Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation

Marco, Maria Di

doi:10.2147/ijn.s6458

Cited by 47 publications

(57 citation statements)

References 159 publications

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“…The electrospinning parameter flow rate has an impact on material manufacturing time and we demonstrated successful protein loading into electrospun fibers at both flow rates tested. The high encapsulation efficiencies achieved (>95%) using this process also demonstrate the manufacturing advantage of this platform for delivery of biotherapeutics, which can be a limitation of other nanotechnology approaches such as particulate systems (Colletier et al, 2002; Marco et al, 2010). …”

Section: Resultsmentioning

confidence: 97%

Protein-loaded emulsion electrospun fibers optimized for bioactivity retention and pH-controlled release for peroral delivery of biologic therapeutics

Frizzell

Ohlsen

Woodrow

2017

International Journal of Pharmaceutics

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Biologics are the most rapidly growing class of therapeutics, but commonly suffer from low stability. Peroral administration of these therapeutics is an attractive delivery route; however, this route introduces unique physiological challenges that increase the susceptibility of proteins to lose function. Formulation of proteins into biomaterials, such as electrospun fibers, is one strategy to overcome these barriers, but such platforms need to be optimized to ensure protein stability and maintenance of bioactivity during the formulation process. This work develops an emulsion electrospinning method to load proteins into Eudragit® L100 fibers for peroral delivery. Horseradish peroxidase and alkaline phosphatase are encapsulated with high efficiency into fibers and released with pH-specificity. Recovery of protein bioactivity is enhanced through reduction of the emulsion aqueous phase and the inclusion of a hydrophilic polymer excipient. Finally, we show that formulation of proteins in lyophilized electrospun fibers extends the therapeutic shelf life compared to aqueous storage. Thus, this platform shows promise as a novel dosage form for the peroral delivery of biotherapeutics.

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Section: Resultsmentioning

confidence: 97%

Protein-loaded emulsion electrospun fibers optimized for bioactivity retention and pH-controlled release for peroral delivery of biologic therapeutics

Frizzell

Ohlsen

Woodrow

2017

International Journal of Pharmaceutics

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“…Vascularly-targeted nanotherapeutics can carry RNAi or DNA to the heart muscle, where delivery of such hydrophilic cargo is otherwise problematic. Yet, the kinetics of transport from liposomes through the endothelium is not well characterized [36]. Therefore, here, we have evaluated the accumulation of targeted liposomes in the heart in models of cardiovascular disease and have tracked the cargo as it enters the endothelium.…”

Section: Discussionmentioning

confidence: 99%

The cargo of CRPPR-conjugated liposomes crosses the intact murine cardiac endothelium

Zhang

Sirish

et al. 2012

Journal of Controlled Release

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Ligand-conjugated liposomes and other nano-sized constructs are attractive drug carriers due to their extended plasma circulation; however, limited data are available as to whether their cargo can traverse the endothelium of solid organs. To determine whether the cargo of endothelially-targeted liposomes is internalized by endothelial cells and transported into tissue, and to evaluate whether such liposomes can accumulate in models of cardiovascular disease, we tracked the fate of the cargo (a hydrophilic fluorescent dye) and shell (conjugated with a radioisotope) of a heart-homing liposome (CRPPR-conjugated). The ex vivo heart was imaged with confocal microscopy and the in vivo heart with positron emission tomography in sham treated mice and models of ischemia/reperfusion (I/R) and myocardial infarction (MI). Within 30 min of injection of 20mg/kg CRPPR-liposomes, fluorescence increased by 47 fold in the tissue surrounding the vascular lumen, as compared with non-targeted liposomes. Both the accumulation on the endothelium and the interstitial fluorescence saturated at an injected dose of 20 mg/kg. In both I/R and MI models, CRPPR-liposomes accumulated in diseased sites, although less than in surrounding healthy tissue. The accumulation in the diseased sites increased with time post injury: the ratio of accumulated radioactivity in the diseased and healthy cardiac tissue increased from 0.20±0.04, to 0.58±0.12 and 0.61±0.19 for 1, 7, and 99 days post MI, indicating the potential for adequate delivery and therapeutic efficacy if the targeted particles are injected at 7 or more days post MI. In summary, CRPPR- liposomes accumulated in normal and diseased hearts, and the cargo accumulated in the tissue within minutes and remained detectable after 24 hours.

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“…Liposomes are prepared by sonication, reverse phase evaporation or fi lm formation [25]. Among different types of liposomes, due to the ease of preparation and low amount of stress applied to the proteins, dehydrated-rehydrated vesicles are most commonly used in protein drug delivery [26]. The liposomes can be easily modifi ed with targeting moieties, e.g.…”

Section: Liposomesmentioning

confidence: 99%

Lipids and inorganic nanoparticles in oral insulin delivery

Sonia¹,

Sharma²

2014

Oral Delivery of Insulin

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Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation

Cited by 47 publications

References 159 publications

Protein-loaded emulsion electrospun fibers optimized for bioactivity retention and pH-controlled release for peroral delivery of biologic therapeutics

Protein-loaded emulsion electrospun fibers optimized for bioactivity retention and pH-controlled release for peroral delivery of biologic therapeutics

The cargo of CRPPR-conjugated liposomes crosses the intact murine cardiac endothelium

Lipids and inorganic nanoparticles in oral insulin delivery

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