A Post-Marketing Drug Evaluation Framework Based on Real-World Electronic Health Records Data.

Real-world data (RWD) could be a new way to evaluate the safety and efficacy of post-marketing drugs, while there is no common method for how to use RWD for drug evaluation. In this paper, we present a framework for real-world drug evaluation based on electronic medical record (EHR) data. We designed a data model customized for post-marketing drug evaluation and a unified post-marketing drug evaluation pipeline. The proposed framework can be applied to drug evaluations with different study paradigms for different purposes by flexible use of the proposed data model and pipeline. A prototype system has been developed according to the framework. Real-world EHRs in a tertiary hospital in China between 2010 and 2020 were converted to the proposed data model, and as a test case, we conducted a research on the risk of allergic reactions to cefodizime and ceftriaxone using the prototype system.

Bioengineered hydrogels enhance ex vivo preservation of patient-derived tumor explants for drug evaluation.

Ex vivo patient-derived tumor slices (PDTS) are currently limited by short-term viability in culture. Here, we show how bioengineered hydrogels enable the identification of key matrix parameters that significantly enhance PDTS viability compared to conventional culture systems. As demonstrated using single-cell RNA sequencing and high-dimensional flow cytometry, hydrogel-embedded PDTS tightly preserved cancer, cancer-associated fibroblast, and various immune cell populations and subpopulations in the corresponding original tumor. Cell-cell communication networks within the tumor microenvironment, including immune checkpoint ligand-receptor interactions, were also maintained. Remarkably, our results from a co-clinical trial suggest hydrogel-embedded PDTS may predict sensitivity to immune checkpoint inhibitors (ICIs) in head and neck cancer patients. Further, we show how these longer term-cultured tumor explants uniquely enable the sampling and detection of temporal evolution in molecular readouts when treated with ICIs. By preserving the compositional heterogeneity and complexity of patient tumors, hydrogel-embedded PDTS provide a valuable tool to facilitate experiments targeting the tumor microenvironment.

Taletrectinib for the treatment of ROS-1 positive non-small cell lung cancer: a drug evaluation of phase I and II data.

INTRODUCTION: While crizotinib and entrectinib have been approved to treat ROS1 fusion-positive (ROS1+) non-small-cell lung cancer (NSCLC), unmet needs remain. These unmet needs include treatment options for patients with resistance mutations and efficacious options even in the presence of brain metastasis while simultaneously avoiding unwanted neurological side effects. AREAS COVERED: Taletrectinib was designed to: improve efficacy; overcome resistance to first-generation ROS1 inhibitors; and address central nervous system penetration while conferring fewer neurological adverse events. All of these features are demonstrated and supported by data from the phase I and the regional phase II TRUST-I clinical trial. Here, we describe the preclinical and clinical characteristics of taletrectinib and evaluate the data from phase I and II studies and review the rationale and design of TRUST-II, a global phase II study of taletrectinib, which is enrolling patients in North America, Europe, and Asia. EXPERT OPINION: Taltrectinib has the potential to improve PFS based on its greater potency against ROS1+ tumors and high CNS penetration. By selectively inhibiting ROS1 wild-type and its resistant mutations over TRKB, taltrectinib has a better safety profile with minimal CNS-related AEs compared to other ROS1+ inhibitors.

Using Bayesian Dynamic Borrowing to Maximize the Use of Existing Data: A Case-Study.

Bayesian Dynamic Borrowing (BDB) designs are being increasingly used in clinical drug development. These methods offer a mathematically rigorous and robust approach to increase efficiency and strengthen evidence by integrating existing trial data into a new clinical trial. The regulatory acceptability of BDB is evolving and varies between and within regulatory agencies. This paper describes how BDB can be used to design a new randomised clinical trial including external data to supplement the planned sample size and discusses key considerations related to data re-use and BDB in drug development programs. A case-study illustrating the planning and evaluation of a BDB approach to support registration of a new medicine with the Center for Drug Evaluation in China will be presented. Key steps and considerations for the use of BDB will be discussed and evaluated, including how to decide whether it is appropriate to borrow external data, which external data can be re-used, the weight to put on the external data and how to decide if the new study has successfully demonstrated treatment benefit.

Human Motor System-Based Biohybrid Robot-On-a-Chip for Drug Evaluation of Neurodegenerative Disease.

Biohybrid robots have been developed for biomedical applications and industrial robotics. However, the biohybrid robots have limitations to be applied in neurodegenerative disease research due to the absence of a central nervous system. In addition, the organoids-on-a-chip has not yet been able to replicate the physiological function of muscle movement in the human motor system, which is essential for evaluating the accuracy of the drugs used for treating neurodegenerative diseases. Here, a human motor system-based biohybrid robot-on-a-chip composed of a brain organoid, multi-motor neuron spheroids, and muscle bundle on solid substrateis proposed to evaluate the drug effect on neurodegenerative diseases for the first time. The electrophysiological signals from the cerebral organoid induced the muscle bundle movement through motor neuron spheroids. To evaluate the drug effect on Parkinson's disease (PD), a patient-derived midbrain organoid is generated and incorporated into a biohybrid robot-on-a-chip. The drug effect on PD is successfully evaluated by measuring muscle bundle movement. The muscle bundle movement of PD patient-derived midbrain organoid-based biohybrid robot-on-a-chip is increased from 4.5 ± 0.99 µm to 18.67 ± 2.25 µm in response to levodopa. The proposed human motor system-based biohybrid robot-on-a-chip can serve as a standard biohybrid robot model for drug evaluation.

Relação entre benefício e risco em interações medicamentosas nas prescrições médicas de um hospital universitário no estado de São Paulo / Benefit-risk relationship in drug interactions in prescriptions from a university hospital in the state of São Paulo / Relación beneficio-riesgo en interacciones medicamentosas en prescripciones de un hospital universitario del estado de São Paulo

Objetivo: Avaliar interações medicamentosas (IM), em que os riscos se so- brepõem aos benefícios (nível I) ou os benefícios se sobrepõem aos riscos (nível II); a partir da análise retrospectiva de prescrições médicas em um Hospital Universitário no estado de São Paulo, Brasil. Métodos: Foram analisadas 19762 prescrições médicas des- tinadas à farmácia do hospital, de janeiro a setembro de 2009; com o auxílio de programas sobre IM, para categorizar IM de nível I e II. Resultados: Na análise 26,53% apresentaram IM, em que 23,64% foram classificadas em nível I e 76,35% em nível II. Dentre as IM com maior frequência no nível I, estavam: ácido acetilsalicílico (AAS) e clopidogrel, AAS e heparina, captopril e espironolactona, digoxina e hidroclorotiazida. Houve uma redução em percentual de IM de nível I, comparando janeiro representado por 26,5% e setembro representado por 18,4%. Já nas IM de nível II, tem-se as seguintes associações com maior frequência: AAS e propranolol, AAS e insulina regular humana, AAS e ate- nolol, AAS e enalapril, AAS e carvedilol. Conclusão: A atuação dos farmacêuticos cola- borou à redução de IM de nível I, devido à intervenção por meio de comunicação estabe- lecida com os prescritores; sinalizando a importância da equipe interprofissional em saúde.

Objective: To evaluate drug interactions (MI), in which risks outweigh the benefits (level I) or benefits outweigh the risks (level II); from the retrospective analysis of medical prescriptions in a University Hospital in the state of São Paulo, Brazil. Methods: 19,762 prescriptions destined to the hospital pharmacy were analyzed, from January to September 2009; with the help of programs on MI, to categorize level I and II MI. Results: In the analysis 26.53% presented MI, in which 23.64% were classified in level I and 76.35% in level II. Among the most frequent level I MI were: acetylsalicylic acid (ASA) and clopidogrel, ASA and heparin, captopril and spironolactone, digoxin and hydrochlorothiazide. There was a reduction in the percentage of level I MI, comparing January, which accounted for 26.5%, and September, which accounted for 18.4%. As for level II MI, the following associations were more frequent: ASA and propranolol, ASA and regular human insulin, ASA and atenolol, ASA and enalapril, ASA and carvedilol. Conclusion: The role of pharmacists collaborated to the reduction of level I MI, due to the intervention by means of communication established with the prescribers; signaling the importance of the interprofessional health team.

Objetivo: Evaluar las interacciones medicamentosas (IM), en las que los riesgos superan a los beneficios (nivel I) o los beneficios superan a los riesgos (nivel II); a partir del análisis retrospectivo de las prescripciones médicas en un Hospital Universitario del estado de São Paulo, Brasil. Métodos: Se analizaron 19.762 prescripciones destinadas a la farmacia del hospital, de enero a septiembre de 2009; con la ayuda de programas sobre IM, para categorizar los IM de nivel I y II. Resultados: En el análisis el 26,53% presentaron IM, en el que el 23,64% se clasificaron en nivel I y el 76,35% en nivel II. Entre los IM de nivel I más frecuentes estaban: ácido acetilsalicílico (AAS) y clopidogrel, AAS y heparina, captopril y espironolactona, digoxina e hidroclorotiazida. Hubo una reducción del porcentaje de IM de nivel I, comparando enero, que supuso el 26,5%, y septiembre, que supuso el 18,4%. En cuanto a los IM de nivel II, fueron más frecuentes las siguientes asociaciones: AAS y propranolol, AAS e insulina humana regular, AAS y atenolol, AAS y enalapril, AAS y carvedilol. Conclusiones: El papel de los farmacéuticos colaboró a la reducción de las IM de nivel I, debido a la intervención mediante la comunicación establecida con los prescriptores; señalando la importancia del equipo sanitario interprofesional.

Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography.

This study aims at demonstrating label-free drug-response-patterns assessment of different tumor spheroids and drug types by dynamic optical coherence tomography (D-OCT). The study involved human breast cancer (MCF-7) and colon cancer (HT-29) spheroids. The MCF-7 and HT-29 spheroids were treated with paclitaxel (Taxol; PTX) and the active metabolite of irinotecan SN-38, respectively. The drugs were applied with 0 (control), 0.1, 1, and 10 µM concentrations and the treatment durations were 1, 3, and 6 days. A swept-source OCT microscope equipped with a repeated raster scanning protocol was used to scan the spheroids. Logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDS[Formula: see text]) algorithms were used to visualize the tumor spheroid dynamics. LIV and OCDS[Formula: see text] images visualized different response patterns of the two types of spheroids. In addition, spheroid morphology, LIV, and OCDS[Formula: see text] quantification showed different time-courses among the spheroid and drug types. These results may indicate different action mechanisms of the drugs. The results showed the feasibility of D-OCT for the evaluation of drug response patterns of different cell spheroids and drug types and suggest that D-OCT can perform anti-cancer drug testing.

Leucine Aminopeptidase-Mediated Multifunctional Molecular Imaging Tool for Diagnosis, Drug Evaluation, and Surgical Guidance of Liver-Related Diseases.

Traditional molecular imaging tools used for detecting liver diseases own several drawbacks, such as poor optical performance and limited applicability. Monitoring the concentration of leucine aminopeptidase (LAP), which is closely related to liver diseases such as liver cancer and liver injury, and analyzing it in diagnosis, drug evaluation, and surgical treatment is still a challenging task. Herein, we construct an intramolecular charge-transfer mechanism-based, ultrasensitive, near-infrared fluorescent probe (LAN-lap) for dynamic monitoring of LAP fluctuations in living systems. LAN-lap, with high specificity, stability, sensitivity, and water solubility, can achieve in vitro monitoring of LAP through both fluorescence and colorimetric methods. Moreover, LAN-lap can successfully be used for the localization imaging of endogenous LAP, confirming the upregulation of LAP expression in liver cancer and liver injury cells. In addition, LAN-lap can realize the imaging of liver tumors in living organisms. Meanwhile, it can intuitively present the degree of drug-induced liver injury, achieving semi-quantitative imaging evaluation of the hepatotoxicity of two drugs. Furthermore, LAN-lap can track liver cancer tumors in mice with peritoneal metastasis and can assist in fluorescence-guided surgical resection of liver cancer tumors. This multifunctional LAN-lap probe could play an important role in facilitating simultaneous diagnoses, imaging, and synergistic surgical navigation to achieve better point-of-care therapeutic efficacy.

Use of Real-World Evidence for Drug Regulatory Decisions in China: Current Status and Future Directions.

Real-world data (RWD) and real-world evidence (RWE) have garnered great interest for supporting drug research and development (R&D) by medical researchers and regulators in recent years. The application and development of RWD/E in drug regulatory decision-making have been vigorously promoted in China. This study seeks to provide a broad overview of how RWE has been contributing to drug regulatory decisions in China. In this paper, we review the development of RWD and RWE, summarize key elements that promote application of RWE, introduce relevant methods and guidelines, elaborate on the opportunities and challenges of RWE in regulatory decision-making in China, and put forward suggestions to promote the application of RWE in China's regulatory decision-making and to further facilitate innovative drug evaluation and regulation.

Assessment of efficacy of drug evaluation and classification program in Florida.

OBJECTIVE: The present study aims to assess the effectiveness of the Drug Evaluation and Classification (DEC) program in Florida. METHODS: Data from 236 completed DEC evaluations of central nervous system (CNS) depressants, CNS stimulants, narcotic analgesics, and cannabis were analyzed using a classification process comprising toxicology findings and corresponding Drug Recognition Expert (DRE) opinions. A series of standard measures (sensitivity, specificity, false-alarm rate, miss rate, corroboration, and accuracy) were calculated to assess the effectiveness of the DEC program. RESULTS: DREs provided 172 correct opinions and 23 missed opinions, resulting in an accuracy rate of 88%, sensitivity rate of 97%, specificity rate of 23%, false alarm rate of 77%, miss rate of 3%, and corroboration rate of 91%. The 12-step DRE protocol of the DEC program therefore has the desired effect of DREs formulating correct opinions. The specificity and false alarm rate were influenced by the restricted testing procedures in the state of Florida. In general, law enforcement officers certified in the DEC program with specialized training can identify drugged drivers and the correct drug category of the drug causing impairment at the time of operating a vehicle. The DEC program goals are met through rigorous training and a curriculum establishing the 12-step DRE protocol. CONCLUSIONS: DRE drug classification opinions identify drugged drivers. The limitations of Florida's biological sample testing procedures have an impact on the specificity of DRE opinions. Addressing these limitations could increase the confirmation rates of the presence of drugs in the individual's biological samples, which would directly impact the conviction rates in DUI-related criminal cases. Further Florida's testing procedures need to be further studied and updated to improve the DEC program in Florida.

Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study.

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

θ-Nanopipette for Single-Cell Resistive-Pulse Profiling of DNA Repair Proteins Accompanied by Drug Evaluation.

Single-cell analysis of the DNA repair protein is important but remains unachieved. Exploration of nanopipettte technologies in single-cell electroanalysis has recently seen rapid growth, while the θ-nanopipette represents an emerging technological frontier with its potential largely veiled. Here a θ-nanopipette is first applied for single-cell resistive-pulse sensing (RPS) of the important DNA repair protein O6-alkylguanine DNA alkyltransferase (hAGT). The removal of alkyl mutations by hAGT could restore the damaged aptamer linking with a structural DNA carrier, allowing the selective binding of the aptamer to thrombin with precisely matched size to produce distinct RPS signals when passing through the orifice. Kinetic analysis of hAGT repair was studied. Meanwhile, the device shows the simultaneous on-demand infusion of inhibitors to inactivate the hAGT activity, indicative of its potential in drug screening for enhanced chemotherapy. This work provides a new paradigm for θ-nanopipette-based single-cell RPS of a DNA repair protein accompanied by drug evaluation.

Organ-on-a-chip meets artificial intelligence in drug evaluation.

Drug evaluation has always been an important area of research in the pharmaceutical industry. However, animal welfare protection and other shortcomings of traditional drug development models pose obstacles and challenges to drug evaluation. Organ-on-a-chip (OoC) technology, which simulates human organs on a chip of the physiological environment and functionality, and with high fidelity reproduction organ-level of physiology or pathophysiology, exhibits great promise for innovating the drug development pipeline. Meanwhile, the advancement in artificial intelligence (AI) provides more improvements for the design and data processing of OoCs. Here, we review the current progress that has been made to generate OoC platforms, and how human single and multi-OoCs have been used in applications, including drug testing, disease modeling, and personalized medicine. Moreover, we discuss issues facing the field, such as large data processing and reproducibility, and point to the integration of OoCs and AI in data analysis and automation, which is of great benefit in future drug evaluation. Finally, we look forward to the opportunities and challenges faced by the coupling of OoCs and AI. In summary, advancements in OoCs development, and future combinations with AI, will eventually break the current state of drug evaluation.

Microvascularized tumor assembloids model for drug delivery evaluation in colorectal cancer-derived peritoneal metastasis.

Peritoneal metastasis (PM) is a fatal state of colorectal cancer, and only a few patients may benefit from systemic chemotherapy. Although hyperthermic intraperitoneal chemotherapy (HIPEC) brings hope for affected patients, the drug development and preclinical evaluation of HIPEC are seriously lagging behind, mainly due to the lack of an ideal in vitro PM model that makes drug development over-reliant on expensive and inefficient animal experiments. This study developed an in vitro colorectal cancer PM model [microvascularized tumor assembloids (vTA)] based on an assembly strategy of endothelialized microvessels and tumor spheroids. Our data showed that the in vitro perfusion cultured vTA could maintain a similar gene expression pattern to their parental xenografts. Also, the drug penetration pattern of the in vitro HIPEC in vTA could mimic the drug delivery behavior in tumor nodules during in vivo HIPEC. More importantly, we further confirmed the feasibility of constructing a tumor burden-controlled PM animal model using vTA. In conclusion, we propose a simple and effective strategy to construct physiologically simulated PM models in vitro, thus providing a basis for PM-related drug development and preclinical evaluation of locoregional therapies. STATEMENT OF SIGNIFICANCE: This study developed an in vitro colorectal cancer peritoneal metastasis (PM) model based on microvascularized tumor assembloids (vTA) for drug evaluation. With perfusion culture, vTA could maintain a similar gene expression pattern and tumor heterogeneity to their parental xenografts. And the drug penetration pattern in vTA was similar to the drug delivery behavior in tumor nodules under in vivo treatment. Moreover, vTA was more conducive to construct PM animal models with controllable tumor burden. In conclusion, the construction of vTA could provide a new strategy for the PM-related drug development and preclinical evaluation of locoregional therapies.

Children's Oncology Group's 2023 blueprint for research: Pharmacy.

Children's Oncology Group (COG) pharmacists and pharmacy technicians from more than 200 COG-member institutions comprise the COG Pharmacy Discipline. Discipline members serve an essential role in the design and execution of COG clinical trials. Core activities include study drug management, study drug access, clinical trial operations, protocol harmonization, and direct patient care. Discipline members are also actively involved in continuing education, membership engagement, and research across other COG committees/domains. Future areas of committed growth for the discipline include pharmacogenomics, pharmacokinetics, pharmacoeconomics, pharmaceutics, and implementation science.

INP104: a drug evaluation of a nonoral product for the acute treatment of migraine.

Migraine is a highly prevalent, disabling neurological disorder that is also associated with gastrointestinal symptoms, autonomic dysfunction and allodynia. Despite the availability of multiple acute agents for migraine, an unmet need remains for effective, well-tolerated drugs that are nonoral and noninvasive. Here, we provide a drug evaluation of INP104, a novel drug-device combination product of dihydroergotamine (DHE) mesylate - a molecule with a long history of efficacy familiar to headache specialists - which is delivered to the difficult-to-reach upper nasal space where it is rapidly and consistently absorbed via Precision Olfactory Delivery (POD®). In clinical trials, INP104 exhibited favorable pharmacokinetics, a well-tolerated safety profile, and rapid symptom relief, highlighting its potential as a suitable acute therapy for migraine.

Migraine is a very common headache disorder that often presents with pain and gastrointestinal symptoms. There are many available treatments for migraine, but some patients still need an option that works well for them, that is noninvasive, or does not need to be taken orally. Here we provide a drug evaluation of INP104, an approved acute treatment for migraine that combines a drug and a device: the medication dihydroergotamine (DHE) mesylate, which has been used for decades for treating acute symptoms of migraine, and the Precision Olfactory Delivery (POD^®) device, which delivers DHE mesylate to the hard-to-reach upper regions of the nose. Targeting this region helps medication to be absorbed faster and more consistently. In clinical trials, INP104 demonstrated favorable drug properties, came with few adverse events, and provided fast relief from migraine symptoms.

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Nano-composite system of traditional Chinese medicine for ocular applications: molecular docking and three-dimensional modeling insight for intelligent drug evaluation.

The absorption of drugs was impeded in the posterior part of the eye due to the special structure. In addition, it was crucial to comprehend transport laws of molecules in ocular drug delivery for designing effective strategies. However, the current quality evaluation methods of the eye were backward and lack of dynamic monitoring of drug processes in vivo. Herein, nano-drug delivery system and three-dimensional (3D) model were combined to overcome the problems of low bioavailability and diffusion law. The model drugs were screened by molecular docking. The flexible nano-liposome (FNL) and temperature-sensitive gel (TSG) composite formulation was characterized through comprehensive evaluation. COMSOL software was utilized to build 3D eyeball to predict the bioavailability of drugs. The size of the preparation was about 98.34 nm which is relatively optimal for the enhanced permeability of the eyes. The formulation showed a stronger safety and non-irritant. The pharmacokinetics results of aqueous humor showed that the AUC of two drugs in this system increased by 3.79 and 3.94 times, respectively. The results of 3D calculation model proved that the concentrations of drugs reaching the retina were 1.90×10-5 mol/m3 and 6.37×10-6 mol/m3. In conclusion, the FNL-TSG markedly improved the bioavailability of multiple components in the eye. More importantly, a simplified 3D model was developed to preliminarily forecast the bioavailability of the retina after drug infusion, providing technical support for the accurate evaluation of ocular drug delivery. It provided new pattern for the development of intelligent versatile ophthalmic preparations.