Beaded Plasma Clot: a Potent sustained-release, drug-delivery System

Abstract

Aim: The aim of the study was to prepare a drug-entrapped, beaded form of blood plasma for possible sustained drug delivery. Method: Blood plasma mixed with various drugs was enriched with CaCl2 and transferred in the form of small droplets on to a glass slide covered with parafilm. Clot formation was induced by incubation at 37°C. Results: Plasma-bead entrapped tetracycline, amphotericin B and daunorubicin were released gradually in vitro. Crosslinking of the beads with glutaraldehyde decreased the release rate of drugs remarkably. The plasma bead-entrapped cefotaxime administered subcutaneously in mice was released in a slow and sustained fashion and remained in circulation for a longer duration than the antibiotic administered in the free form. Conclusion: The plasma beads have potential for the sustained delivery of drugs in vivo, since their preparation does not require additional thrombin or other proteins and can be readily accomplished by using autologous plasma, thereby minimizing the risk of immunological complications.

Fibrin matrices: The versatile therapeutic delivery systems

“…The PB preprations were leaky for daunorubicin and tetracycline but release of amphotericin B was remarkably slow, apparently because of the binding of the antifungal to the bead proteins [104,105]. Release rates of PBentrapped drugs could be markedly lowered by treating the PBs with glutaraldehyde [36]. The in vivo release of PB-entrapped cefotaxime injected subcutaneously in the Swiss mice was slow and Page 13 of 51 A c c e p t e d M a n u s c r i p t 13 sustained; cefotaxime administered in the fibrin formulation was detectable in circulation even after 144 h, while in those receiving the free drug, no drug was detectable beyond 108 h. The remarkable advantages of the PBs and PMPs include the possibility of using autologous plasma, non-requirement of fibrinogen purification, as well as extraneous thrombin or transglutaminase.…”

“…These include Fibrin Microbeads (FMB) [29], Fibrin Films (FF) [30], Fibrin Discs (FD) [31], Fibrin Threads (FT) [32], Fibrin Microparticles (FMP) [33] Fibrin Nanoparticles (FNP) [34] and Fibrin Nano Constructs (FNC) [35]. More recently, whole blood plasma, induced to clot with help of endogenous thrombin and transglutaminase and formulated as plasma beads (PB) or plasma microparticles (PMPs), has also been studied for its therapeutic delivery potential [36,37]. Pharmaceutical-entrapped fibrin matrices may also be created in situ by injecting mixtures of fibrinogen, the pharmaceutical and thrombin [38].…”

“…PBs were prepared by adding CaCl 2 to plasma isolated from blood collected in presence of EDTA and rapidly distributing the calcium-enriched plasma in the form of droplets with a multi chanel micropipette on a Parafilm surface [36]. Alteranatively, plasma could be converted to PMPs by stirring the calcium-enriched plasma in mineral oil [37] (Fig.…”

“…Transforming Growth Factor β1 [10,11] Platelet-Derived Growth Factors (PDGF-BB, AB) [12,13] Insuline Like Growth Factor (IGF-1) [12] Interleukin-1β [14] Epidermal Growth Factor (EGF) [15] Enzymes/proenzymes Plasminogen [16] Tissue Plasminogen Activator (tPA) [16] Plasminogen Activator Inhibitor [17] Thrombin [18] Neomycin, Gentamicin, Polymyxin E in vitro [81] Cephalotin in vitro and in vivo [82] Cefotaxime in vivo [83] Metranidazole, Bacitracine in vivo [84] Cefoxitin, Gentamicin in vivo [85] Tobramycin in vitro and in vivo [86] Gentamicin derivative in vitro and in vivo [87] Ceftazydime,Tobramycin, Gentamicin,Clindamycin, Ampicillin in vitro [88] Teicoplanin,Ciproflaxacin, Cefoxitin, Gentamicin in vitro [89] Gentamycin derivative in vitro and in vivo [90] Clindamycin, Cefotaxime in vivo [91] Sisomicin in vivo [92] Neomycine in vivo [93] Cifroflaxacin in vitro and in vivo [94] Ampicillin, Debakacin, Gentamicin, Carbenicillin, Ceftazidin, Cefoxitin, Cefoxitin, Polymixin B, Mupirocin, Norflaxacin,Clindamycin,Nitrofurazone in vitro [95] Oflaxacin, Ampicillin, Gentamicin in vitro [96] Abrekacin sulfate in vitro and in vivo [97] Vancomycin, Cephalothin, Gentamicin, Teicoplanin in vitro and in vivo [98] Tetracyclin in vivo [58] Tetracyclin in vitro and in vivo [31] Tetracyclin in vitro [36] Ceftazidime, Moxifloxacin, Lomefloxacin,Vancomycin in vivo [99] Vancomycin in vivo [100] …”

Plasma Bead Entrapped Liposomes as a Potential Drug Delivery System to Combat Fungal Infections

“…We have reported a procedure for the preparation of plasma beads (PB) from autologous plasma, necessitating the addition of no exogenous enzymes/proteins, with remarkable potential for sustained drug/antigen delivery [ 22 , 23 , 24 ]. In this paper, we report the use of plasma-alginate composite matrices, fibrinolytic inhibitors (aprotinin and 6-amino caproic acid) as well as dual delivery via various liposomal formulations to achieve superior sustained release of entrapped molecules in PB.…”