Article
Chemistry, Physical
Vineela Parvathaneni, Rasha S. Elbatanony, Snehal K. Shukla, Nishant S. Kulkarni, Gautam Chauhan, Seyoum Ayehunie, Zhe-Sheng Chen, Aaron Muth, Vivek Gupta
Summary: A cyclodextrin complex of afatinib was developed to enhance its bio-activity and stability, reduce P-gp efflux, and improve its transport across the intestinal membrane. Various studies confirmed the complex formation and physicochemical properties. The complexation significantly increased transport of afatinib across the gut membrane while reducing its efflux ratio, demonstrating its vital role in P-gp efflux modulation.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Yasmeen Cheema, Yusra Sajid Kiani, Kenneth J. J. Linton, Ishrat Jabeen
Summary: Researchers developed a pharmacophore model based on the cryo-EM structure of ABCB1 to screen for new inhibitors, resulting in the identification of six potential inhibitors with distinct chemistries and favorable properties. The compounds exhibited low nanomolar range inhibitory concentrations and two of them were able to resensitize ABCB1-expressing cells to taxol. This study demonstrates the utility of cryo-electron microscopy in drug identification and design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Lara Garcia-Varela, Pascalle Mossel, Pablo Aguiar, Daniel A. Vazquez-Matias, Aren van Waarde, Antoon T. M. Willemsen, Anna L. Bartels, Nicola A. Colabufo, Rudi A. J. O. Dierckx, Philip H. Elsinga, Gert Luurtsema
Summary: This study found that small changes in P-gp function caused by low doses of tariquidar could be detected by [F-18]MC225-K-1 values, confirming the high sensitivity of the radiotracer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Medicinal
I-Ting Wu, Chan-Yen Kuo, Ching-Hui Su, Yu-Hsuan Lan, Chin-Chuan Hung
Summary: This study investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. The results showed that these compounds were not substrates of P-gp and did not affect its expression, but they noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp, leading to the resensitization of MDR cancer cells. Therefore, pinostrobin and tectochrysin are effective P-gp inhibitors and potential candidates for resensitizing MDR cancer cells.
Article
Biochemistry & Molecular Biology
Catia A. Bonito, Ricardo J. Ferreira, Maria-Jose U. Ferreira, Jean-Pierre Gillet, M. Natalia D. S. Cordeiro, Daniel J. V. A. dos Santos
Summary: In this study, the impact of four P-gp mutations on drug-binding and efflux-related signal-transmission mechanism was evaluated. The repacking of the transmembrane helices induced by mutations and ligands indicates P-gp's sensitivity to perturbations in the transmembrane region. Changes in drug-binding were observed as a consequence of transmembrane helices repacking, but were not always correlated with alterations in ligand binding mode and affinity. The changes in drug efflux are mostly related to changes in drug specificity rather than effects on signal-transmission mechanism.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Pharmacology & Pharmacy
Sachin Rathod, Heta Desai, Rahul Patil, Jayant Sarolia
Summary: This article discusses the significance of studying P-glycoprotein in drug delivery and highlights the effective reversal of P-gp inhibition using nonionic surfactants. Nonionic surfactants, being inert, non-toxic, and efficient, show potential as P-gp inhibitors and improve drug absorption and bioavailability through various mechanisms.
Article
Materials Science, Multidisciplinary
Mohamed S. Attia, Mohamed T. Elsebaey, Galal Yahya, Hitesh Chopra, Mohammed A. Marzouk, Ahmed Yahya, Ahmed S. Abdelkhalek
Summary: Drug resistance is a major obstacle in the treatment of chronic diseases, and various approaches have been developed to overcome it, including targeting other factors involved in altered pathways or targeting the resistance factors themselves. P-glycoprotein (P-gp) and multidrug resistance proteins are among the most causative factors for drug resistance. This review focuses on the use of pharmaceutical polymers as P-gp inhibitors and discusses how modifying their properties can affect P-gp's function. Various P-gp inhibitors, such as chitosan, Soluplus (R), Poloxamers, polyethylene glycols, dendrimers, anionic gums, sodium alginate, and other functionalized polymers, show promise as drug delivery tools by interfering with P-gp. Additionally, pharmaceutical polymers have been utilized in different therapies due to their exceptional physicochemical properties, enhancing their bioavailability, antimicrobial activity, and anticancer properties.
MATERIALS TODAY COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dhanamjai Penta, Priya Mondal, Jagadish Natesh, Syed Musthapa Meeran
Summary: The study demonstrates that diindolylmethane can enhance the efficacy of Centchroman in treating breast cancer by modulating drug efflux transporters, inhibiting cell proliferation, inducing apoptosis, and hindering stemness of cancer cells.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Aobulikasimu Hasan, Dan Tang, Dilaram Nijat, Hequn Yang, H. A. Aisa
Summary: The study isolated several new diterpenoids from Euphorbia glomerulans, with compound 5 showing high efficacy in reversing multidrug resistance in cancer by inhibiting P-gp transport function. Molecular docking predicted the recognition mechanism of compound 5 and verapamil with P-gp.
BIOORGANIC CHEMISTRY
(2021)
Article
Neurosciences
Satish Krishnamurthy, Stephanie Zyck, Jie Li, David Lehmann
Summary: This article discusses the mechanisms of hydrocephalus associated with long term spaceflight (HALS) and suggests several factors that may contribute to its development. These factors include microgravity, hypercapnia, venous hypertension, medications, and dietary substances, which may increase protein load in the ventricles and impair transport out of the ventricles, leading to HALS.
Article
Agronomy
Tan Dai, Zhiwen Wang, Xingkai Cheng, Huige Gao, Li Liang, Pengfei Liu, Xili Liu
Summary: Both fungicide efflux and detoxification metabolism are involved in the resistance mechanisms of Phytophthora capsici to SYP-14288.
PEST MANAGEMENT SCIENCE
(2022)
Article
Behavioral Sciences
Andrea Veronica Enrique, Mauricio Emiliano Di Ianni, Sofia Goicoechea, Alberto Lazarowski, Maria Guadalupe Valle-Dorado, Juan Jose Lopez Costa, Luisa Rocha, Elena Girardi, Alan Talevi
Summary: Despite the approval of many new antiepileptic drugs, seizure control globally has not improved significantly. The article discusses the transporter hypothesis and neuroinflammation causing P-glycoprotein upregulation as potential reasons for drug-resistant epilepsy. Through ligand-based screening, compounds with dual anticonvulsant and anti-inflammatory effects were identified, with sebacic acid showing promising results.
EPILEPSY & BEHAVIOR
(2021)
Review
Pharmacology & Pharmacy
Sachin Rathod, Pratap Bahadur, Sanjay Tiwari
Summary: alpha-Tocopheryl polyethylene glycol succinate (TPGS) is a safe excipient that can enhance drug solubility and dispersion. Its aggregation behavior can be modulated by other amphiphiles and organic additives, allowing for the development of various drug formulations. TPGS improves drug bioavailability by enhancing permeation and reducing levels of P-glycoproteins.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Rasmus Blaaholm Nielsen, Rene Holm, Ils Pijpers, Jan Snoeys, Ulla Gro Nielsen, Carsten Uhd Nielsen
Summary: This study aimed to investigate the potential of the combination of the P-gp inhibitor zosuquidar and the nonionic surfactant polysorbate 20 in potentiating P-gp-mediated efflux inhibition. Cell-based experiments and animal experiments revealed that the combination of these two substances can enhance P-gp inhibition in vitro. However, in vivo experiments showed that coadministration of both substances leads to a decrease in oral etoposide bioavailability.
Review
Medicine, Research & Experimental
Chunyan Duan, Mingjia Yu, Jiyuan Xu, Bo-Yi Li, Ying Zhao, Ranjith Kumar Kankala
Summary: Multi-drug resistance (MDR) in cancer cells is a significant obstacle in effective drug therapy, resulting from over expression of ATP-binding cassette (ABC) transporter proteins. Various strategies have been proposed to overcome MDR, including co-delivery of drugs with MDR inhibitors, increased dosage and frequency of administration, and combination therapies. This review discusses the reasons and mechanisms behind MDR, such as drug efflux mediated by permeability glycoprotein (P-gp) and other pumps, reduced drug uptake, altered DNA repair, and drug targets. It also explores nanomaterials-based supramolecular designs and physical approaches for MDR treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Parijat Pandey, Hitesh Chopra, Deepak Kaushik, Ravinder Verma, Deepika Purohit, Jatin Parashar, Vineet Mittal, Md. Habibur Rahman, Saurabh Bhatia, Pradeep Kumar, Tanima Bhattacharya, Priti Tagde, Ahmed Al-Harrasi
Summary: Cancer remains a leading cause of death worldwide, and while there are treatment options available, their adverse effects often outweigh their therapeutic benefits. Nanotechnology shows promise in addressing these issues, but further development is needed. Stimuli-responsive nanomedicine, dendrimers, micelles, and lipid-based nano-formulations have been explored for their efficacy in cancer treatment. This review paper highlights significant patents granted/applied globally that utilize nanotechnology for cancer treatment, with focus on enhancing the ADME profile of therapeutic molecules.
RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY
(2023)
Review
Biochemistry & Molecular Biology
Sunaina Indermun, Pradeep Kumar, Mershen Govender, Yahya E. E. Choonara
Summary: Tyrosine kinase inhibitors (TKIs) are effective drug molecules for treating various cancers. Nanomedicinal interventions and approaches can enhance the efficacy of TKIs by providing carrying capacities and potentially targeting tumor-specific environments and cellular compartments. Different nanosystems have been developed for TKI delivery in cancer treatment, with each having their own preparation methods and physicochemical properties. This review discusses the applicability of nano-interventions for combination therapies, dose reduction, and improved treatment outcomes, highlighting the efficacy of developed nanosystems against different cancer cell lines and models.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Polymer Science
Sindy P. Ndlovu, Thierry Y. Fonkui, Pradeep Kumar, Yahya E. Choonara, Derek T. Ndinteh, Blessing A. Aderibigbe
Summary: A major challenge in treating burn wounds is bacteria invasion which prolongs the wound healing process. To address the issue of skin tears caused by removal of wound dressings, researchers designed dissolvable wound dressings that can be easily removed without causing tears, while also exhibiting desirable antibacterial activity and absorption capability.
Article
Polymer Science
Mershen Govender, Thankhoe A. Rants'o, Yahya E. Choonara
Summary: A micro-in-macro gastroretentive and gastrofloatable drug delivery system (MGDDS) loaded with ciprofloxacin was developed to overcome the limitations of narrow-absorption window (NAW) drug delivery. The system, consisting of microparticles loaded in a gastrofloatable macroparticle, successfully modified the release of ciprofloxacin and increased drug absorption. This study demonstrates the potential of the MGDDS in delivering other NAW drugs.
Article
Polymer Science
Thashree Marimuthu, Zainul Sidat, Pradeep Kumar, Yahya E. Choonara
Summary: This study compares the effectiveness of an ionic liquid (IL) agent, [HMIM]Cl, as a plasticizer in comparison to current industry standards. The results show that [HMIM]Cl is a more effective plasticizer than the tested standards, even at concentrations as low as 20-30% w/w. Additionally, the combination of [HMIM]Cl with a standard plasticizer demonstrates remarkable plasticizing capability and long-term stability.
Review
Pharmacology & Pharmacy
Maan Singh, Harsh Barua, Vaskuri G. S. Sainaga Jyothi, Madhukiran R. Dhondale, Amritha G. Nambiar, Ashish K. Agrawal, Pradeep Kumar, Nalini R. Shastri, Dinesh Kumar
Summary: Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability can be effectively improved through the cocrystallization process with suitable coformers. Carboxylic acid-based coformers, such as fumaric acid, oxalic acid, succinic acid, and citric acid, are commonly used and have proven to be effective in API cocrystal formation. This review summarizes the role of coformers in enhancing the physicochemical and pharmaceutical properties of APIs and discusses the patentability and regulatory issues related to pharmaceutical cocrystals.
Review
Pharmacology & Pharmacy
Kruti Naik, Lisa C. Du Toit, Naseer Ally, Yahya E. Choonara
Summary: The vitreous humour is a gel-like structure that forms the majority of the eye and has important functions. Current vitreous substitutes have limitations and there is ongoing research on natural, modified, and synthetic polymers as substitutes. This review discusses the advantages and disadvantages of current substitutes and focuses on polysaccharide and synthetic polymer-based substitutes, as well as presenting innovative approaches and future perspectives in this field.
Article
Biochemistry & Molecular Biology
Divesha Essa, Pierre P. D. Kondiah, Pradeep Kumar, Yahya E. E. Choonara
Summary: In this study, quercetin-loaded PLGA nanoparticles were prepared and optimized. It was found that coating with chitosan increased the cellular uptake of the nanoparticles and folic acid targeting provided selective toxicity and enhanced uptake in LnCap prostate cancer cells. The targeted nano-system exhibited sustained, pH-dependent quercetin release, higher cytotoxicity, and cellular uptake in LnCap cells compared to non-targeted nano-system.
Review
Biochemistry & Molecular Biology
Divya Thirumal, Rakesh K. Sindhu, Shuchi Goyal, Aayush Sehgal, Ashok Kumar, Marianesan Arockia Babu, Pradeep Kumar
Summary: Psoriasis is an inflammatory skin condition that causes various diseases and significantly affects patients' quality of life. It not only impairs the skin but also affects other parts of the body. Many variables can directly or indirectly impact the etiology of psoriasis. Psoriasis affects approximately 2% of the world's population, and significant progress has been made in understanding and treating alternative forms of psoriasis.
Review
Plant Sciences
Arvind Sharma, Harapriya Mohapatra, Kanika Arora, Ritchu Babbar, Rashmi Arora, Poonam Arora, Pradeep Kumar, Evren Algin Yapar, Kailash Rani, Maninder Meenu, Marianesan Arockia Babu, Maninderjit Kaur, Rakesh K. Sindhu
Summary: This review provides insights into plant and herbal formulations for preventing hair loss and stimulating new hair growth, focusing on the molecular mechanisms of hair growth and loss, hair growth-promoting phytoconstituents, and the application of nanoarchitectonic technologies.
Article
Biochemistry & Molecular Biology
Shazia Mansoor, Samson A. Adeyemi, Pierre P. D. Kondiah, Yahya E. Choonara
Summary: This study developed a thermoresponsive hydrogel by co-forming Pluronic F-127 and structurally robust chitosan via EDC/NHS coupling. The hydrogel demonstrated good injectability and controlled release of insulin, making it a promising alternative for closed-loop insulin delivery systems.
Review
Chemistry, Multidisciplinary
Bwalya A. Witika, Yahya E. Choonara, Patrick H. Demana
Summary: The formulation of poorly soluble drugs is a major challenge in drug design, development, and delivery. Conventional formulation strategies often fail to address this issue, leading to the abandonment of potential drug candidates. Nanocrystals and co-crystals offer promising solutions, combining the advantages of crystal engineering and nanoscience. Nano co-crystals can improve drug bioavailability and reduce side effects, serving as carrier-free drug delivery systems. This article reviews the strengths, weaknesses, opportunities, and threats of nano co-crystals, providing insights into their key aspects.
