Comparison of Uricase-Bound and Uricase-Loaded Erythrocytes as Bioreactors for Uric Acid Degradation

Magnani, Mauro; Mancini, Umberto; Bianchi, Marzia; Fazi, Antonio

doi:10.1007/978-1-4615-3030-5_23

Cited by 18 publications

(11 citation statements)

References 5 publications

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“…In addition, coupling of drugs to RBC surface circumvents issues related to drug release (approaches to trigger drug release by using controlled lysis by complement have been suggested, yet practically useful controlled release from carrier RBC remains an elusive goal)28. Of note, coupling to RBC surface resolves diffusional limitations: even enzymes that react with small, membrane permeable substrate are more active when bound to the RBC surface than when incorporated within the cell145. Further, surface coupling offers a unique option to load drugs on circulating RBC without technically and logistically cumbersome need for their extraction necessary for drug encapsulation and re-infusion.…”

Section: Coupling Therapeutics To the Rbc Surfacementioning

confidence: 99%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

342

294

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Importance of the field-Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBCencapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field.Areas covered by this review-Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC.What the reader will gain-The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery.Take home message-RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system.

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Section: Coupling Therapeutics To the Rbc Surfacementioning

confidence: 99%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

342

294

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“…Blood samples (about 500 µL) were drawn from the posterior orbital venous plexus at indicated times (3,5,7,9, and 12 hours) and incubated at 37°C for 20 minutes. Next, the blood samples were centrifuged at 3000 rpm for 10 minutes and the uric acid in the plasma was measured using Uric Acid Assay Kit (C012) (Nanjing Jiancheng Bioengineering Institute, Nanjing, China).…”

Section: Pharmacodynamic Studymentioning

confidence: 99%

“…2 However, the clinical application of uricase has been limited due to its undesirable biological properties (ie, premature degradation and inactivation by endogenous proteases, elimination by the reticuloendothelial system, immunogenicity, and toxic side effects caused by the host immune system reacting toward foreign proteins). 3 To overcome these enzymatic problems, a variety of uricase preparations, such as polyethylene glycol (PEG) uricase, 4 alginate-microencapsulated uricase, 5 dextran-PEG-coupled uricase, 6 and erythrocyte-encapsulated uricase 7 have been developed. Nevertheless, these vesicles have some shortcomings, such as enzyme deactivation during immobilization reactions, the physical instability of the carriers when oxygen bubbles are produced, and the readiness of the uricase to fall off the vesicles.…”

Section: Introductionmentioning

confidence: 99%

Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes

Tan¹,

Zhang²,

Wang³

et al. 2012

IJN

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Objective: Previous studies on various enzymosomes (functional lipid vesicles encapsulating an enzyme) have been mostly carried out in vitro and have focused on preserving catalytic activity and improving the stability of the enzyme. Until now, few studies have focused on their in vivo fate. Similarly, although we have previously reported the increased in vitro uricolytic activity (about 2.2 times higher than that of free uricase, or three times higher than that of PEGylated uricase, Puricase ® , under physiological pH and temperature) and improved stability of the novel alkaline enzymosomes (functional lipid vesicles encapsulating uricase from Candida utilis: uricase-containing lipid vesicles, UOXLVs), it is still necessary to study the biological properties and hypouricemic effects of UOXLVs in vivo. Methods:The enzyme kinetics, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary safety of UOXLVs were evaluated. Results: The Michaelis constant (K m ) value of the UOXLVs was slightly lower than that of the free enzyme. The enzyme release from the UOXLVs lasted over 12 hours and their circulation half-life was about sevenfold longer than that of the free uricase. Meanwhile, the UOXLVs had a 22-fold increase in the area under the curve compared with the free uricase. Furthermore, it took less than 3 hours for the UOXLVs to lower the plasma uric acid concentration from a high to a normal level, compared with 6 hours for the free uricase. In addition, the UOXLVs had much less immunogenicity than free uricase and were well tolerated by all animals throughout the observation period. Conclusion:The UOXLVs markedly improved the biological properties and enhanced the hypouricemic effects of uricase in vivo.

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“…With this approach, the RBC membrane is no longer a barrier for the surface-bound enzymes and other agents. Experimental data confirmed that drugs, including enzymes, coupled to RBC surface are more accessible and active compared with encapsulated counterparts [102,103]. …”

Section: Coupling Therapeutics To the Rbc Surface: Prototype Studiesmentioning

confidence: 95%

Delivery of Drugs Bound to erythrocytes: New Avenues for an Old Intravascular Carrier

et al. 2015

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For several decades, researchers have used erythrocytes for drug delivery of a wide variety of therapeutics in order to improve their pharmacokinetics, biodistribution, controlled release and pharmacodynamics. Approaches include encapsulation of drugs within erythrocytes, as well as coupling of drugs onto the red cell surface. This review focuses on the latter approach, and examines the delivery of red blood cell (RBC)-surface-bound anti-inflammatory, anti-thrombotic and anti-microbial agents, as well as RBC carriage of nanoparticles. Herein, we discuss the progress that has been made in surface loading approaches, and address in depth the issues relevant to surface loading of RBC, including intrinsic features of erythrocyte membranes, immune considerations, potential surface targets and techniques for the production of affinity ligands.

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Comparison of Uricase-Bound and Uricase-Loaded Erythrocytes as Bioreactors for Uric Acid Degradation

Cited by 18 publications

References 5 publications

Drug delivery by red blood cells: vascular carriers designed by mother nature

Drug delivery by red blood cells: vascular carriers designed by mother nature

Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes

Delivery of Drugs Bound to erythrocytes: New Avenues for an Old Intravascular Carrier

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