Doxorubicin-loaded PLGA nanoparticles - a systematic evaluation of preparation techniques and parameters∗

Pieper, Sebastian; Langer, Klaus

doi:10.1016/j.matpr.2017.09.185

Cited by 37 publications

(18 citation statements)

References 6 publications

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“…Additionally, the zeta potential values of PCL particles prepared by SNP, MNP and LNP formulations were −22.40 mV, −21.83 mV, −22.6 mV respectively, which resulted in highly stabilized PCL nanoparticles without particle aggregation based on electrostatic repulsion. 41,48 STH has shear thinning behavior due to electrostatic interactions between negatively charged silicate nanoplatelets and positively charged gelatin. 38 Hence, negatively charged PCL nanoparticles can also interact with gelatin to maintain the shear thinning behavior.…”

Section: Resultsmentioning

confidence: 99%

Injectable shear-thinning hydrogels for delivering osteogenic and angiogenic cells and growth factors

et al. 2018

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Bone nonunion may occur when the fracture is unstable, or blood supply is impeded. To provide an effective treatment for the healing of nonunion defects, we introduce an injectable osteogenic hydrogel that can deliver cells and vasculogenic growth factors. We used a silicate-based shear-thinning hydrogel (STH) to engineer an injectable scaffold and incorporated polycaprolactone (PCL) nanoparticles that entrap and release vasculogenic growth factors in a controlled manner. By adjusting the solid composition of gelatin and silicate nanoplatelets in the STH, we defined optimal conditions that enable injection of STHs, which can deliver cells and growth factors. Different types of STHs could be simultaneously injected into 3D constructs through a single extrusion head composed of multiple syringes and needles, while maintaining their engineered structure in a continuous manner. The injected STHs were also capable of filling any irregularly shaped defects in bone. Osteogenic cells and endothelial cells were encapsulated in STHs with and without vasculogenic growth factors, respectively, and when co-cultured, their growth and differentiation were significantly enhanced compared to cells grown in monoculture. This study introduces an initial step of developing a new platform of shape-tunable materials with controlled release of angiogenic growth factors by utilizing PCL nanoparticles.

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Section: Resultsmentioning

confidence: 99%

Injectable shear-thinning hydrogels for delivering osteogenic and angiogenic cells and growth factors

et al. 2018

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“…In contrast, DOX payload in other type of nanoparticles (NPs) such as polymeric NPs is not as high. For example, DOX payload in poly lactic-co-glycolic acid (PLGA) NPs was less than 15 wt.%, whatever the preparation method [ 34 ]. Moreover, DOX payload in the commercial Doxil ® (doxorubicin loaded liposome) was around 12 wt.% [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Doxorubicin-Loaded Metal-Organic Frameworks Nanoparticles with Engineered Cyclodextrin Coatings: Insights on Drug Location by Solid State NMR Spectroscopy

Porcino

Qiu

et al. 2021

Nanomaterials

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Recently developed, nanoscale metal-organic frameworks (nanoMOFs) functionalized with versatile coatings are drawing special attention in the nanomedicine field. Here we show the preparation of core–shell MIL-100(Al) nanoMOFs for the delivery of the anticancer drug doxorubicin (DOX). DOX was efficiently incorporated in the MOFs and was released in a progressive manner, depending on the initial loading. Besides, the coatings were made of biodegradable γ-cyclodextrin-citrate oligomers (CD-CO) with affinity for both DOX and the MOF cores. DOX was incorporated and released faster due to its affinity for the coating material. A set of complementary solid state nuclear magnetic resonance (ssNMR) experiments including 1H-1H and 13C-27Al two-dimensional NMR, was used to gain a deep understanding on the multiple interactions involved in the MIL-100(Al) core–shell system. To do so, 13C-labelled shells were synthesized. This study paves the way towards a methodology to assess the nanoMOF component localization at a molecular scale and to investigate the nanoMOF physicochemical properties, which play a main role on their biological applications.

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“…Nanoparticle preparation via solvent displacement was performed modified after Murakami et al [13] as previously described by Pieper and Langer [34]. 60 mg polymer were dissolved in 2 mL acetone and combined with 200 µL methanolic doxorubicin solution (2.5 mg/mL).…”

Section: Methodsmentioning

confidence: 99%

“…The resulting nanoparticles were compared by particle diameter, polydispersity index, zeta potential, drug load, and drug release behaviour. Preliminary results on the preparation of doxorubicin-loaded PLGA nanoparticles have been previously published [34]. Selected preparations were tested for anticancer efficacy in cancer cell lines, including cell lines that express ABCB1.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of doxorubicin in different polymer nanoparticles and their anticancer activity

Pieper¹,

Onafuye²,

Mulac³

et al. 2019

Beilstein J. Nanotechnol.

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Background: Nanoparticles are under investigation as carrier systems for anticancer drugs. The expression of efflux transporters such as the ATP-binding cassette (ABC) transporter ABCB1 is an important resistance mechanism in therapy-refractory cancer cells. Drug encapsulation into nanoparticles has been shown to bypass efflux-mediated drug resistance, but there are also conflicting results. To investigate whether easy-to-prepare nanoparticles made of well-tolerated polymers may circumvent transporter-mediated drug efflux, we prepared poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) nanoparticles loaded with the ABCB1 substrate doxorubicin by solvent displacement and emulsion diffusion approaches and assessed their anticancer efficiency in neuroblastoma cells, including ABCB1-expressing cell lines, in comparison to doxorubicin solution. Results: The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement led to the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH 7 reaching 53 µg doxorubicin/mg nanoparticle. These PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH 7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anticancer effects. However, nanoparticle-encapsulated doxorubicin did not display increased efficacy in ABCB1-expressing cells relative to doxorubicin solution. Conclusion: Doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anticancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anticancer efficacy. The design of drug-loaded nanoparticles with optimised anticancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anticancer therapy. Further research is required to understand under which circumstances nanoparticles can be used to overcome efflux-mediated resistance in cancer cells.

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Doxorubicin-loaded PLGA nanoparticles - a systematic evaluation of preparation techniques and parameters∗

Cited by 37 publications

References 6 publications

Injectable shear-thinning hydrogels for delivering osteogenic and angiogenic cells and growth factors

Injectable shear-thinning hydrogels for delivering osteogenic and angiogenic cells and growth factors

Doxorubicin-Loaded Metal-Organic Frameworks Nanoparticles with Engineered Cyclodextrin Coatings: Insights on Drug Location by Solid State NMR Spectroscopy

Incorporation of doxorubicin in different polymer nanoparticles and their anticancer activity

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