Drug Loaded Erythrocytes: As Novel Drug Delivery System

Patel, Paresh D.; Dand, Neha; Hirlekar, Rajashree; Vj, Kadam

doi:10.2174/138161208783330772

Cited by 53 publications

(22 citation statements)

References 44 publications

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“…5B-5D also confirms only minor morphological perturbations to the SSRBCs following hypotonic pre-swelling loading of calcein. The calcein entrapment efficiency, determined by flow cytometry measurements of the fraction of cells detected with measureable fluorescence compared to all counted cells, was about 85% which is consistent with reported loading efficiencies for this method in nRBCs [25-26]. …”

Section: Resultssupporting

confidence: 87%

Drug-loaded sickle cells programmed ex vivo for delayed hemolysis target hypoxic tumor microvessels and augment tumor drug delivery

Choe

Terman²,

Rivers

et al. 2013

Journal of Controlled Release

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Selective drug delivery to hypoxic tumor niches remains a significant therapeutic challenge that calls for new conceptual approaches. Sickle red blood cells (SSRBCs) have shown an ability to target such hypoxic niches and induce tumoricidal properties when used together with exogenous pro-oxidants. Here we determine whether the delivery of a model therapeutic encapsulated in murine SSRBCs can be enhanced by ex vivo photosensitization under conditions that delay autohemolysis to a time that coincides with maximal localization of SSRBCs in a hypoxic tumor. Hyperspectral imaging of 4T1 carcinomas shows oxygen saturation levels <10% in a large fraction (commonly 50% or more) of the tumor. Using video microscopy of dorsal skin window chambers implanted with 4T1 tumors, we demonstrate that allogeneic SSRBCs, but not normal RBCs (nRBCs), selectively accumulate in hypoxic 4T1 tumors between 12-24 hours after systemic administration. We further show that ex vivo photo-oxidation can program SSRBCs to postpone hemolysis/release of a model therapeutic to a point that coincides with their maximum sequestration in hypoxic tumor microvessels. Under these conditions, drug-loaded photosensitized SSRBCs show a 3-4 fold greater drug delivery to tumors compared to non-photosensitized SSRBCs, drug-loaded photosensitized nRBCs, and free drug. These results demonstrate that photo-oxidized SSRBCs, but not photo-oxidized nRBCs, sequester and hemolyze in hypoxic tumors and release substantially more drug than photo-oxidized nRBCs and non-photo-oxidized SSRBCs. Photo-oxidation of drug-loaded SSRBCs thus appears to exploit the unique tumor targeting and carrier properties of SSRBCs to optimize drug delivery to hypoxic tumors. Such programmed and drug-loaded SSRBCs therefore represent a novel and useful tool for augmenting drug delivery to hypoxic solid tumors.

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Section: Resultssupporting

confidence: 87%

Drug-loaded sickle cells programmed ex vivo for delayed hemolysis target hypoxic tumor microvessels and augment tumor drug delivery

Choe

Terman²,

Rivers

et al. 2013

Journal of Controlled Release

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“…This resealing procedure has been widely used by other researchers over the years with MERs. 23,24 At the end of this process, the NERs are expected to have intact, sealed membranes. At this point, while the NERs are loaded with solute, free solute is also present in the external solution.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Colloidal Properties of Nanoerythrosomes Derived from Bovine Red Blood Cells

Kuo

Hoang

et al. 2015

Langmuir

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Liposomes are nanoscale containers that are typically synthesized from lipids using a high-shear process such as extrusion or sonication. While liposomes are extensively used in drug delivery, they do suffer from certain problems including limited colloidal stability and short circulation times in the body. As an alternative to liposomes, we explore a class of container structures derived from erythrocytes (red blood cells). The procedure involves emptying the inner contents of these cells (specifically hemoglobin) and resuspending the empty structures in buffer, followed by sonication. The resulting structures are termed nanoerythrosomes (NERs), i.e., they are membrane-covered nanoscale containers, much like liposomes. Cryo-transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS) are employed for the first time to study these NERs. The results reveal that the NERs are discrete spheres (∼110 nm diameter) with a unilamellar membrane of thickness ∼4.5 nm. Remarkably, the biconcave disc-like shape of erythrocytes is also exhibited by the NERs under hypertonic conditions. Moreover, unlike typical liposomes, NERs show excellent colloidal stability in both buffer as well as in serum at room temperature, and are also able to withstand freeze-thaw cycling. We have explored the potential for using NERs as colloidal vehicles for targeted delivery. Much like conventional liposomes, NER membranes can be decorated with fluorescent or other markers, solutes can be encapsulated in the cores of the NERs, and NERs can be targeted to specifically bind to mammalian cells. Our study shows that NERs are a promising and versatile class of nanostructures. NERs that are harvested from a patient's own blood and reconfigured for nanomedicine can potentially offer several benefits including biocompatibility, minimization of immune response, and extended circulation time in the body.

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“…For example, red blood cell membranes have been used to coat NPs as well as to generate nanovesicles with liposome-like features in terms of drug loading and release capabilities [154,158]. Hu et al demonstrated that red blood cell molecules were correctly transferred and oriented on the NPs surfaces [159].…”

Section: Evading the Immune Systemmentioning

confidence: 99%

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

Corbo

Molinaro

Parodi

et al. 2015

Nanomedicine (Lond.)

556

443

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In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP–PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.

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Drug Loaded Erythrocytes: As Novel Drug Delivery System

Cited by 53 publications

References 44 publications

Drug-loaded sickle cells programmed ex vivo for delayed hemolysis target hypoxic tumor microvessels and augment tumor drug delivery

Drug-loaded sickle cells programmed ex vivo for delayed hemolysis target hypoxic tumor microvessels and augment tumor drug delivery

Colloidal Properties of Nanoerythrosomes Derived from Bovine Red Blood Cells

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

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