Acute kidney injury (AKI) is an emergent public health problem that affects millions of patients worldwide. Several pharmacologic therapies that can accelerate recovery and improve survival were successful in experimental models but failed to manifest any significant beneficial effect in clinical practice [1]. Recent studies have indicated that adult renal stem/progenitor cells (ARPCs) are able to repair damaged renal proximal tubular epithelial cells (RPTECs) in AKI induced by toxic agents, via the secretion of both inhibin-A (INHB-A), FGF2 chemokines and specific microvesicle-vehicled mRNA [2]. Our goal was to synthesize a natural polymer-based nanosystem for efficacious delivery of INHB-A. Alginate (AL) and chitosan (CS), due to their promising properties are being exploited for the development of drug delivery systems [3]. INHB-Aloaded Polysaccharides Synthetic Vesicles (INHB-A-PSSV) were synthesized by two steps methods: ionotropic pre-gelation of AL core, followed by CS polyelectrolyte complexation. A microfluidic device was appositely fabricated in order to optimize the INHB-PSSV -at interface-assembly process, in terms of polymers and INHB-A working amount as well as vesicles size distribution. TEM and DLS characterization showed highly mono-disperse spherical PSSV ((157 ± 30) nm in diameter) and ?-potential measurement ((+56 ± 4) mV) confirmed the CS coating stability. Cellular uptake and INHB-A-PSSV effectiveness were tested in an in vitro model of cisplatin (CisPt) induced cell toxicity. RPTECs were exposed to 2.5 µmol/l CisPt for 6 h and, after drug withdrawal, cell viability was performed at 3 days after treatment. CisPt treated cell viability significantly decreased, compared with healthy control. We showed that addition of INHB-A-PSSV to CisPt -treated RPTECs led to a substantial increase in cell number and viability after 3 days of culture. Remarkably, a very low dosage of functional loaded protein (8 ng/25 µl) was sufficient to induce cell regeneration and the percentage of viable cells was similar to that of RPTECs without CisPt treatment.
Alginate-Chitosan synthetic vesicles as a promising Inhibin-A delivery system for acute kidney injury therapy
A Aloisi;C C Toma;R Rinaldi
2015
Abstract
Acute kidney injury (AKI) is an emergent public health problem that affects millions of patients worldwide. Several pharmacologic therapies that can accelerate recovery and improve survival were successful in experimental models but failed to manifest any significant beneficial effect in clinical practice [1]. Recent studies have indicated that adult renal stem/progenitor cells (ARPCs) are able to repair damaged renal proximal tubular epithelial cells (RPTECs) in AKI induced by toxic agents, via the secretion of both inhibin-A (INHB-A), FGF2 chemokines and specific microvesicle-vehicled mRNA [2]. Our goal was to synthesize a natural polymer-based nanosystem for efficacious delivery of INHB-A. Alginate (AL) and chitosan (CS), due to their promising properties are being exploited for the development of drug delivery systems [3]. INHB-Aloaded Polysaccharides Synthetic Vesicles (INHB-A-PSSV) were synthesized by two steps methods: ionotropic pre-gelation of AL core, followed by CS polyelectrolyte complexation. A microfluidic device was appositely fabricated in order to optimize the INHB-PSSV -at interface-assembly process, in terms of polymers and INHB-A working amount as well as vesicles size distribution. TEM and DLS characterization showed highly mono-disperse spherical PSSV ((157 ± 30) nm in diameter) and ?-potential measurement ((+56 ± 4) mV) confirmed the CS coating stability. Cellular uptake and INHB-A-PSSV effectiveness were tested in an in vitro model of cisplatin (CisPt) induced cell toxicity. RPTECs were exposed to 2.5 µmol/l CisPt for 6 h and, after drug withdrawal, cell viability was performed at 3 days after treatment. CisPt treated cell viability significantly decreased, compared with healthy control. We showed that addition of INHB-A-PSSV to CisPt -treated RPTECs led to a substantial increase in cell number and viability after 3 days of culture. Remarkably, a very low dosage of functional loaded protein (8 ng/25 µl) was sufficient to induce cell regeneration and the percentage of viable cells was similar to that of RPTECs without CisPt treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
