Enriched Pharmacokinetic Behavior and Antitumor Efficacy of Thymoquinone by Liposomal Delivery

Rachamalla, Hari Krishnareddy; Bhattacharya, Santanu; Ahmad, Ajaz; Sridharan, Kathyayani; Madamsetty, Vijay Sagar; Mondal, Sujan Kumar; Wang, Enfeng; Dutta, Shamit K.; Jan, Basit L.; Jinka, Sudhakar; Jaggarapu, Madan Mohan Chandra Sekhar; Yakati, Venu; Mukhopadhyay, Debabrata; Alkharfy, Khalid M.; Banerjee, Rajkumar

doi:10.2217/nnm-2020-0470

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…Additionally, a cationic liposomal formulation of TQ displayed significantly higher in vivo absorption, approximately 1.5-fold higher plasma concentration, greater bioavailability, decreased volume of distribution and improved clearance relative to TQ [ 68 ]. Moreover, a self-nanoemulsifying drug delivery system was designed using the microemulsifcation technique.…”

Section: Resultsmentioning

confidence: 99%

Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review

Mahomoodally

Aumeeruddy²,

Legoabe³

et al. 2022

IJMS

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Despite existing conventional hypoglycemic drugs to manage diabetes, their non-availability and cost in low-income countries coupled with the associated side effects remain a major concern. Consequently, exploring for alternative treatments to manage diabetes has been a continuous priority. Nigella sativa L. (NS) (Family: Ranunculaceae) is regarded as a valuable traditional remedy in diabetes management and extensively studied for its biological properties. This systematic review provides a comprehensive and critical analysis of clinical studies on the efficacy, safety, and mechanism of action of NS and its compound thymoquinone (TQ) in diabetes management. The main scientific databases which were scrutinised were Scopus, PubMed, Google Scholar, and Web of Science. Data search was conducted from inception to January 2022. A total of 17 clinical studies were obtained; 16 studies on Nigella sativa L. and 1 study on its compound TQ. N. sativa was found to be highly potent in terms of its hypoglycemic activity when compared to placebo based on improvement in parameters including fasting blood glucose (FBG), postprandial blood glucose (PPBG), Hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and homeostatic model assessment for assessment of beta-cell functionality (HOMA-β). The compound TQ in combination with a daily dose of metformin demonstrated a greater reduction in the levels of HbA1c and blood glucose compared to metformin alone. The bioavailability of TQ can be enhanced by using nanoparticulate drug delivery systems. Considering the findings of the clinical studies along with negligible adverse effects, NS has strong potential application in bioproduct development for the management of diabetes. Further investigations should explore the detailed mechanism of actions by which TQ exerts its therapeutic antidiabetic effects to provide more insights into its clinical use in the management of diabetes.

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Section: Resultsmentioning

confidence: 99%

Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review

Mahomoodally

Aumeeruddy²,

Legoabe³

et al. 2022

IJMS

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“…These TQ analogs can further effectively inhibit the activity of the COX-1 and COX-2 enzymes, improve the activity of caspase-3, and release cytochrome c. In terms of sensitivity to oxaliplatin and GEM, the TQ analogs TQ-2G and TQ-5A1 have shown better effects than TQ-4A1 and are also better than the parent TQ at enhancing sensitivity to chemotherapeutic drugs ( 51 ). Another study found that TQ combined with D1T (a cationic liposome preparation of TQ) as the carrier could achieve a greater absorption rate, higher plasma concentration and bioavailability, smaller distribution volume, and easier clearance in vivo , which significantly improve its inhibitory effects on pancreatic tumors ( 52 ).…”

Section: Tq Analogs and Carriersmentioning

confidence: 99%

Advances in research on the relationship between thymoquinone and pancreatic cancer

Zhao

Liu

et al. 2023

Front. Oncol.

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Pancreatic cancer has one of the worst prognoses among the most common cancers in the world. Its characteristics include a high rate of metastasis and chemotherapeutic resistance, which present major challenges to the medical community. The potential anticancer effects of thymoquinone (TQ), which is the main bioactive compound of the black seeds of the Nigella sativa plant, have recently received widespread attention for their potential use in treating pancreatic cancer. TQ can inhibit cell proliferation, promote cancer cell apoptosis, inhibit cell invasion and metastasis, enhance chemotherapeutic sensitivity, inhibit angiogenesis, and exert anti-inflammatory effects. These anticancer effects predominantly involve the nuclear factor (NF)-κB, phosphoinositide 3 kinase (PI3K)/Akt, Notch, transforming growth factor (TGF)-β, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways as well as the regulation of the cell cycle, matrix metallopeptidase (MMP)-9 expression, and pyruvate kinase isozyme type M2 (PKM2) activity. TQ regulates the occurrence and development of pancreatic cancer at multiple levels and through multiple targets that communicate with each other. In this review, we summarize and discuss the analogs and carriers of TQ that have been developed in recent years. Given its multilevel anticancer effects, TQ may become a new therapeutic drug for treating pancreatic cancer in the future. This review presents a brief introduction to the research that has been conducted on TQ in relation to pancreatic cancer to provide a theoretical basis for future studies on the topic.

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Approaches to Address PK-PD Challenges of Conventional Liposome Formulation with Special Reference to Cancer, Alzheimer's, Diabetes, and Glaucoma: An Update on Modified Liposomal Drug Delivery System

Kesharwani

Gururani

Jain

et al. 2022

CDM

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Liposomes nowadays have become preferential drug delivery system, since it provides facilitating properties to drugs such as improved therapeutic index of encapsulated drug, target and controlled drug delivery, and less toxicity. However, conventional liposomes have shown some disadvantages such as less drug loading capacity, poor retention, clearance by kidney or reticuloendothelial system, and less release of hydrophilic drugs. Thus, to overcome these disadvantages recently, scientists have explored new approaches and methods viz. ligand conjugation, polymer coating, and liposomes-hybrid including surface-modified liposomes, biopolymer-incorporated liposomes, guest-in-cyclodextrin-in-liposome, liposome-in-hydrogel, liposome-in-film, and liposome-in-nanofiber, etc. These approaches have been shown to improve the physiochemical and pharmacokinetic properties of encapsulated drugs. Lately, Pharmacokinetic-pharmacodynamic (PK–PD) computational modeling has emerged as a beneficial tool for analyzing the impact of formulation- and system-specific factors on the target disposition and therapeutic efficacy of liposomal drugs. There has been an increasing number of liposome-based therapeutic drugs, both FDA approved and undergoing clinical trials having application in anticancer, Alzheimer's, diabetes, and glaucoma. To meet the continuous demand of health sectors and to produce the desired product, it is important to perform pharmacokinetic studies. This review focuses on the physical, physicochemical, and chemical factors of drugs that influence the target delivery of drugs. It also explains various physiological barriers such as systemic clearance, and extravasation. A novel approach, liposomal-hybrid complex: an innovative approach as a vesicular drug delivery system to overcome limited membrane permeability and bioavailability has been discussed in the review. Moreover, this review highlights the pharmacokinetic considerations and challenges of poorly absorbed drugs along with the applications of a liposomal delivery system in improving PKPD in various diseases such as cancer, Alzheimer's, diabetes, and glaucoma.

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Enriched Pharmacokinetic Behavior and Antitumor Efficacy of Thymoquinone by Liposomal Delivery

Cited by 4 publications

References 34 publications

Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review

Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review

Advances in research on the relationship between thymoquinone and pancreatic cancer

Approaches to Address PK-PD Challenges of Conventional Liposome Formulation with Special Reference to Cancer, Alzheimer's, Diabetes, and Glaucoma: An Update on Modified Liposomal Drug Delivery System

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