R11, a novel cell‐permeable peptide, as an intravesical delivery vehicle

• Published in: BJU international Vol. 108; no. 10; pp. 1666 - 1671
• Main Authors: Hsieh, Jer‐Tsong, Zhou, Jian, Gore, Crystal, Zimmern, Philippe
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2011; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Administration, Intravesical; Animals; Biological and medical sciences; Biological Availability; Bladder; cell‐permeable peptide; Drug Carriers - administration & dosage; Drug Carriers - pharmacokinetics; intravesical delivery; Medical research; Medical sciences; Mice; Mice, Nude; Nephrology. Urinary tract diseases; Oligopeptides - pharmacokinetics; Peptides - pharmacokinetics; polyarginine peptide; Tumor Cells, Cultured; Urinary Bladder - metabolism; Urinary Bladder Neoplasms - metabolism; polyarginine peptide; Nephrology; Urinary system; Peptides; Urinary bladder; cell-permeable peptide; bladder; Intravesical administration; intravesical delivery; Urology
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/j.1464-410X.2011.10185.x

What’s known on the subject? and What does the study add? Efficient transfer of macromolecules such as proteins or nucleic acids or small molecules with charged or hydrophilic properties across cellular membranes is one of the major problems in cell biology and drug delivery. A cell‐permeable peptide, a short peptide with 9–12 amino acids, appears to be a potential carrier for delivering macro‐ or small molecules. Our study unveils a unique cell permeable peptide for developing intravesical therapy of new agent. OBJECTIVE • To test the uptake efficiency of R11, a cell‐permeable peptide (CPP), administered intravesically for effective drug delivery. METHODS • We used an approved in vivo model (an athymic nude mouse model) to test synthetic R11 conjugated with fluorescein isothiocyanate (FITC) at concentrations of 1 nM and 5 nM. Controls received FITC without CPP conjugation. • The mice were instilled with R11 for 30 min and killed 3 or 24 h later to harvest bladders for the measurement of CPP uptake and tissue localization using frozen sections. • Bladder uptake specificity was determined using the mean values of relative FITC intensity with each tissue weight. RESULTS • Although the uptake of R11 varied among the mice, a 2‐ to 6‐fold higher amount of R11 was detected in the bladder at 3 and 24 h after intravesical instillation at 1‐nM or 5‐nM concentrations than was detected in the bladders of each mouse control group or in other organs. • Examination of tissue sections further confirmed the localization of R11 in the lamina propria of the bladder wall. CONCLUSION • Because of its high affinity for the bladder, both systemically as reported in previous studies and after intravesical instillation as reported in the present study, R11 should be further tested in animal models as a delivery vector for agents used in treating bladder diseases.