Combination therapy using fibrinogen γ‐chain peptide‐coated, ADP‐encapsulated liposomes and hemoglobin vesicles for trauma‐induced massive hemorrhage in thrombocytopenic rabbits

Abstract

BACKGROUND: We previously developed substitutes for red blood cells (RBCs) and platelets (PLTs) for transfusion. These substitutes included hemoglobin vesicles (HbVs) and fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, adenosine diphosphate (ADP)-encapsulated liposomes [H12-(ADP)liposomes]. Here, we examined the efficacy of combination therapy using these substitutes instead of RBC and PLT transfusion in a rabbit model with traumainduced massive hemorrhage with coagulopathy. ABBREVIATIONS: ADP = adenosine diphosphate; APTT = activated partial thromboplastin time; AT = antithrombin; CR = clot rate; CT = clotting time; HbVs = hemoglobin vesicles; HSA = human serum albumin; MAP = mannitol adenine phosphate; NO = nitric oxide; NOx = NO 2 − /NO 3 ; PPP = plateletpoor plasma; PRP = platelet-rich plasma; PT = prothrombin time.From the

Generation and manipulation of human iPSC-derived platelets

“…As an alternative to these donor-dependent blood product supply systems, biosynthesized blood products have been created by introducing molecules into liposomes and other platform materials to mimic the function of red blood cells or platelets [16][17][18]. These products are expected to have advantages in emergency situations with limited logistics, such as trauma at battlefields, owing to better preservation capacity, but it is especially difficult to recapitulate the delicate and complicated functional properties of native platelets.…”

Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer

“…According to numerous animal studies, Hb-V potentially exhibits a favorable safety profile, including blood compatibility (no platelet and complement activation) and lack of tissue damage, nephrotoxicity, and hypertension, even if repeatedly administered at high doses. 3) Furthermore, as summarized in Table 1, it exhibited well-defined pharmacokinetic characteristics such as blood retention; distribution, metabolic, and excretion profiles; the influence of accelerated blood clearance phenomenon; and drug-interaction with CYP [6][7][8][9][10][11][12][13][14][15][16][17] . On the basis of accumulated evidence, some basic research has been conducted to investigate the possibility that Hb-V can be applied as an oxygen carrier against various ischemic or hypoxic disorders such as hemorrhagic shock, 18) brain ischemia, 19) and pre-eclampsia.…”

“…14,15) Hb-V slightly inhibits the metabolic activity of hepatic CYP; however, the metabolic activity recovers within 7 d of administration. 16,17) beneficial effects such as anti-apoptosis, anti-inflammatory, and anti-oxidative effects in mammalian species, 21) incentivizing researchers to develop CO-based pharmaceutical preparations. Under physiological conditions, most of the endogenous CO, which is produced in the body as a byproduct during the metabolism of heme by heme oxygenase, 22) is scavenged and carried by hemoglobin inside red blood cells, implying that red blood cells can be utilized as inherent carriers of CO. 23) In fact, it has been reported that exogenously supplied CObound red blood cells function as CO donors.…”

Convergence of the Technologies of the Fourth Industrial Revolution and the Systematic Consequences for the Economies and Societies (Part 1)

“…През 2019 г. обаче вече стана ясно, че изследователи от Тел-Авивския университет успешно вече са отпечатали първото в света триизмерно сърце с помощта на 3D принтер и използване на собствени клетки на пациента и биологически материали, за да съответства то изцяло на имунологичните, клетъчни, биохимични и анатомични свойства на пациента, нуждаещ се евентуално от изкуствено сърце (Matthieussent, 2019). Колектив от учени от Медицинския колеж към Министерството на отбраната в Япония пък създаде из-куствена кръв, която може да бъде вкарвана у всеки пациент, независимо от кръвната му група (Kinoshita, 2019).…”