Semisynthetic supra plasma expanders

a new class of therapeutics to improve microcircualtion in sickle cell anaemia

Fantao Meng, Dhananjaya Kaul, Sangeetha Thangaswamy, Savita Bhutoria, Gary J. Gerfen, Craig A. Branch, Marcos Intaglietta, Seetharama A. Acharya

Research output: Contribution to journalArticle

Abstract

Compromised microcirculation and endothelial dysfunction are hallmarks of sickle cell disease (SCD). EAF PEG Haemoglobin (Hb) and EAF PEG Albumin (Alb) represent a novel class of semisynthetic colloidal supra plasma expanders that improve microcirculation. The therapeutic activity of supra plasma expanders to attenuate vaso-occlusion and restore the haemodynamic functions in patients with SCD has been investigated using NY1DD, a transgenic mouse model of mild SCD without anaemia. Vaso-occlusion and perturbation of haemodynamics are amplified in NY1DD by hypoxia-reoxygenation protocol. EAF P5K6 Alb and Alb T12 (Alb conjugated with 12 copies of antioxidant tempo) attenuate vaso-occlusion when infused at the start of reoxygenation. However, only EAF PEG Alb restores haemodynamics close to levels in control C57BL. EAF P5K6 Alb-T12, active plasma expander conjugated with antioxidant, completely clears vaso-occlusion and restores normal haemodynamics. EAF PEG Hb also completely clears vaso-occlusion and restores normal haemodynamics. Pretreating NY1DD with EAF PEG Hb protects it from hypoxia reoxygenation-induced damages. EAF P5K6 Alb T12 attenuates the endothelial dysfunction in S + S Antilles mice as reflected by the vasodilatory response of its arteries and arterioles to vaso-dilators. Active plasma expanders are novel therapeutics to restore normal haemodynamics in SCD patients to improve tissue oxygenation during episodes of painful vaso-occlusive crisis. Abbreviations: 2-IT: 2-immothiolane; Mal-T: 4-Maleimido tempo; Alb: human serum albumin (HSA); Alb-T12: human albumin conjugated with 12 copies of tempo; EAF: extension arm facilitated; EAF PEG Hb: extension arm facilitated PEGylated haemoglobin; EAF PEG Alb: extension arm facilitated PEGylated albumin; EAF P3K6 Hb: extension arm facilitated PEGylated haemoglobin conjugated with 6 copies of PEG3K; EAF P5K6 Alb T12: extension arm facilitated PEGylated albumin conjugated with 6 copies of PEG5K and 12 copies of tempo; Hb: haemoglobin; HAS: human serum albumin (Alb); PEG: polyethylene glycol; MP4: MalPEG Hb, is formulated at 4.2 g/dL in lactated Ringer's solution, a product of Sangart; SCD: sickle cell disease; NO: nitric oxide; SEC: size exclusive chromatography; Vrbc: red cell velocity; Q: volumetric flow rates, Q; SNP: sodium nitroprusside.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalArtificial cells, nanomedicine, and biotechnology
Volume47
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Hemoglobin
Sickle Cell Anemia
Albumins
Polyethylene glycols
Plasmas
Hemodynamics
Hemoglobins
Microcirculation
Therapeutics
Antioxidants
Serum Albumin
Oxygenation
Nitric oxide
Chromatography
Thermodynamic properties
Arterioles
Nitroprusside
Cells
Sodium
Flow rate

Keywords

  • anti vaso-occlusion
  • EAF PEGylation
  • plasma expanders
  • sickle cell disease
  • tempo

ASJC Scopus subject areas

  • Biotechnology
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Semisynthetic supra plasma expanders : a new class of therapeutics to improve microcircualtion in sickle cell anaemia. / Meng, Fantao; Kaul, Dhananjaya; Thangaswamy, Sangeetha; Bhutoria, Savita; Gerfen, Gary J.; Branch, Craig A.; Intaglietta, Marcos; Acharya, Seetharama A.

In: Artificial cells, nanomedicine, and biotechnology, Vol. 47, No. 1, 01.12.2019, p. 73-82.

Research output: Contribution to journalArticle

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