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姜黄素脂质体目前临床研究进展如何？
姜黄素脂质体在多种疾病的治疗中展现出潜力，尤其是在癌症和糖尿病相关并发症方面，目前已有多项临床研究对其安全性、耐受性、药代动力学及初步疗效进行了评估和探索 。尽管姜黄素脂质体具有改善姜黄素生物利用度的优势，但其在临床转化和广泛应用中仍面临挑战 。
1. 癌症治疗领域的临床研究进展
姜黄素脂质体在多种癌症模型中表现出抗肿瘤活性，其临床研究主要集中在以下几个方面：
- 实体瘤患者的安全性与耐受性
- 静脉给药：一项针对转移性癌症患者的I期剂量递增研究评估了静脉注射脂质体姜黄素（Lipocurc）的安全性、耐受性及抗肿瘤活性 。研究结果显示，在26名接受100至300 mg/m²剂量（输注8小时）的患者中未观察到剂量限制性毒性。然而，在6名接受300 mg/m²剂量（输注6小时）的患者中，有1名出现溶血，另有3名患者血红蛋白下降超过2 g/dL，但无溶血迹象。该研究得出结论，300 mg/m²脂质体姜黄素在6小时内输注是这些经过大量预治疗患者的最大耐受剂量，并被推荐作为抗癌临床试验的起始剂量 。另一项在健康受试者中进行的I期临床试验也探究了静脉注射脂质体姜黄素的药代动力学、安全性和耐受性 。研究发现，剂量依赖性地增加了姜黄素及其代谢物四氢姜黄素（THC）的血浆浓度。药物输注结束后，姜黄素和THC的血浆浓度在6-60分钟内迅速下降至低于定量限。平均尿排泄量约为总系统清除率的0.1%。脂质体姜黄素耐受性良好，但在剂量≥120 mg/m²时观察到红细胞棘形细胞形成并伴随平均细胞体积增加，这可能代表剂量限制性毒性迹象 。
- 胸膜腔内给药：针对恶性胸腔积液（MPE）患者，一项I期、开放标签、单中心、非对照、剂量递增研究（IPAL-MPE）正在评估通过现有隧道式留置胸膜导管（TIPC）直接向肿瘤部位单次给药脂质体姜黄素的可行性、耐受性和药代动力学特征 。主要目的是确定最大耐受剂量。研究计划采用3+3扩展队列设计，剂量队列包括100、200和300 mg/m²。这项研究将有助于探索姜黄素脂质体局部给药在减轻MPE症状和改善患者生活质量方面的潜力 。
- 抗肿瘤活性与挑战
- 虽然在临床试验中未检测到通过RECIST V1.1评估的显著抗肿瘤活性，但在两名患者中观察到肿瘤标志物显著反应和短暂的临床益处 。这提示姜黄素脂质体可能存在一定的抗肿瘤作用，但需要进一步研究和更优化的给药方案。
- 姜黄素脂质体在乳腺癌和胶质母细胞瘤等癌症治疗中显示出巨大潜力，因为它们能够改善姜黄素的体内稳定性和生物利用度，并促进对肿瘤病灶的精确靶向 。然而，目前关于纳米姜黄素应用于乳腺癌诊断和在乳腺癌患者中临床转化的研究仍然有限 。对于胶质母细胞瘤，姜黄素的临床应用受限于低水溶性、低生物利用度、快速全身清除和较差的血脑屏障（BBB）渗透性，而纳米载体系统（包括脂质体）的开发旨在克服这些挑战，提高姜黄素在胶质瘤微环境中的积累 。
- 前列腺癌的治疗也面临耐药性和累积毒性问题，姜黄素和胡椒碱的纳米制剂（包括脂质体）被提出作为潜在的新疗法，以克服其生物利用度差和快速代谢的局限性 。然而，临床转化仍面临依赖被动靶向、生产可扩展性不足等障碍。专家建议未来的成功取决于从“烧杯”合成转向微流控生产（质量源于设计）以及采用主动靶向（如PSMA靶向递送）以渗透前列腺基质 。
2. 糖尿病及并发症治疗领域的临床研究进展
姜黄素在对抗糖尿病及其并发症（如糖尿病伤口愈合、糖尿病动脉粥样硬化、糖尿病脑病）方面显示出多靶点机制的潜力 。脂质体等新型制剂旨在克服其溶解度和生物利用度差的限制 。
- 糖尿病牙周炎：一项临床研究评估了姜黄素脂质体缓释凝胶对糖尿病牙周炎患者牙周缺损的疗效，从临床和生化角度进行评估 。研究将30名糖尿病牙周炎患者随机分为三组，并设10名健康对照组。其中一组患者接受了刮治和根面平整（SRP）并应用了姜黄素脂质体缓释凝胶。结果显示，所有治疗组在临床和生化参数上均有统计学显著的改善，其中姜黄素脂质体缓释凝胶组改善最显著，其次是姜黄素凝胶组和安慰剂凝胶组 。结论认为，姜黄素脂质体缓释凝胶增强了抗氧化能力，降低了炎症介质，并显著改善了糖尿病牙周炎患者的临床结局 。
3. 姜黄素脂质体存在的普遍挑战
尽管姜黄素脂质体在临床前和早期临床试验中显示出希望，但姜黄素本身固有的局限性（如低水溶性、低生物利用度、快速代谢和全身清除）仍然是其广泛临床应用的主要障碍 。脂质体和其他纳米载体系统虽然在一定程度上克服了这些挑战，改善了姜黄素的溶解度、稳定性、系统循环和靶向递送，但纳米载体的利用仍处于初始阶段，监管审批尚未完成，并且其使用仍存在安全隐患 。
- 药代动力学问题：即使是脂质体姜黄素，在静脉输注结束后，其血浆浓度也可能迅速下降至不可检测水平 。这提示需要进一步优化剂型以实现更持久的药物暴露或更有效的靶向递送。
- 剂量限制性毒性：在某些情况下，高剂量的脂质体姜黄素可能引起红细胞形态改变或溶血，这需要进一步研究其机制并确定安全的剂量范围 。
- 临床转化障碍：研究文献中关于纳米姜黄素在乳腺癌诊断和患者中临床转化的研究仍然有限 。此外，纳米载体在姜黄素递送方面的利用仍处于初始阶段，尚待监管批准，并且对其安全性仍存在持续担忧 。未来研究应侧重于开发具有表面修饰、高载药量、生物降解性、相容性和自主靶向特异性和选择性的纳米载体 。
- 临床试验不足：目前关于纳米姜黄素的临床研究相对有限，尤其是针对特定癌症类型的动物模型研究和来自制药行业的支持不足，阻碍了基于姜黄素的癌症预防策略的进一步发展 。
总结
姜黄素脂质体作为一种有前景的药物递送系统，在改善姜黄素的药代动力学和生物利用度方面取得了显著进展，并在肿瘤和糖尿病并发症等领域开展了初步的临床研究 。早期的I期临床试验主要集中在评估其安全性、耐受性，并探索药代动力学特征，结果表明在一定剂量范围内是安全的，但高剂量可能出现剂量限制性毒性 。尽管在癌症治疗中直接的抗肿瘤活性证据有限，但在一些患者中观察到生物学反应 。在糖尿病相关牙周炎的治疗中，姜黄素脂质体显示出改善临床和生化参数的积极效果 。
然而，姜黄素脂质体在临床转化中仍面临诸多挑战，包括需要更优化的制剂以实现更持久的疗效、克服局部递送的障碍、以及解决纳米载体的长期安全性和监管审批问题 。未来的研究需要更深入地探索靶向递送策略，开展更大规模、设计严谨的临床试验，以充分评估姜黄素脂质体在各种疾病治疗中的确切疗效和安全性，并促进其从实验室走向临床实践 。
References
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Md Ataur Rahman, Mahesh Kumar Yadab, Meser M Ali
Glioblastoma (GBM), the most common, invasive, and chemoresistant form of adult primary brain cancer, is characterized by rapid cell proliferation, local invasiveness, and resistance to chemotherapy (e.g., temozolomide (TMZ)) and radiation therapy. Curcumin, a bioactive polyphenol derived from , has exhibited exceptional anti-cancer properties, including anti-proliferative, pro-apoptotic, anti-inflammatory, and anti-angiogenic activities in a wide range of cancer models, including GBM. However, the clinical application of curcumin has been seriously limited by several challenges, including low water solubility, low bioavailability, rapid systemic clearance, and poor blood-brain barrier (BBB) penetration. To overcome these challenges, several nanocarrier systems to produce nanocurcumin have been developed, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, and micelles. These nanoformulations improve the solubility, stability, systemic circulation, and target-directed delivery of curcumin to glioma cells, thereby resulting in a high level of accumulation in the glioma microenvironment. On the other hand, this work is devoted to the potential of curcumin and nanocurcumin for the treatment of GBM. The article provides a detailed review of the major molecular targets of curcumin, such as NF-κB, STAT3, PI3K/AKT/mTOR, and p53 signaling pathways, as well as recent advancements in nanotechnology-based delivery platforms that improve drug delivery across the BBB and their possible clinical translation. We also include a thorough examination of the issues, limitations, and potential opportunities associated with the clinical advancement of curcumin-based therapeutics for GBM.
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Preetha Anand, Ajaikumar B Kunnumakkara, Robert A Newman, et al.
Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.
3Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans.PubMed
Angela Storka, Brigitta Vcelar, Uros Klickovic, et al.
INTRODUCTION: Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects. MATERIAL AND METHODS: 50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously. RESULTS: Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages ≥ 120 mg/m2. CONCLUSION: Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.
4Curcumin and nanodelivery systems: New directions for targeted therapy and diagnosis of breast cancer.PubMed
Yao Zhou, Jie Gong, Xianguang Deng, et al.
As the global incidence of breast cancer continues to surge, the pursuit of novel, low-toxicity, and highly efficacious therapeutic strategies has emerged as a pivotal research focus. Curcumin (CUR), an active constituent of traditional Chinese medicine (TCM) renowned for its antimicrobial, anti-inflammatory, antioxidant, and antitumor properties, exhibits immense potential in breast cancer therapy. Nevertheless, CUR's poor water solubility, chemical instability, and unfavorable pharmacokinetics have impeded its clinical utilization. To address these challenges, nano-delivery systems have been extensively exploited for CUR administration, enhancing its in vivo stability and bioavailability, and facilitating precise targeting of breast cancer lesions. Therefore, we elaborate on CUR's chemical foundations, drug metabolism, and safety profile, and elucidate its potential mechanisms in breast cancer therapy, encompassing inducing apoptosis and autophagy, blocking cell cycle, inhibiting breast cancer metastasis, regulating tumor microenvironment and reversing chemotherapy resistance. The review primarily emphasizes recent advancements in CUR-based nano-delivery systems for the treatment and diagnosis of breast cancer. Liposomes, nanoparticles (encompassing polymer nanoparticles, solid lipid nanoparticles, mesoporous silica particles, metal/metal oxide nanoparticles, graphene nanomaterials, albumin nanoparticles, etc.), nanogels, and nanomicelles can serve as delivery carriers for CUR, exhibiting promising anti-breast cancer effects in both in vivo and in vitro experiments. Furthermore, nano-CUR can be integrated with fluorescence imaging, magnetic resonance imaging, computed tomography imaging, ultrasound, and other techniques to achieve precise localization and diagnosis of breast cancer masses. While this article has summarized the clinical studies of nano-curcumin, it is noteworthy that the research literature on nano-CUR applied to breast cancer diagnosis and the translation of nano-CUR clinical studies in BC patients remain limited. Therefore, future research should intensify exploration in this direction.
5Recent updates in curcumin delivery.PubMed
Mohammad A Obeid, Manal Alsaadi, Alaa A Aljabali
Curcumin is a natural component extracted from the rhizomes of turmeric (), a natural plat with known medicinal uses for more than 4000 years. Most turmeric therapeutic effects are attributed to curcumin, a yellow-coloured extract. Curcumin has received considerable attention due to its biological activities, such as its use in arthritis, liver and neurodegenerative diseases, obesity, and several types of cancers. Most of these curcumin therapeutic activities are related to its antioxidant and anti-inflammatory effects. However, the clinical application of curcumin is hampered by some limitations that prevent its extensive clinical application. Curcumin high hydrophobicity of curcumin and limited water solubility are among the most important limitations. This poor solubility will result in low bioavailability due to its poor absorption into plasma and the target tissues. Curcumin also has rapid metabolism, which will significantly lower its bioavailability and shorten its half-life. Moreover, curcumin is photosensitive with limited chemical stability during manufacturing and storage. These limitations have been overcome by applying nanotechnology using several types of nanoparticles (NPs). This includes using NPs such as liposomes, niosomes, gold nanoparticles, and many others to improve the curcumin solubility and bioavailability. This review focuses on the different types of NPs investigated and the outcomes generated by their use in the most recent studies in this field. To follow the latest advances in the field of site-specific drug delivery using nanomaterials, an electronic databases search was conducted using PubMed, Google scholar and Scopus using the following keywords: lipid-based nanoparticles, curcumin delivery, niosomes, and liposomes.
6Manganese superoxide dismutase in cancer prevention.PubMed
Delira Robbins, Yunfeng Zhao
SIGNIFICANCE: Cancer is the second leading cause of death in the United States. Considering the quality of life and treatment cost, the best way to fight against cancer is to prevent or suppress cancer development. Cancer is preventable as indicated by human papilloma virus (HPV) vaccination and tamoxifen/raloxifen treatment in breast cancer prevention. The activities of superoxide dismutases (SODs) are often lowered during early cancer development, making it a rational candidate for cancer prevention. RECENT ADVANCES: SOD liposome and mimetics have been shown to be effective in cancer prevention animal models. They've also passed safety tests during early phase clinical trials. Dietary supplement-based SOD cancer prevention provides another opportunity for antioxidant-based cancer prevention. New mechanistic studies have revealed that SOD inhibits not only oncogenic activity, but also subsequent metabolic shifts during early tumorigenesis. CRITICAL ISSUES: Lack of sufficient animal model studies targeting specific cancers; and lack of clinical trials and support from pharmaceutical industries also hamper efforts in further advancing SOD-based cancer prevention. FUTURE DIRECTIONS: To educate and obtain support from our society that cancer is preventable. To combine SOD-based therapeutics with other cancer preventive agents to obtain synergistic effects. To formulate a dietary supplementation-based antioxidant approach for cancer prevention. Lastly, targeting specific populations who are prone to carcinogens, which can trigger oxidative stress as the mechanism of carcinogenesis.
7A phase 1 dose-escalation study on the safety, tolerability and activity of liposomal curcumin (Lipocurc) in patients with locally advanced or metastatic cancer.PubMed
Richard Greil, Sigrun Greil-Ressler, Lukas Weiss, et al.
PURPOSE: This study was conducted to investigate the safety and tolerability of increasing doses of liposomal curcumin in patients with metastatic cancer. Investigations of anti-tumor activity and of the pharmacokinetics of curcumin were secondary objectives. METHODS: In this phase I, single-center, open-label study in patients with metastatic tumors, liposomal curcumin was administered as a weekly intravenous infusion for 8 weeks. Dose escalation was started at 100 mg/m over 8 h and the dose increased to 300 mg/m over 6 h. RESULTS: 32 patients were treated. No dose-limiting toxicity was observed in 26 patients at doses between 100 and 300 mg/m over 8 h. Of six patients receiving 300 mg/m over 6 h, one patient developed hemolysis, and three other patients experienced hemoglobin decreases > 2 g/dL without signs of hemolysis. Pharmacokinetic analyses revealed stable curcumin plasma concentrations during infusion followed by rapid declines to undetectable levels after the infusion. Anti-tumor activity by RECIST V1.1 was not detected. Significant tumor marker responses and transient clinical benefit were observed in two patients. CONCLUSION: 300 mg/m liposomal curcumin over 6 h was the maximum tolerated dose in these heavily pretreated patients, and is the recommended starting dose for anti-cancer trials.
8Study protocol of a phase 1 clinical trial establishing the safety of intrapleural administration of liposomal curcumin: curcumin as a palliative treatment for malignant pleural effusion (IPAL-MPE).PubMed
Ashleigh Jean Hocking, Alexandra L Farrall, Sarah Newhouse, et al.
INTRODUCTION: This is a phase 1, open-label, single-centre, uncontrolled, dose-escalation study to evaluate the feasibility, tolerability and pharmacokinetic profiles of a single dose of liposomal curcumin, administered via an existing tunnelled indwelling pleural catheter (TIPC) directly to the tumour site in individuals with diagnoses of malignant pleural effusion. Primarily, we aim to determine a maximum tolerated dose of liposomal curcumin administered via this method. METHODS AND ANALYSIS: We will use a 3+3 expanded cohort for predefined dose-escalation levels or until a predefined number of dose-limiting toxicities are reached. Participants will be administered a single dose of liposomal curcumin (LipoCurc, SignPath Pharma) via their existing TIPC as a sequential enrolling case series with the following dose cohorts: 100, 200 and 300 mg/m. Primary endpoints are determination of the maximum tolerated dose within the predetermined dose range, and determination of the feasibility of intrapleural administration of liposomal curcumin via an existing TIPC. Secondary endpoints include determination of the safety and tolerability of intrapleural administration of liposomal curcumin, median overall survival, effects on quality of life and on feelings of breathlessness, and the pharmacokinetics and concentrations of curcumin from the plasma and the pleural fluid. Important inclusion criteria include age ≥18 years, an existing TIPC, a pleural biopsy or pleural fluid cytology-proven diagnosis of malignant pleural effusion and for whom no antitumour therapy of proven benefit is available or has been previously declined, eastern cooperative group performance status <2. ETHICS AND DISSEMINATION: The study protocol has been approved by the Southern Adelaide Local Health Network Human Research Ethics Committee (HREC) (approval number: HREC/20/SAC/11). Study results will be published in peer-reviewed journals, and presented at conferences, in field of medical oncology and respiratory medicine. TRIAL REGISTRATION NUMBER: ACTRN12620001216909. PROTOCOL VERSION NUMBER: V.1.0.
9Curcumin and its novel formulations for diabetes mellitus and its complications: a review.PubMed
Xiaoqin Liu, Qingzhi Liang, Wei Jiang, et al.
Diabetes mellitus (DM), a growing global health crisis, drives demand for safe, effective therapies. Curcumin (CUR), a turmeric-derived polyphenol, shows promise in combating DM and its complications (such as diabetic wound healing (DWH), diabetic atherosclerosis (DA), and diabetic encephalopathy (DE)) multi-target mechanisms. Despite its efficacy and low toxicity, CUR's clinical application is hindered by poor solubility and bioavailability. Recent advances in novel formulations (such as nanoparticles and liposomes) aim to overcome these limitations. This review summarizes CUR's therapeutic mechanisms, highlights cutting-edge delivery systems developed over 20 years, and identifies key challenges in translation. By bridging preclinical insights with formulation innovations, we provide a roadmap for optimizing CUR-based therapies, accelerating their clinical adoption for DM management.
10Nanotechnology and curcumin: a novel and promising approach in digestive cancer therapy.PubMed
Yi Zhang, Zheng Li, Ying Huang, et al.
This study reviews the application of nanotechnology and curcumin, a polyphenol extracted from turmeric, in treating digestive cancers, one of the most common types of malignancies worldwide. Despite curcumin's potential for inhibiting tumor growth, its clinical application is hindered by issues such as poor solubility and bioavailability. Nanomedicine, with its unique ability to enhance drug delivery and reduce toxicity, offers a solution to these limitations. The paper focuses on the development of nanoformulations of curcumin, such as nanoparticles and liposomes, that improve its bioavailability and efficacy in treating digestive cancers, including liver and colorectal cancers. The study serves as a valuable reference for future research and development in this promising therapeutic approach.
11Obstacles against the Marketing of Curcumin as a Drug.PubMed
Kambiz Hassanzadeh, Lucia Buccarello, Jessica Dragotto, et al.
Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb , has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it's interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug.
12Advances in Nanocarrier Systems for Overcoming Formulation Challenges of Curcumin: Current Insights.PubMed
Shery Jacob, Fathima Sheik Kather, Mohamed A Morsy, et al.
Curcumin, an organic phenolic molecule that is extracted from the rhizomes of Linn, has undergone extensive evaluation for its diverse biological activities in both animals and humans. Despite its favorable characteristics, curcumin encounters various formulation challenges and stability issues that can be effectively addressed through the application of nanotechnology. Nano-based techniques specifically focused on enhancing solubility, bioavailability, and therapeutic efficacy while mitigating toxicity, have been explored for curcumin. This review systematically presents information on the improvement of curcumin's beneficial properties when incorporated, either individually or in conjunction with other drugs, into diverse nanosystems such as liposomes, nanoemulsions, polymeric micelles, dendrimers, polymeric nanoparticles, solid-lipid nanoparticles, and nanostructured lipid carriers. Additionally, the review examines ongoing clinical trials and recently granted patents, offering a thorough overview of the dynamic landscape in curcumin delivery. Researchers are currently exploring nanocarriers with crucial features such as surface modification, substantial loading capacity, biodegradability, compatibility, and autonomous targeting specificity and selectivity. Nevertheless, the utilization of nanocarriers for curcumin delivery is still in its initial phases, with regulatory approval pending and persistent safety concerns surrounding their use.
13Recent progress in studying curcumin and its nano-preparations for cancer therapy.PubMed
Jieying Liu, Siyuan Chen, Li Lv, et al.
A hydrophobic polyphenol compound extracted from turmeric, curcumin has been widely utilized as traditional medicines for centuries in China and India. Over the last decades, because of its low toxicity, extensive studies have been focused on its physicochemical properties and pharmacological activities on various diseases, such as cancer, cardio-vascular disease, inflammatory bowel, wound healing, Alzheimer's disease, rheumatoid arthritis, and diabetes. In particular, bioactivities of curcumin as an effective chemopreventive agent, chemo-/radio-sensitizer for tumor cells, and chemo-/radio-protector for normal organs, are of extraordinary research interests in the literature. Despite these advantages, applications of curcumin are limited in clinical trials because of its poor water solubility and low oral bioavailability. Nano-preparations as an emerging platform for the efficient delivery of anti-cancer drugs should overcome these problems. In this review, we at first briefly revisit important properties of curcumin as well as its uses in cancer treatments, and then overview various nano-preparations of curcumin for cancer therapy, including nanoparticles, liposomes, micelles, nanoemulsions, cyclodextrin complexes, nanodisks, nanofibres, solid lipid nanoparticles, and curcumin conjugates.
14Curcumin and its formulations: potential anti-cancer agents.PubMed
Jun-Ling Ji, Xian-Feng Huang, Hai-Liang Zhu
Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L. Extensive research over the last half century has revealed that curcumin can inhibit the proliferation of various tumor cells in culture, prevent carcinogen induced cancers in rodents and inhibit the growth of human tumors in xenotransplant or orthotransplant animal models. Several phase I and phase II clinical trials indicated that curcumin is quite safe and may exhibit therapeutic efficacy. The utility of curcumin is limited by its lack of water solubility and relatively low in vivo bioavailability. Multiple approaches including nanoparticles, liposomes, micelles and phospholipid complexes are being sought to overcome these limitations. This review describes the general properties of curcumin and its potential effect against cancer including evidences of its antitumor action in vitro, in vivo, clinically and the strategies to overcome its low bioavailability.
15Curcumin - Bioavailability Enhancement by Prodrug Approach and Novel Formulations.PubMed
Narsaiah Chelimela, Rajasekhar Reddy Alavala, Shobha Rani Satla
Curcumin is a diverse natural pharmacological agent involved in various signal transduction mechanisms. Therapeutically, this potent molecule faces different challenges and issues related to low bioavailability due to its poor aqueous solubility, less permeability, faster elimination and clearance. Experts in synthetic chemistry and pharmaceuticals are continuously sparing their efforts to overcome these pharmacokinetic challenges by using different structural modification strategies and developing novel drug delivery systems. In this mini-review article, we are focusing on development of curcumin derivatives by different possible routes like conjugation with biomolecules, natural polymers, synthetic polymers, natural products, metal conjugates and co- administration with natural metabolic inhibitors. In addition to that, it was also focused on the preparation of modified formulations such as micelles, microemulsions, liposomes, complexes with phospholipids, micro and nanoemulsions, solid lipid nanoparticles, nano lipid carriers, biopolymer nanoparticles and microgels to improve the pharmacokinetic properties of the curcumin without altering its pharmacodynamics activity. This review helps to understand the problems associated with curcumin and different strategies to improve its pharmacokinetic profile.
16Advances in lipo-solubility delivery vehicles for curcumin: bioavailability, precise targeting, possibilities and challenges.PubMed
Chaoting Wen, Liyan Cao, Zhenyue Yu, et al.
BACKGROUND: Curcumin (Cur) is a natural pigment containing a diketone structure, which has attracted extensive attention due to its strong functional activities. However, the low solubility and poor stability of Cur limit its low bioavailability and multi-function. It is essential to develop effective measures to improve the unfavorable nature of Cur and maximize its potential benefits in nutritional intervention. SCOPE AND APPROACH: The focus of this review is to emphasize the construction of lipo-solubility delivery vehicles for Cur, including emulsion, nanoliposome and solid liposome. In addition, the potential benefits of vehicles-encapsulated Cur in the field of precise nutrition were summarized, including high targeting properties and multiple disease interventions. Further, the deficiencies and prospects of Cur encapsulated in vehicles for precise nutrition were discussed. KEY FINDINGS AND CONCLUSIONS: The well-designed lipo-solubility delivery vehicles for Cur can improve its stability in food processing and the digestion . To meet the nutritional requirements of special people for Cur-based products, the improvement of the bioavailability by using delivery vehicles will provide a theoretical basis for the precise nutrition of Cur in functional food.
17Enhancing Curcumin Oral Bioavailability Through Nanoformulations.PubMed
Vinod S Ipar, Anisha Dsouza, Padma V Devarajan
Curcumin is a promising therapeutic agent that exhibits manifold therapeutic activities. However, it is challenging to study curcumin as it exhibits poor aqueous solubility and low permeability and it is a substrate for P-glycoprotein (P-gp). It is readily metabolized in the body, but many active metabolites of curcumin have been identified that could also be exploited for therapy. Strategies for the oral bioenhancement of curcumin to leverage the potential of curcumin as a therapeutic molecule are discussed here in light of these challenges. A brief discussion of conventional bioenhancement strategies using cyclodextrin complexes, solid dispersions, and solid self-emulsifying drug delivery systems is given. However, the major focus of this review is the application of nano-based approaches to the bioenhancement of curcumin. A description of the main advantages of nanosystems is followed by a detailed review of various nanosystems of curcumin, including nanosuspensions and various carrier-based nanosystems. Each nanosystem considered here is first briefly introduced, and then studies of the nanosystem containing curcumin are discussed. Lipid-based systems including liposomes and solid lipid nanoparticles, microemulsions, self-microemulsifying drug-delivery systems, nanoemulsions, and polymeric nanoparticles-which are widely explored-are dealt with in detail. Other miscellaneous systems discussed include inorganic nanoparticles, micelles, solid nanodispersions, phytosomes, and dendrimers. The possibility of using intact nanoparticles to achieve the targeted oral delivery of curcumin and thus harness the benefits of this wonder nutraceutical is an exciting prospect.
18Sustained Release of Liposomal Curcumin: Enhanced Periodontal Outcomes in Diabetic Patients.PubMed
Ahmed Abdallah Khalil, Eman Alaaeldin
OBJECTIVE: To evaluate the effect of entrapment of curcumin within liposomal formulation and the sustained release attitude of the formulated liposomal gel on periodontal defects in diabetic patients in clinical and biochemical terms. METHODS: Thirty diabetic patients with periodontitis were randomly assigned to three equal groups and ten healthy participants were assigned as the control group. Group I was subjected to scaling and root planing (SRP) with application of sustained release liposomal curcumin gel. Group II was subjected to scaling and root planning with application of curcumin gel. Group III was subjected to scaling and root planning with application of placebo gel. Group IV (control group), no intervention was done. The following parameters were evaluated before treatment and after 6 and 12 weeks: plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and total antioxidant capacity (TAC). RESULTS: All study groups showed improvement in clinical and biochemical parameters that are statistically significant. Upon comparing the results of treatment modalities, the highest improvement was achieved in group I followed by group II then group III. CONCLUSION: Sustained release liposomal curcumin gel enhanced the antioxidant capacity, decreased the inflammatory mediators and showed more improvement in clinical outcome for treatment of periodontitis in diabetic patients.
19Clinical hurdles for curcumin and piperine nanoparticles in prostate cancer treatment: a bridge too far or a path to clinical reality?PubMed
Jibira Yakubu, Oya Tagit, Amit V Pandey
INTRODUCTION: Prostate cancer (PC) treatment is limited by resistance mechanisms and cumulative toxicities, necessitating novel therapeutic strategies. While curcumin and piperine exhibit potent anticancer properties, their clinical utility is severely compromised by poor bioavailability and rapid metabolism. AREAS COVERED: This review critically analyzes the preclinical and clinical landscape of curcumin and piperine nanoformulations (CPN) for the treatment of PC. We utilized PubMed and Scopus (2000-2025) to evaluate molecular mechanisms, focusing on CYP17A1 inhibition, PI3K/Akt/mTOR signaling, and ferroptosis. The report examines the physicochemical properties of nanocarriers, including PLGA and liposomes, and addresses translational barriers such as the heterogeneity of the Enhanced Permeability and Retention (EPR) effect, stromal density, and risks associated with piperine-mediated drug - drug interactions. EXPERT OPINION: While nano-encapsulation enhances the therapeutic index of curcumin, clinical translation remains stalled by a reliance on passive targeting and insufficient manufacturing scalability. Future success depends on shifting from 'beaker' synthesis to microfluidic production (Quality by Design) and adopting active targeting (e.g. PSMA-directed delivery) to penetrate the prostate stroma. Without these strategic pivots and biomarker-driven trials, CPNs risk remaining an academic curiosity rather than evolving into a viable clinical intervention.