{"title":"Recent advances in GPR35 pharmacology; 5-HIAA serotonin metabolite becomes a ligand","authors":"Dong-Soon Im","doi":"10.1007/s12272-023-01449-y","DOIUrl":"10.1007/s12272-023-01449-y","url":null,"abstract":"<div><p>GPR35, an orphan receptor, has been waiting for its ligand since its cloning in 1998. Many endogenous and exogenous molecules have been suggested to act as agonists of GPR35 including kynurenic acid, zaprinast, lysophosphatidic acid, and CXCL17. However, complex and controversial responses to ligands among species have become a huge hurdle in the development of therapeutics in addition to the orphan state. Recently, a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), is reported to be a high potency ligand for GPR35 by investigating the increased expression of GPR35 in neutrophils. In addition, a transgenic knock-in mouse line is developed, in which GPR35 was replaced with a human ortholog, making it possible not only to overcome the different selectivity of agonists among species but also to conduct therapeutic experiments on human GPR35 in mouse models. In the present article, I review the recent advances and prospective therapeutic directions in GPR35 research. Especially, I’d like to draw attention of readers to the finding of 5-HIAA as a ligand of GPR35 and lead to apply the 5-HIAA and human GPR35 knock-in mice to their research fields in a variety of pathophysiological conditions.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"550 - 563"},"PeriodicalIF":6.7,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy subjects","authors":"Pureum Kang, Chang-Keun Cho, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Chang-Ik Choi, Jung-Woo Bae","doi":"10.1007/s12272-023-01448-z","DOIUrl":"10.1007/s12272-023-01448-z","url":null,"abstract":"<div><p>Gliclazide metabolism is mediated by genetically polymorphic CYP2C9 and CYP2C19 enzymes. We investigated the effects of <i>CYP2C9</i> and <i>CYP2C19</i> genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide. Twenty-seven Korean healthy volunteers were administered a single oral dose of gliclazide 80 mg. The plasma concentration of gliclazide was quantified for the pharmacokinetic analysis and plasma concentrations of glucose and insulin were measured as pharmacodynamic parameters. The pharmacokinetics of gliclazide showed a significant difference according to the number of defective alleles of combined <i>CYP2C9</i> and <i>CYP2C19</i>. The two defective alleles group (group 3) and one defective allele group (group 2) showed 2.34- and 1.46-fold higher AUC<sub>0–∞</sub> (<i>P</i> < 0.001), and 57.1 and 32.3% lower CL/F (<i>P</i> < 0.001), compared to those of the no defective allele group (group 1), respectively. The <i>CYP2C9IM–</i><i>CYP2C19IM</i> group had AUC<sub>0–∞</sub> increase of 1.49-fold (<i>P</i> < 0.05) and CL/F decrease by 29.9% (<i>P</i> < 0.01), compared with the <i>CYP2C9 Normal Metabolizer</i> (<i>CYP2C9NM</i>)–<i>CYP2C19IM</i> group. The <i>CYP2C9NM–CYP2C19PM</i> group and <i>CYP2C9NM–CYP2C19IM</i> group showed 2.41- and 1.51-fold higher AUC<sub>0–∞</sub> (<i>P</i> < 0.001), and 59.6 and 35.4% lower CL/F (<i>P</i> < 0.001), compared to those of the <i>CYP2C9NM–CYP2C19NM</i> group, respectively. The results represented that <i>CYP2C9</i> and <i>CYP2C19</i> genetic polymorphisms significantly affected the pharmacokinetics of gliclazide. Although the genetic polymorphism of <i>CYP2C19</i> had a greater effect on the pharmacokinetics of gliclazide, the genetic polymorphism of <i>CYP2C9</i> also had a significant effect. On the other hand, plasma glucose and insulin responses to gliclazide were not significantly affected by the <i>CYP2C9–CYP2C19</i> genotypes, requiring further well-controlled studies with long-term dosing of gliclazide in diabetic patients.\u0000</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 5","pages":"438 - 447"},"PeriodicalIF":6.7,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01448-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9423494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities","authors":"Ritwik Maiti, Bhumika Patel, Nrupesh Patel, Mehul Patel, Alkesh Patel, Nirav Dhanesha","doi":"10.1007/s12272-023-01447-0","DOIUrl":"10.1007/s12272-023-01447-0","url":null,"abstract":"<div><p>Antibody drug conjugates (ADCs) are promising cancer therapeutics with minimal toxicity as compared to small cytotoxic molecules alone and have shown the evidence to overcome resistance against tumor and prevent relapse of cancer. The ADC has a potential to change the paradigm of cancer chemotherapeutic treatment. At present, 13 ADCs have been approved by USFDA for the treatment of various types of solid tumor and haematological malignancies. This review covers the three structural components of an ADC—antibody, linker, and cytotoxic payload—along with their respective structure, chemistry, mechanism of action, and influence on the activity of ADCs. It covers comprehensive insight on structural role of linker towards efficacy, stability & toxicity of ADCs, different types of linkers & various conjugation techniques. A brief overview of various analytical techniques used for the qualitative and quantitative analysis of ADC is summarized. The current challenges of ADCs, such as heterogeneity, bystander effect, protein aggregation, inefficient internalization or poor penetration into tumor cells, narrow therapeutic index, emergence of resistance, etc., are outlined along with recent advances and future opportunities for the development of more promising next-generation ADCs.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 5","pages":"361 - 388"},"PeriodicalIF":6.7,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9772168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hua-Wei Lv, Qiao-Liang Wang, Meng Luo, Meng-Di Zhu, Hui-Min Liang, Wen-Jing Li, Hai Cai, Zhong-Bo Zhou, Hong Wang, Sheng-Qiang Tong, Xing-Nuo Li
{"title":"Phytochemistry and pharmacology of natural prenylated flavonoids","authors":"Hua-Wei Lv, Qiao-Liang Wang, Meng Luo, Meng-Di Zhu, Hui-Min Liang, Wen-Jing Li, Hai Cai, Zhong-Bo Zhou, Hong Wang, Sheng-Qiang Tong, Xing-Nuo Li","doi":"10.1007/s12272-023-01443-4","DOIUrl":"10.1007/s12272-023-01443-4","url":null,"abstract":"<div><p>Prenylated flavonoids are a special kind of flavonoid derivative possessing one or more prenyl groups in the parent nucleus of the flavonoid. The presence of the prenyl side chain enriched the structural diversity of flavonoids and increased their bioactivity and bioavailability. Prenylated flavonoids show a wide range of biological activities, such as anti-cancer, anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, cardioprotective effects, and anti-osteoclastogenic activities. In recent years, many compounds with significant activity have been discovered with the continuous excavation of the medicinal value of prenylated flavonoids, and have attracted the extensive attention of pharmacologists. This review summarizes recent progress on research into natural active prenylated flavonoids to promote new discoveries of their medicinal value.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 4","pages":"207 - 272"},"PeriodicalIF":6.7,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01443-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9348366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdullah Alanzi, Esraa A. Elhawary, Mohamed L. Ashour, Ashaimaa Y. Moussa
{"title":"Aspergillus co-cultures: A recent insight into their secondary metabolites and microbial interactions","authors":"Abdullah Alanzi, Esraa A. Elhawary, Mohamed L. Ashour, Ashaimaa Y. Moussa","doi":"10.1007/s12272-023-01442-5","DOIUrl":"10.1007/s12272-023-01442-5","url":null,"abstract":"<div><p>There is an urgent need for novel antibiotics to combat emerging resistant microbial strains. One of the most pressing resources is <i>Aspergillus</i> microbial cocultures. The genome of <i>Aspergillus</i> species comprises a far larger number of novel gene clusters than previously expected, and novel strategies and approaches are essential to exploit this potential source of new drugs and pharmacological agents. This is the first review consulting recent developments and chemical diversity of <i>Aspergillus</i> cocultures and highlighting its untapped richness. The analyzed data revealed that cocultivation of several <i>Aspergillus</i> species with other microorganisms, including bacteria, plants, and fungi, is a source of novel bioactive natural products. Various vital chemical skeleton leads were newly produced or augmented in <i>Aspergillus</i> cocultures, among which were taxol, cytochalasans, notamides, pentapeptides, silibinin, and allianthrones. The possibility of mycotoxin production or complete elimination in cocultivations was detected, which pave the way for better decontamination strategies. Most cocultures revealed a remarkable improvement in their antimicrobial or cytotoxic behavior due to their produced chemical patterns; for instance, weldone and asperterrin whose antitumor and antibacterial activities, respectively, were superior. Microbial cocultivation elicited the upregulation or production of specific metabolites whose importance and significance are yet to be revealed. With more than 155 compounds isolated from <i>Aspergillus</i> cocultures in the last 10 years, showing overproduction, reduction, or complete suppression under the optimized coculture circumstances, this study filled a gap for medicinal chemists searching for new lead sources or bioactive molecules as anticancer agents or antimicrobials.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 4","pages":"273 - 298"},"PeriodicalIF":6.7,"publicationDate":"2023-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01442-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9343520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metformin mitigates renal dysfunction in obese insulin-resistant rats via activation of the AMPK/PPARα pathway","authors":"Laongdao Thongnak, Nattavadee Pengrattanachot, Sasivimon Promsan, Nichakorn Phengpol, Prempree Sutthasupha, Krit Jaikumkao, Anusorn Lungkaphin","doi":"10.1007/s12272-023-01439-0","DOIUrl":"10.1007/s12272-023-01439-0","url":null,"abstract":"<div><p>Insulin signaling and lipid metabolism are disrupted by long-term consumption of a high-fat diet (HFD). This disruption can lead to insulin resistance, dyslipidemia and subsequently renal dysfunction as a consequence of the inactivation of the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPARα) or AMPK/PPARα pathways. We investigated the impact of metformin on the prevention of renal dysfunction through the modulation of AMPK-regulated PPARα-dependent pathways in insulin-resistant rats induced by a HFD. Male Wistar rats were fed a HFD for 16 weeks to induce insulin resistance. After insulin resistance had been confirmed, metformin (30 mg/kg) or gemfibrozil (50 mg/kg) was given orally for 8 weeks. Evidence of insulin resistance, dyslipidemia, lipid accumulation and kidney injury were observed in HF rats. Impairment of lipid oxidation, energy metabolism and renal organic anion transporter 3 (Oat3) expression and function were demonstrated in HF rats. Metformin can stimulate the AMPK/PPARα pathways and suppress sterol regulatory element-binding transcription factor 1 (SREBP1) and fatty acid synthase (FAS) signaling (SREBP1/FAS) to enable the regulation of lipid metabolism. Renal inflammatory markers and renal fibrosis expression induced by a HFD were more effectively reduced after metformin treatment than after gemfibrozil treatment. Interestingly, renal Oat3 function and expression and kidney injury were improved following metformin and gemfibrozil treatment. Renal cluster of differentiation 36 (CD36) or sodium glucose cotransporter type 2 (SGLT2) expression did not differ after treatment with metformin or gemfibrozil. Metformin and gemfibrozil could reduce the impairment of renal injury in obese conditions induced by a HFD through the AMPK/PPARα-dependent pathway. Interestingly, metformin demonstrated greater efficacy than gemfibrozil in attenuating renal lipotoxicity through the AMPK-regulated SREBP1/FAS signaling pathway.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 5","pages":"408 - 422"},"PeriodicalIF":6.7,"publicationDate":"2023-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01439-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9420079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The function, mechanisms, and clinical applications of metformin: potential drug, unlimited potentials","authors":"Jianhong Liu, Ming Zhang, Dan Deng, Xiao Zhu","doi":"10.1007/s12272-023-01445-2","DOIUrl":"10.1007/s12272-023-01445-2","url":null,"abstract":"<div><p>Metformin has been used clinically for more than 60 years. As time goes by, more and more miraculous effects of metformin beyond the clinic have been discovered and discussed. In addition to the clinically approved hypoglycemic effect, it also has a positive metabolic regulation effect on the human body that cannot be ignored. Such as anti-cancer, anti-aging, brain repair, cardiovascular protection, gastrointestinal regulation, hair growth and inhibition of thyroid nodules, and other nonclinical effects. Metformin affects almost the entire body in the situation taking it over a long period, and the preventive effects of metformin in addition to treating diabetes are also beginning to be recommended in some guidelines. This review is mainly composed of four parts: the development history of metformin, the progress of clinical efficacy, the nonclinical efficacy of metformin, and the consideration and prospect of its application.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 5","pages":"389 - 407"},"PeriodicalIF":6.7,"publicationDate":"2023-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rania M. Salama, Samah S. Abbas, Samar F. Darwish, Al Aliaa Sallam, Noura F. Elmongy, Sara A. El Wakeel
{"title":"Regulation of NOX/p38 MAPK/PPARα pathways and miR-155 expression by boswellic acids reduces hepatic injury in experimentally-induced alcoholic liver disease mouse model: novel mechanistic insight","authors":"Rania M. Salama, Samah S. Abbas, Samar F. Darwish, Al Aliaa Sallam, Noura F. Elmongy, Sara A. El Wakeel","doi":"10.1007/s12272-023-01441-6","DOIUrl":"10.1007/s12272-023-01441-6","url":null,"abstract":"<div><p>Alcoholic liver disease (ALD) refers to hepatic ailments induced by excessive alcohol intake. The pathogenesis of ALD comprises a complex interplay between various mechanistic pathways, among which inflammation and oxidative stress are key players. Boswellic acids (BAs), found in <i>Boswellia serrata</i>, have shown hepatoprotective effects owing to their antioxidant and anti-inflammatory activities, nevertheless, their therapeutic potential against ALD has not been previously investigated. Hence, this study was performed to depict the possible protective effect of BAs and detect their underlying mechanism of action in an experimentally-induced ALD mouse model. Male BALB/c mice were equally categorized into six groups: control, BAs-treated, ALD, and ALD that received BAs at three-dose levels (125, 250, and 500 mg/kg) by oral gavage for 14 days. Results showed that the high dose of BAs had the most protective impact against ALD according to histopathology examination, blood alcohol concentration (BAC), and liver function enzymes. Mechanistic investigations revealed that BAs (500 mg/kg) caused a significant decrease in cytochrome P450 2E1(CYP2E1), nicotine adenine dinucleotide phosphate oxidase (NOX) 1/2/4, p38 mitogen-activated protein kinase (MAPK), and sterol regulatory element-binding protein-1c (SREBP-1c) levels, and the expression of miR-155, yet increased peroxisome proliferator-activated receptor alpha (PPARα) levels. This led to an improvement in lipid profile and reduced hepatic inflammation, oxidative stress, and apoptosis indices. In summary, our study concludes that BAs can protect against ethanol-induced hepatic injury, via modulating NOX/p38 MAPK/PPARα pathways and miR-155 expression.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 4","pages":"323 - 338"},"PeriodicalIF":6.7,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01441-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yujeong Lee, Hee Ra Park, Joo Yeon Lee, Jaehoon Kim, Seonguk Yang, Chany Lee, Kipom Kim, Hyung Sik Kim, Seung-Cheol Chang, Jaewon Lee
{"title":"Low-dose curcumin enhances hippocampal neurogenesis and memory retention in young mice","authors":"Yujeong Lee, Hee Ra Park, Joo Yeon Lee, Jaehoon Kim, Seonguk Yang, Chany Lee, Kipom Kim, Hyung Sik Kim, Seung-Cheol Chang, Jaewon Lee","doi":"10.1007/s12272-023-01440-7","DOIUrl":"10.1007/s12272-023-01440-7","url":null,"abstract":"<div><p>Adult neurogenesis generates new functional neurons from adult neural stem cells in various regions, including the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of hippocampal dentate gyrus (DG). Available evidence shows hippocampal neurogenesis can be negatively or positively regulated by dietary components. In a previous study, we reported that curcumin (diferuloylmethane; a polyphenolic found in curry spice) stimulates the proliferation of embryonic neural stem cells (NSCs) by activating adaptive cellular stress responses. Here, we investigated whether subchronic administration of curcumin (once daily at 0.4, 2, or 10 mg/kg for 14 days) promotes hippocampal neurogenesis and neurocognitive function in young (5-week-old) mice. Oral administration of low-dose curcumin (0.4 mg/kg) increased the proliferation and survival of newly generated cells in hippocampus, but surprisingly, high-dose curcumin (10 mg/kg) did not effectively upregulate the proliferation or survival of newborn cells. Furthermore, hippocampal BDNF levels and phosphorylated CREB activity were elevated in only low-dose curcumin-treated mice. Passive avoidance testing revealed that low-dose curcumin increased cross-over latency times, indicating enhanced memory retention, and an in vitro study showed that low-concentration curcumin increased the proliferative activity of neural progenitor cells (NPCs) by upregulating NF1X levels. Collectively, our findings suggest that low-dose curcumin has neurogenic effects and that it may prevent age and neurodegenerative disease-related cognitive deficits.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 5","pages":"423 - 437"},"PeriodicalIF":6.7,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01440-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9410905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kanchan Shakhakarmi, Jo-Eun Seo, Shrawani Lamichhane, Chhitij Thapa, Sangkil Lee
{"title":"EGF, a veteran of wound healing: highlights on its mode of action, clinical applications with focus on wound treatment, and recent drug delivery strategies","authors":"Kanchan Shakhakarmi, Jo-Eun Seo, Shrawani Lamichhane, Chhitij Thapa, Sangkil Lee","doi":"10.1007/s12272-023-01444-3","DOIUrl":"10.1007/s12272-023-01444-3","url":null,"abstract":"<div><p>Epidermal growth factor (EGF) has been used in wound management and regenerative medicine since the late 1980s. It has been widely utilized for a long time and still is because of its excellent tolerability and efficacy. EGF has many applications in tissue engineering, cancer therapy, lung diseases, gastric ulcers, and wound healing. Nevertheless, its in vivo and during storage stability is a primary concern. This review focuses on the topical use of EGF, especially in chronic wound healing, the emerging use of biomaterials to deliver it, and future research possibilities. To successfully deliver EGF to wounds, a delivery system that is proteolytically resistant and stable over the long term is required. Biomaterials are an area of interest for the development of such systems. These systems may be used in non-healing wounds such as diabetic foot ulcers, pressure ulcers, and burns. In these pathologies, EGF can reduce the risk of amputation of the lower extremities, as it accelerates the wound healing process. Furthermore, appropriate delivery system would also stabilize and control the EGF release profile in a wound. Several in vitro and in vivo studies have already proven the efficacy of such systems in the above-mentioned types of wounds. Moreover, several formulations such as ointments and intralesional injections are already available on the market. However, these products are still problematic in terms of inadequate diffusion of EGF, low bioavailability storage conditions, and shelf-life. This review discusses the nano formulations comprising biomaterials infused with EGF which could be a promising delivery system for chronic wound healing in the future.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 4","pages":"299 - 322"},"PeriodicalIF":6.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9343263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}