Renal-Selective Delivery and Angiotensin-Converting Enzyme Inhibition by Subcutaneously Administered Captopril-Lysozyme

Prakash, Jai; Loenen-Weemaes, A. M. Van; Haas, M; Proost, Johannes H.; Meijer, Dirk K. F.; Moolenaar, Frits; Poelstra, Klaas; Kok, Robbert J.

doi:10.1124/dmd.104.002808

Cited by 19 publications

(11 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…administration (Prakash et al, 2005b). We used this knowl- jpet.aspetjournals.org edge to design a protocol for the pharmacokinetic studies with SB-ULS-LZM that allowed optimal estimation of the pharmacokinetic parameters.…”

Section: Pharmacokinetics Of Sb-uls-lzm Conjugatementioning

confidence: 99%

Intracellular Delivery of the p38 Mitogen-Activated Protein Kinase Inhibitor SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in Renal Tubular Cells: A Novel Strategy to Treat Renal Fibrosis

Prakash¹,

Sandovici²,

Saluja³

et al. 2006

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

During renal injury, activation of p38 mitogen-activated protein kinase (MAPK) in proximal tubular cells plays an important role in the inflammatory events that eventually lead to renal fibrosis. We hypothesized that local inhibition of p38 within these cells may be an interesting approach for the treatment of renal fibrosis. To effectuate this, we developed a renal-specific conjugate of the p38 inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] and the carrier lysozyme. First, we demonstrated that SB202190 inhibited the expression of albumin-induced proinflammatory (monocyte chemoattractant protein-1) and transforming growth factor (TGF)-␤1-induced profibrotic (procollagen-I␣1) genes over 50% in renal tubular cells (normal rat kidney-

show abstract

Section: Pharmacokinetics Of Sb-uls-lzm Conjugatementioning

confidence: 99%

Intracellular Delivery of the p38 Mitogen-Activated Protein Kinase Inhibitor SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in Renal Tubular Cells: A Novel Strategy to Treat Renal Fibrosis

Prakash¹,

Sandovici²,

Saluja³

et al. 2006

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…A reduction in the proximal tubular reuptake of a 14 kDa lysozyme-based renal targeting drug carrier after being administered to an adriamycin model of advanced renal disease in rats was also reported. 49 This further supports the importance of having a functional renal reuptake mechanism when a tubular reuptake-based renal targeting drug carrier is used.…”

Section: Discussionmentioning

confidence: 65%

Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

Chai¹,

Kiew²,

Chin³

et al. 2017

IJN

View full text Add to dashboard Cite

“…The levels of total captopril that were measured in the current study are in good agreement with those obtained from previous pharmacokinetic data after a single s.c. injection. 13 Furthermore, our data demonstrate a substantial decrease in the percentage of free captopril in plasma by coupling of the drug to lysozyme. Previously, it had been observed that the conjugate does not inhibit plasma ACE.…”

Section: Discussionmentioning

confidence: 84%

“…be renoselective to an extent that anti-proteinuric effects were observed, without any effect on blood pressure in nephrotic rats on a high sodium diet. In a previous study employing single injections in healthy animals, subcutaneous (s.c.) injection was shown to be an adequate route of administration to deliver the captopril-lysozyme conjugate, 13 as the conjugate was almost completely absorbed from the injection site, remained stable and displayed a prolonged residence time in the kidneys. Furthermore, the single s.c. dose of captoprillysozyme conjugate produced a moderate but sustained inhibition of renal ACE during the 24-hour observation period, with no effects on plasma ACE.…”

Section: Discussionmentioning

confidence: 99%

Renal targeting of captopril using captopril-lysozyme conjugate enhances its antiproteinuric effect in adriamycin-induced nephrosis

Windt

Prakash

Kok

et al. 2004

J Renin Angiotensin Aldosterone Syst

Self Cite

View full text Add to dashboard Cite

Introduction High-sodium intake blunts the renoprotective efficacy of angiotensin-converting enzyme (ACE) inhibitors. We investigated whether targeting the drug to the kidneys may attenuate the inferior response to ACE inhibitor (ACE-I) under high-sodium conditions. The ACE-I, captopril, was coupled to the low molecular weight protein (LMWP) lysozyme, yielding captopril-lysozyme conjugates that accumulate specifically in the proximal tubular cells of the kidneys.We compared the antiproteinuric efficacy of captopril to that of the captopril-lysozyme conjugate in adriamycin-induced proteinuric rats fed with a high-sodium diet. Materials and methods Rats with adriamycin (single injection 2 mg/kg)-induced proteinuria were put on a high-sodium diet (HS; 3% NaCl). When stable proteinuria developed at 5.5 weeks, animals were assigned to the following subcutaneous treatments: (1) vehicle (n=7); (2) lysozyme (equivalent to the amount in conjugate) (n=7); (3) captopril (5 mg/kg/24 hours) (n=8); (4) captopril-lysozyme conjugate (captopril content equivalent to 1mg captopril/kg/24 hours) (n=7). Blood pressure and proteinuria were monitored. After 10 days of treatment the rats were sacrificed and kidneys and plasma were removed. Results Results are given as mean + S.E.M. After injection with adriamycin at t=0, stable proteinuria developed, amounting to 547+79 mg/24 hours at week 5.5. Subsequently, after seven and nine days of treatment, no reduction of proteinuria was observed in the captopril-treated group. In contrast, a significant reduction in proteinuria, amounting to 35+4% (day seven) and 25+2% (day nine), was observed in the captopril-lysozyme conjugate group (p<0.05 compared with the captopril group). In contrast, blood pressure was reduced in the captopril-treated group by 13.9+2.9 mmHg, while in the captopril-lysozyme treated group, an increase of 7.9+3.3 mmHg was found. Renal ACE activity was lowered by 30% in the captopril, as well as in the captopril-lysozyme conjugate treated group, compared with control. Furthermore, the ratio of kidney: plasma levels of captopril almost doubled as a consequence of coupling to lysozyme. Conclusion In proteinuric rats fed with a high-sodium diet, captopril induced a reduction in blood pressure without an effect on proteinuria. In contrast, renal targeting of a five times lower dose of the ACE-I with the captopril-lysozyme conjugate reduced proteinuria without reducing blood pressure. Therefore, renal targeting of ACE-I may be a promising strategy to optimise the therapeutic response of ACE-I.

show abstract

Renal-Selective Delivery and Angiotensin-Converting Enzyme Inhibition by Subcutaneously Administered Captopril-Lysozyme

Cited by 19 publications

References 18 publications

Intracellular Delivery of the p38 Mitogen-Activated Protein Kinase Inhibitor SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in Renal Tubular Cells: A Novel Strategy to Treat Renal Fibrosis

Intracellular Delivery of the p38 Mitogen-Activated Protein Kinase Inhibitor SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in Renal Tubular Cells: A Novel Strategy to Treat Renal Fibrosis

Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

Renal targeting of captopril using captopril-lysozyme conjugate enhances its antiproteinuric effect in adriamycin-induced nephrosis

Contact Info

Product

Resources

About