Sustained release and stabilization of therapeutic antibodies using amphiphilic polyanhydride nanoparticles

Carrillo-Conde, Brenda; Darling, Ross; Seiler, Steven J.; Ramer‐Tait, Amanda E.; Wannemuehler, Michael J.; Narasimhan, Balaji

doi:10.1016/j.ces.2014.08.015

Cited by 27 publications

(34 citation statements)

References 44 publications

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“…In vitro release profiles showed that this delivery system slowly released 40 to 80% of the loaded anti-TNFα antibody over a time window of 4 weeks. Carrillo-Conde et al used poly-anhydride nanoparticles for the delivery of active anti-TNFα monoclonal antibodies [52]. Using a very extensive set of in vitro and in vivo (mouse model) assays, the authors demonstrated that these nanoparticles preserved the biological activity and functionality of the antibody and provided an effective vehicle to control its release kinetics for relatively extended periods of time (up to 20-30 days).…”

Section: Delivering Molecules To Control Macrophage Polarizationmentioning

confidence: 99%

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

Álvarez

Liu

Santiago

et al. 2016

Journal of Controlled Release

201

119

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Macrophages are key players in many physiological scenarios including tissue homeostasis. In response to injury, typically the balance between macrophage sub-populations shifts from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory). In tissue engineering scenarios, after implantation of any device, it is desirable to exercise control on this M1-M2 progression and to ensure a timely and smooth transition from the inflammatory to the healing stage. In this review, we briefly introduce the current state of knowledge regarding macrophage function and nomenclature. Next, we discuss the use of controlled release strategies to tune the balance between the M1 and M2 phenotypes in the context of tissue engineering applications. We discuss recent literature related to the release of anti-inflammatory molecules (including nucleic acids) and the sequential release of cytokines to promote a timely M1-M2 shift. In addition, we describe the use of macrophages as controlled release agents upon stimulation by physical and/or mechanical cues provided by scaffolds. Moreover, we discuss current and future applications of “smart” implantable scaffolds capable of controlling the cascade of biochemical events related to healing and vascularization. Finally, we provide our opinion on the current challenges and the future research directions to improve our understanding of the M1-M2 macrophage balance and properly exploit it in tissue engineering and regenerative medicine applications.

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Section: Delivering Molecules To Control Macrophage Polarizationmentioning

confidence: 99%

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

Álvarez

Liu

Santiago

et al. 2016

Journal of Controlled Release

201

119

View full text Add to dashboard Cite

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“…At the end, the release medium was completely removed and the NPs collected were incubated with 1 mL of 14 mM NaOH for 7 days in order to induce polymer degradation and to completely extract the not-released amount of TZ. 28 The total loaded amount of TZ was calculated as the sum of TZ released and TZ extracted after the release test. The TZ encapsulation efficiency (EE%) and relative drug content (DC%) were calculated as follows: …”

mentioning

confidence: 99%

Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles

Colzani¹,

Pandolfi²,

Hoti³

et al. 2018

IJN

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Background We report the development of an efficient antibody delivery system for the incorporation of trastuzumab (TZ) into poly(lactic- co -glycolic) acid nanoparticles (PLGA NPs). The aim of the work was to overcome the current limitations in the clinical use of therapeutic antibodies, including immunogenicity, poor pharmacokinetics, low tumor penetration and safety issues. Materials and methods Trastuzumab-loaded PLGA NPs (PLGA-TZ) were synthesized according to a double emulsion method. The same protocol was used to produce control batches of nonspecific IgG-loaded NPs and empty PLGA NPs. After release of TZ from PLGA NPs, the effects on the main biological activities of the antibody were evaluated on SKBR3 (human epidermal growth factor receptor 2 [HER2]-positive breast cancer cell line), including specific binding to HER2, phosphorylation of HER2 (Y1248), degradation of HER2 protein and antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. In addition, an MTT assay was performed for treating SKBR3 cells with PLGA NPs loaded with TZ and doxorubicin to evaluate the cytotoxic activity of the combined treatment. Results and discussion TZ was gradually released in a prolonged way over 30 days. The physical characterization performed with circular dichroism, Fourier transform infrared and fluorescence spectroscopy of TZ after release demonstrated that no structural alterations occurred compared to the native antibody. In vitro experiments using SKBR3 cells showed that TZ released from PLGA NPs maintained the same biological activity of native TZ. PLGA NPs allowed a good co-encapsulation efficiency of TZ and doxorubicin resulting in improved therapy. Conclusion With the TZ case study, we demonstrate that the distinctive features of therapeutic monoclonal antibodies, including molecular targeting efficiency, capability to inhibit or properly affect the regulatory signaling pathways of cancer cells and stimulation of the ADCC, are fully preserved after loading into and release from PLGA NPs. In addition, PLGA NPs are shown to allow for the simultaneous incorporation of TZ and conventional chemotherapeutics, resulting in a potent antitumor nanodrug well suited for in situ combination and neoadjuvant therapy.

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“…At the conclusion of the release experiment, 40 mM sodium hydroxide was used to extract remaining encapsulated drug and this information was used to calculate the drug encapsulation efficiency, as previously described. 21 RhoB and CBB release in acidic conditions were similarly assayed by incubating particles in 0.1 M acetate buffer, pH 4.3 for one week, followed by base extraction. Mass drug released was quantified via fluorescence (RhoB,  ex 553 nm,  em 627 nm) and absorbance (CBB, PBS and acetate buffer  abs 580 nm, NaOH  abs 590 nm) spectrophotometry (SpectraMax M3, Molecular Devices, San Jose, CA) in 96-well plates.…”

Section: Drug Release Kineticsmentioning

confidence: 99%

High-Throughput Synthesis and Screening of Rapidly Degrading Polyanhydride Nanoparticles

2020

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Combinatorial techniques can accelerate the discovery and development of polymeric nanodelivery devices by pairing high-throughput synthesis with rapid materials characterization. Biodegradable polyanhydrides demonstrate tunable release, high cellular internalization, and dose sparing properties when used as nanodelivery devices. This nanoparticle platform shows promising potential for small molecule drug delivery, but the pace of understanding and rational design of these nanomedicines is limited by the low throughput of conventional characterization. This study reports the use of a highthroughput method to synthesize libraries of a newly synthesized, rapidly-eroding polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and sebacic acid (SA) monomers. The high-throughput method enabled efficient screening of copolymer microstructure, revealing weak block-type and alternating architectures. The high-throughput method was adapted to synthesize nanoparticle libraries encapsulating hydrophobic model drugs. Drug release from these nanoparticles was rapid, with a majority of the payload released within three days. Drug release was dramatically slowed at acidic pH, which could be useful for oral drug delivery. Rhodamine B (RhoB) release kinetics generally followed patterns of polymer erosion kinetics, while Coomassie brilliant blue (CBB) released the fastest from the slowest degrading polymer chemistry and vice versa. These differences in trends between copolymer chemistry and release kinetics were hypothesized to arise from differences in mixing thermodynamics. A high-throughput method was developed to synthesize polymerdrug film libraries and characterize mixing thermodynamics by melting point depression. Rhodamine B had a negative χ for all copolymers tested, indicating a tendency toward miscibility. By contrast, CBB χ increased, eventually becoming positive, with increasing CPTEG content. This indicates an increasing tendency toward phase separation in CPTEG-rich copolymers. These in vitro results screening polymerdrug interactions showed good agreement with in silico predictions from Hansen solubility parameter estimation and were able to explain the observed differences in model drug release trends. ABSTRACTCombinatorial techniques can accelerate the discovery and development of polymeric nanodelivery devices by pairing high-throughput synthesis with rapid materials characterization.Biodegradable polyanhydrides demonstrate tunable release, high cellular internalization, and dose sparing properties when used as nanodelivery devices. This nanoparticle platform shows promising potential for small molecule drug delivery, but the pace of understanding and rational design of these nanomedicines is limited by the low throughput of conventional characterization.This study reports the use of a high-throughput method to synthesize libraries of a newly synthesized, rapidly-eroding polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and sebacic acid (SA) monomers. T...

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Sustained release and stabilization of therapeutic antibodies using amphiphilic polyanhydride nanoparticles

Cited by 27 publications

References 44 publications

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles

High-Throughput Synthesis and Screening of Rapidly Degrading Polyanhydride Nanoparticles

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