

Root canal therapy (RCT) represents a standard of treatment that addresses infected pulp tissue in teeth and protects against future infection. RCT involves removing dental pulp comprising blood vessels and nerve tissue, decontaminating residually infected tissue through biomechanical instrumentation, and root canal obturation using a filler material to replace the space that was previously composed of dental pulp. Gutta percha (GP) is typically used as the filler material, as it is malleable, inert, and biocompatible. While filling the root canal space with GP is the standard of care for endodontic therapies, it has exhibited limitations including leakage, root canal reinfection, and poor mechanical properties. To address these challenges, clinicians have explored the use of alternative root filling materials other than GP. Among the classes of materials that are being explored as novel endodontic therapy platforms, nanodiamonds (NDs) may offer unique advantages due to their favorable properties, particularly for dental applications. These include versatile faceted surface chemistry, biocompatibility, and their role in improving mechanical properties, among others. This study developed a ND-embedded GP (NDGP) that was functionalized with amoxicillin, a broad-spectrum antibiotic commonly used for endodontic infection. Comprehensive materials characterization confirmed improved mechanical properties of NDGP over unmodified GP. In addition, digital radiography and microcomputed tomography imaging demonstrated that obturation of root canals with NDGP could be achieved using clinically relevant techniques. Furthermore, bacterial growth inhibition assays confirmed drug functionality of NDGP functionalized with amoxicillin. This study demonstrates a promising path toward NDGP implementation in future endodontic therapy for improved treatment outcomes.

Posttransplant immunosuppressive drugs such as tacrolimus have narrow therapeutic ranges. Inter- and intraindividual variability in dosing requirements conventionally use physician-guided titrated drug administration, which results in frequent deviations from the target trough ranges, particularly during the critical postoperative phase. There is a clear need for personalized management of posttransplant regimens to prevent adverse events and allow the patient to be discharged sooner. We have developed the parabolic personalized dosing (PPD) platform, which is a surface represented by a second-order algebraic equation with experimentally determined coefficients of the equation being unique to each patient. PPD uses clinical data, including blood concentrations of tacrolimus--the primary phenotypic readout for immunosuppression efficacy--to calibrate these coefficients and pinpoint the optimal doses that result in the desired patient-specific response. In this pilot randomized controlled trial, we compared four transplant patients prospectively treated with tacrolimus using PPD with four control patients treated according to the standard of care (physician guidance). Using phenotype to personalize tacrolimus dosing, PPD effectively managed patients by keeping tacrolimus blood trough levels within the target ranges. In a retrospective analysis of the control patients, PPD-optimized prednisone and tacrolimus dosing improved tacrolimus trough-level management and minimized the need to recalibrate dosing after regimen changes. PPD is independent of disease mechanism and is agnostic of indication and could therefore apply beyond transplant medicine to dosing for cancer, infectious diseases, and cardiovascular medicine, where patient response is variable and requires careful adjustments through optimized inputs.