Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study

El-Salamouni, Noha S.; Gowayed, Mennatallah A.; Seiffein, Nevine L.; Abd-el-Moneim, Rehab; Kamel, Maher A.; Labib, Gihan S

doi:10.1016/j.ijpharm.2020.120091

Cited by 36 publications

(14 citation statements)

References 61 publications

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“…Another unconventional SLNs hydrogel was designed by loading Valsartan as an angiotensin II blocker to exploit its demonstrated efficacy on diabetic ulcers. The formulation with high entrapment efficacy and an extended release manifested a significant diabetic foot wound shrinking including a notable reduction in COX-2, MMP, and NF-κB and a significant disruption to filming formation of both gram-positive and negative bacteria [ 107 ]. Opioids induce keratinocyte migration caused by increased nitric oxide production.…”

Section: Mechanism Of Lipid-based Drug Delivery Systemsmentioning

confidence: 99%

Combinational System of Lipid-Based Nanocarriers and Biodegradable Polymers for Wound Healing: An Updated Review

Far

Naimi-Jamal

Sedaghat

et al. 2023

JFB

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Skin wounds have imposed serious socioeconomic burdens on healthcare providers and patients. There are just more than 25,000 burn injury-related deaths reported each year. Conventional treatments do not often allow the re-establishment of the function of affected regions and structures, resulting in dehydration and wound infections. Many nanocarriers, such as lipid-based systems or biobased and biodegradable polymers and their associated platforms, are favorable in wound healing due to their ability to promote cell adhesion and migration, thus improving wound healing and reducing scarring. Hence, many researchers have focused on developing new wound dressings based on such compounds with desirable effects. However, when applied in wound healing, some problems occur, such as the high cost of public health, novel treatments emphasizing reduced healthcare costs, and increasing quality of treatment outcomes. The integrated hybrid systems of lipid-based nanocarriers (LNCs) and polymer-based systems can be promising as the solution for the above problems in the wound healing process. Furthermore, novel drug delivery systems showed more effective release of therapeutic agents, suitable mimicking of the physiological environment, and improvement in the function of the single system. This review highlights recent advances in lipid-based systems and the role of lipid-based carriers and biodegradable polymers in wound healing.

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Section: Mechanism Of Lipid-based Drug Delivery Systemsmentioning

confidence: 99%

Combinational System of Lipid-Based Nanocarriers and Biodegradable Polymers for Wound Healing: An Updated Review

Far

Naimi-Jamal

Sedaghat

et al. 2023

JFB

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“…Chronic diabetic wounds are a serious complication of diabetes, which often leads to high costs of treatment and high rates of amputation [ 1 , 2 ]. Many studies have attempted to explore the causes of chronic diabetic wound non-healing due to the difference in the physiological environment of acute and chronic wounds [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

Zhou

Duan

Zhao

et al. 2022

Bioactive Materials

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“…Nitric oxide (NO) generation, which has a vital role in microvascular homeostasis, angiogenesis, epidermal migration, formation of granulation tissue, and collagen deposition in the wound, is also impaired in diabetes (3). Some existing drugs have been investigated in drug repurposing efforts, such as statins, phenytoin, metformin, propranolol, valsartan, as well as DPP-4 inhibitors, but have limited or no efficacy for wound healing (4)(5)(6)(7)(8)(9). Topical phenytoin was shown to reduce the time for granulation tissue in ulcers as well as promote a reduction in the size of ulcers (4).…”

Section: Introductionmentioning

confidence: 99%

“…Some existing drugs have been investigated in drug repurposing efforts, such as statins, phenytoin, metformin, propranolol, valsartan, as well as DPP-4 inhibitors, but have limited or no efficacy for wound healing ( 4 – 9 ). Topical phenytoin was shown to reduce the time for granulation tissue in ulcers as well as promote a reduction in the size of ulcers ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…In diabetic mice, DPP-4 inhibitors have been shown to promote the migration of keratinocytes ( 8 ). Treatment with a nano-formulation of valsartan showed enhanced healing in diabetic rats through the COX-2, NF-κB, nitric oxide, TGF-β, and VEGF pathways ( 9 ). The complex multifactorial pathways involved in diabetic wound healing with limited pharmacological therapies suggest the need for the development of newer treatment modalities.…”

Section: Introductionmentioning

confidence: 99%

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Novel topical esmolol hydrochloride improves wound healing in diabetes by inhibiting aldose reductase, generation of advanced glycation end products, and facilitating the migration of fibroblasts

Kulkarni

Deshpande²,

Rastogi³

2022

Front. Endocrinol.

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Aims/ObjectivesWound healing in people with diabetes is delayed secondary to impaired nitric oxide generation, advanced glycation end products (AGE), and poor migration of epithelial cells. We developed a novel topical esmolol hydrochloride (Galnobax) and assessed its efficacy for wound healing in streptozocin-induced diabetic hairless rat.MethodsAll experiments were performed at an animal laboratory and tertiary-care research facility. Ex vivo aldose reductase inhibition was assessed from enzymes obtained from a bacterial culture (spectrophotometer), sorbitol content in homogenized red blood cells, and AGE in glucose and bovine serum by fluorometry following the addition of esmolol in varying concentrations. A scratch assay of human fibroblasts, endothelial cells, and keratinocytes was assessed under a high-glucose environment and after esmolol by phase-contrast microscopy. The efficacy evaluation of the topical application of Galnobax (14 and 20%) or vehicle was conducted in streptozotocin-induced diabetic hairless rats, and endogenous nitrite and hydroxyproline from homogenized wound tissue were measured along with pharmacokinetic and dermal toxicity in Hanford miniature swine.ResultsEsmolol inhibited the formation of sorbitol by 59% in erythrocytes in comparison to glucose-induced sorbitol levels. AGE generation in bovine serum albumin was reduced at 1 mM esmolol concentrations (2.6 ± 1.7) compared with control (p < 0.05) and similar to that of diclofenac (2.5 ± 1.3). Esmolol at 1 and 10 µM enhanced the migration of fibroblasts, epithelial cells, and keratinocytes compared with control. The nitric oxide levels (day 7) were 44 and 112% higher with Galnobax (14%) than those of the diabetic group (p < 0.05) and the vehicle control group (p < 0.05), respectively. The days 7 and 14 hydroxyproline in the wound was higher by 22 and 44% following Galnobax (14%) compared with the diabetic and vehicle control groups. The wound area exhibited better reduction with Galnobax at 14% up to day 10 follow-up compared with the controls. The pharmacokinetic and dermal toxicity in miniature swine suggested no significant adverse event with Galnobax.ConclusionsTopical esmolol hydrochloride is a novel, safe, and effective treatment modality that acts through pleotropic mechanisms to hasten wound healing in diabetes.

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Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study

Cited by 36 publications

References 61 publications

Combinational System of Lipid-Based Nanocarriers and Biodegradable Polymers for Wound Healing: An Updated Review

Combinational System of Lipid-Based Nanocarriers and Biodegradable Polymers for Wound Healing: An Updated Review

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

Novel topical esmolol hydrochloride improves wound healing in diabetes by inhibiting aldose reductase, generation of advanced glycation end products, and facilitating the migration of fibroblasts

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