Implementing losartan potassium-laden pegylated nanocubic vesicles as a novel nanoplatform to alleviate cisplatin-induced nephrotoxicity via blocking apoptosis and activating the wnt/β-catenin/TCF-4 pathway

Losartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking apoptosis and activating wnt/β-catenin pathway. Utilizing a thin-film hydration methodology established on 42 full factorial design to produce LP lo...

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Published inLife sciences (1973) Vol. 354; p. 122955
Main Authors Salem, Heba F., Nafady, Mohamed M., Khallaf, Rasha A., Abdel-Sattar, Asmaa Ramadan, Abdel-Sattar, Hend Hassan, Eissa, Essam M.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Inc 01.10.2024
Subjects
Acute Kidney Injury - chemically induced
Acute Kidney Injury - drug therapy
Acute Kidney Injury - metabolism
Acute Kidney Injury - pathology
Acute Kidney Injury - prevention & control
Animals
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
beta Catenin - metabolism
Cisplatin
Drug Liberation
Kidney - drug effects
Kidney - metabolism
Kidney - pathology
Kidney injury
Losartan - pharmacology
Losartan potassium
Male
Nanoparticles - chemistry
Polyethylene Glycols - chemistry
Rats
Rats, Wistar
TCF-4
Transcription Factor 4 - metabolism
Wnt
Wnt Signaling Pathway - drug effects
TCF-4
Losartan potassium
Wnt
Kidney injury
Cisplatin
Apoptosis
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Abstract Losartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking apoptosis and activating wnt/β-catenin pathway. Utilizing a thin-film hydration methodology established on 42 full factorial design to produce LP loaded nanocubic formulations (LP-NCVs) which composed mainly from L-α-phosphatidylcholine and poloxamer. The optimization process was designed to select the formulation with maximum entrapment efficiency (EE %), maximum in-vitro drug release (Q8h), and minimum vesicle size (VS). The optimum formulation was then pegylated to obtain LP-NCVs-PEG formulation that shields NCVs from the harsh ecosystem of the stomach, improves their oral drug delivery performance and targets the proximal renal tubules with no systemic toxicity. Male albino rats were injected with Cisplatin (6 mg/kg, i.p.) alone or with LP-formulations (5 mg/kg/day). Kidney injury markers, inflammatory markers, apoptotic markers. Besides renal tissue expression of Wnt, β-Catenin, GSK-3β, renal RNA gene expression of TCF-4, LEF-1 and histopathology were also analyzed to display pharmacological study. The pharmacokinetics studies demonstrated that LP-NCVs-PEG boosted LP bioavailability approximately 3.61 times compared to LP oral solution. Besides LP-NCVs-PEG may have an intriguing kidney-targeted nanoplatform for acute renal injury via decreased renal toxicity markers, renal expression of LEF-1, GSK3-β, caspase, TNF-α, NF-κB and TUNEL expression. Alternatively, increased renal tissue level of Bcl-2, wnt, β-catenin and TCF-4. LP-NCVs-PEG improved LP pharmacokinetics targeting the kidney and improved injury by activating wnt/β-catenin/TCF-4 pathway, blocking apoptosis, inflammation and renal toxicity markers suggesting it might be successful nephroprotective adjuvant therapy. [Display omitted]
AbstractList Losartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking apoptosis and activating wnt/β-catenin pathway.AIMSLosartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking apoptosis and activating wnt/β-catenin pathway.Utilizing a thin-film hydration methodology established on 42 full factorial design to produce LP loaded nanocubic formulations (LP-NCVs) which composed mainly from L-α-phosphatidylcholine and poloxamer. The optimization process was designed to select the formulation with maximum entrapment efficiency (EE %), maximum in-vitro drug release (Q8h), and minimum vesicle size (VS). The optimum formulation was then pegylated to obtain LP-NCVs-PEG formulation that shields NCVs from the harsh ecosystem of the stomach, improves their oral drug delivery performance and targets the proximal renal tubules with no systemic toxicity. Male albino rats were injected with Cisplatin (6 mg/kg, i.p.) alone or with LP-formulations (5 mg/kg/day). Kidney injury markers, inflammatory markers, apoptotic markers. Besides renal tissue expression of Wnt, β-Catenin, GSK-3β, renal RNA gene expression of TCF-4, LEF-1 and histopathology were also analyzed to display pharmacological study.MAIN METHODSUtilizing a thin-film hydration methodology established on 42 full factorial design to produce LP loaded nanocubic formulations (LP-NCVs) which composed mainly from L-α-phosphatidylcholine and poloxamer. The optimization process was designed to select the formulation with maximum entrapment efficiency (EE %), maximum in-vitro drug release (Q8h), and minimum vesicle size (VS). The optimum formulation was then pegylated to obtain LP-NCVs-PEG formulation that shields NCVs from the harsh ecosystem of the stomach, improves their oral drug delivery performance and targets the proximal renal tubules with no systemic toxicity. Male albino rats were injected with Cisplatin (6 mg/kg, i.p.) alone or with LP-formulations (5 mg/kg/day). Kidney injury markers, inflammatory markers, apoptotic markers. Besides renal tissue expression of Wnt, β-Catenin, GSK-3β, renal RNA gene expression of TCF-4, LEF-1 and histopathology were also analyzed to display pharmacological study.The pharmacokinetics studies demonstrated that LP-NCVs-PEG boosted LP bioavailability approximately 3.61 times compared to LP oral solution. Besides LP-NCVs-PEG may have an intriguing kidney-targeted nanoplatform for acute renal injury via decreased renal toxicity markers, renal expression of LEF-1, GSK3-β, caspase, TNF-α, NF-κB and TUNEL expression. Alternatively, increased renal tissue level of Bcl-2, wnt, β-catenin and TCF-4.KEY FINDINGSThe pharmacokinetics studies demonstrated that LP-NCVs-PEG boosted LP bioavailability approximately 3.61 times compared to LP oral solution. Besides LP-NCVs-PEG may have an intriguing kidney-targeted nanoplatform for acute renal injury via decreased renal toxicity markers, renal expression of LEF-1, GSK3-β, caspase, TNF-α, NF-κB and TUNEL expression. Alternatively, increased renal tissue level of Bcl-2, wnt, β-catenin and TCF-4.LP-NCVs-PEG improved LP pharmacokinetics targeting the kidney and improved injury by activating wnt/β-catenin/TCF-4 pathway, blocking apoptosis, inflammation and renal toxicity markers suggesting it might be successful nephroprotective adjuvant therapy.SIGNIFICANCELP-NCVs-PEG improved LP pharmacokinetics targeting the kidney and improved injury by activating wnt/β-catenin/TCF-4 pathway, blocking apoptosis, inflammation and renal toxicity markers suggesting it might be successful nephroprotective adjuvant therapy.
Losartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking apoptosis and activating wnt/β-catenin pathway. Utilizing a thin-film hydration methodology established on 42 full factorial design to produce LP loaded nanocubic formulations (LP-NCVs) which composed mainly from L-α-phosphatidylcholine and poloxamer. The optimization process was designed to select the formulation with maximum entrapment efficiency (EE %), maximum in-vitro drug release (Q8h), and minimum vesicle size (VS). The optimum formulation was then pegylated to obtain LP-NCVs-PEG formulation that shields NCVs from the harsh ecosystem of the stomach, improves their oral drug delivery performance and targets the proximal renal tubules with no systemic toxicity. Male albino rats were injected with Cisplatin (6 mg/kg, i.p.) alone or with LP-formulations (5 mg/kg/day). Kidney injury markers, inflammatory markers, apoptotic markers. Besides renal tissue expression of Wnt, β-Catenin, GSK-3β, renal RNA gene expression of TCF-4, LEF-1 and histopathology were also analyzed to display pharmacological study. The pharmacokinetics studies demonstrated that LP-NCVs-PEG boosted LP bioavailability approximately 3.61 times compared to LP oral solution. Besides LP-NCVs-PEG may have an intriguing kidney-targeted nanoplatform for acute renal injury via decreased renal toxicity markers, renal expression of LEF-1, GSK3-β, caspase, TNF-α, NF-κB and TUNEL expression. Alternatively, increased renal tissue level of Bcl-2, wnt, β-catenin and TCF-4. LP-NCVs-PEG improved LP pharmacokinetics targeting the kidney and improved injury by activating wnt/β-catenin/TCF-4 pathway, blocking apoptosis, inflammation and renal toxicity markers suggesting it might be successful nephroprotective adjuvant therapy. [Display omitted]
Losartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking apoptosis and activating wnt/β-catenin pathway. Utilizing a thin-film hydration methodology established on 4 full factorial design to produce LP loaded nanocubic formulations (LP-NCVs) which composed mainly from L-α-phosphatidylcholine and poloxamer. The optimization process was designed to select the formulation with maximum entrapment efficiency (EE %), maximum in-vitro drug release (Q ), and minimum vesicle size (VS). The optimum formulation was then pegylated to obtain LP-NCVs-PEG formulation that shields NCVs from the harsh ecosystem of the stomach, improves their oral drug delivery performance and targets the proximal renal tubules with no systemic toxicity. Male albino rats were injected with Cisplatin (6 mg/kg, i.p.) alone or with LP-formulations (5 mg/kg/day). Kidney injury markers, inflammatory markers, apoptotic markers. Besides renal tissue expression of Wnt, β-Catenin, GSK-3β, renal RNA gene expression of TCF-4, LEF-1 and histopathology were also analyzed to display pharmacological study. The pharmacokinetics studies demonstrated that LP-NCVs-PEG boosted LP bioavailability approximately 3.61 times compared to LP oral solution. Besides LP-NCVs-PEG may have an intriguing kidney-targeted nanoplatform for acute renal injury via decreased renal toxicity markers, renal expression of LEF-1, GSK3-β, caspase, TNF-α, NF-κB and TUNEL expression. Alternatively, increased renal tissue level of Bcl-2, wnt, β-catenin and TCF-4. LP-NCVs-PEG improved LP pharmacokinetics targeting the kidney and improved injury by activating wnt/β-catenin/TCF-4 pathway, blocking apoptosis, inflammation and renal toxicity markers suggesting it might be successful nephroprotective adjuvant therapy.
ArticleNumber 122955
Author Khallaf, Rasha A.
Salem, Heba F.
Abdel-Sattar, Asmaa Ramadan
Abdel-Sattar, Hend Hassan
Eissa, Essam M.
Nafady, Mohamed M.
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  surname: Nafady
  fullname: Nafady, Mohamed M.
  email: mohamed.abdelfatah@nub.edu.eg
  organization: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Nahda University Beni-Suef, Egypt
– sequence: 3
  givenname: Rasha A.
  surname: Khallaf
  fullname: Khallaf, Rasha A.
  email: Rasha.mahmoud@pharm.bsu.edu.eg
  organization: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
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  organization: Pharmacology and Toxicology Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt
– sequence: 5
  givenname: Hend Hassan
  surname: Abdel-Sattar
  fullname: Abdel-Sattar, Hend Hassan
  email: hend.abdelsatar@nub.edu.eg
  organization: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Nahda University Beni-Suef, Egypt
– sequence: 6
  givenname: Essam M.
  surname: Eissa
  fullname: Eissa, Essam M.
  email: essam.mohamed@pharm.bsu.edu.eg
  organization: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
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Keywords TCF-4
Losartan potassium
Wnt
Kidney injury
Cisplatin
Apoptosis
Language English
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Snippet Losartan potassium-laden pegylated nanocubic vesicles (LP-NCVs-PEG) have an intriguing kidney-targeted nanoplatform for acute renal injury via blocking...
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StartPage 122955
SubjectTerms Acute Kidney Injury - chemically induced
Acute Kidney Injury - drug therapy
Acute Kidney Injury - metabolism
Acute Kidney Injury - pathology
Acute Kidney Injury - prevention & control
Animals
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
beta Catenin - metabolism
Cisplatin
Drug Liberation
Kidney - drug effects
Kidney - metabolism
Kidney - pathology
Kidney injury
Losartan - pharmacology
Losartan potassium
Male
Nanoparticles - chemistry
Polyethylene Glycols - chemistry
Rats
Rats, Wistar
TCF-4
Transcription Factor 4 - metabolism
Wnt
Wnt Signaling Pathway - drug effects
Title Implementing losartan potassium-laden pegylated nanocubic vesicles as a novel nanoplatform to alleviate cisplatin-induced nephrotoxicity via blocking apoptosis and activating the wnt/β-catenin/TCF-4 pathway
URI https://dx.doi.org/10.1016/j.lfs.2024.122955
https://www.ncbi.nlm.nih.gov/pubmed/39122109
https://www.proquest.com/docview/3091284029
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