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Aim: New envisions are put forward on the cross application of plant extracts and biomaterials, especially new conjectures are put forward on glucose lowering nanodrug delivery systems.
Study design and methods: In this study, pterostilbene (PTE) was esterified with acryloyl chloride firstly, and then 3-acrylamidophenyl boric acid (AAPBA) and PTE esterified by acryloyl chloride were copolymerized into p(AAPBA-b-PTE). The characterization and structure of its polymer were examined. Additionally, p(AAPBA-b-PTE) nanoparticles and insulin loaded p(AAPBA-b-PTE) nanoparticles were prepared. The properties of pH, temperature and glucose sensitivity were investigated. And tested the drug loading and release of NPs. The nanoparticle toxicity was observed through cell and animal experiments, and the nanoparticle biodegradation process under physiological conditions was also observed. Finally, the effects of NPs on reducing blood sugar, antioxidation and improving micro inflammation were investigated in vivo.
Results: Based on PTE, we successfully synthesized p(AAPBA-b-PTE) NPs. The NPs were basically round in shape with sizes between 150 and 250 nm. It has good pH and glucose sensitivity. The entrapment efficiency (EE) of insulin loaded NPs is about 56%, and the drug loading (LC) is about 13%. The highest release of insulin was 70%, and the highest release of PTE was 85%. Meanwhile, the insulin could undergo self-regulation according to the change of glucose concentration, thus achieving an effective and sustained release. Both in vivo and in vitro experiments showed that the NPs were safe and nontoxic. Under physiological conditions, it can be completely degraded within 40 days. Fourteen days after the mice were injected with p(AAPBA-b-PTE) NPs, there were no obvious abnormalities in the heart, liver, spleen, lung, and kidney. Moreover, the NPs can effectively reduce blood glucose, improve the antioxidant capacity and improve the micro inflammation status in mice.
Conclusions: Using PTE as raw material, p(AAPBA-b-PTE) NPs were successfully prepared, which can effectively reduce blood glucose, improve antioxidant capacity, and reduce inflammatory response. It provided a new way for the combination of plant extracts and biomaterials to regulate and treat diseases through NPs or other dosage forms.
Keywords
Pterostilbene (PTE), 3-acrylamidophenylboronic acid (AAPBA), NPs (NPs), Glucose sensitivity, Drug carrier, Insulin delivery
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Scheme01.png
Scheme 1. Synthesis process of p(AAPBA-b-PTE) and p(AAPBA-b-PTE) NPs loaded with insulin
- Scheme02.png
Scheme 2. Synthesis of molecular structure of acrylic acid-PTE(A), p(AAPBA) (B) and p(AAPBA-b-PTE) (C).
- AdditionalInformation.docx
Additional file 1: Figure.S1 Nanoparticle swelling images under TEM after 1(A), 4(B), 10(C), 40(D)days. Figure.S2 CD spectra of the insulin released from NPs and standard insulin in PBS at pH 7.4, 25 °C. Table S1. The Mw and Mn and PDI of the p(AAPBA-b-PTE). Table S2. Ritger-Peppas results of p(AAPBA-b-PTE)2 NPs.
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CURRENT STATUS: Under Review
Version 1
Posted 20 Apr, 2021
No community comments so far
Editorial decision: Major revision
On 08 May, 2021
Review #2 received
Received 06 May, 2021
Reviewer #2 agreed
On 25 Apr, 2021
Review #1 received
Received 22 Apr, 2021
Reviews received
Received 21 Apr, 2021
Reviewers invited
Invitations sent on 21 Apr, 2021
Reviewer #1 agreed
On 20 Apr, 2021
Editor assigned
On 19 Apr, 2021
Editor invited
On 18 Apr, 2021
Submission checks complete
On 17 Apr, 2021
First submitted
On 16 Apr, 2021
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Subject Areas
Nanoscience
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This preprint is under consideration at Journal of Nanobiotechnology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 20 Apr, 2021
No community comments so far
Editorial decision: Major revision
On 08 May, 2021
Review #2 received
Received 06 May, 2021
Reviewer #2 agreed
On 25 Apr, 2021
Review #1 received
Received 22 Apr, 2021
Reviews received
Received 21 Apr, 2021
Reviewers invited
Invitations sent on 21 Apr, 2021
Reviewer #1 agreed
On 20 Apr, 2021
Editor assigned
On 19 Apr, 2021
Editor invited
On 18 Apr, 2021
Submission checks complete
On 17 Apr, 2021
First submitted
On 16 Apr, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nanoscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Aim: New envisions are put forward on the cross application of plant extracts and biomaterials, especially new conjectures are put forward on glucose lowering nanodrug delivery systems.
Study design and methods: In this study, pterostilbene (PTE) was esterified with acryloyl chloride firstly, and then 3-acrylamidophenyl boric acid (AAPBA) and PTE esterified by acryloyl chloride were copolymerized into p(AAPBA-b-PTE). The characterization and structure of its polymer were examined. Additionally, p(AAPBA-b-PTE) nanoparticles and insulin loaded p(AAPBA-b-PTE) nanoparticles were prepared. The properties of pH, temperature and glucose sensitivity were investigated. And tested the drug loading and release of NPs. The nanoparticle toxicity was observed through cell and animal experiments, and the nanoparticle biodegradation process under physiological conditions was also observed. Finally, the effects of NPs on reducing blood sugar, antioxidation and improving micro inflammation were investigated in vivo.
Results: Based on PTE, we successfully synthesized p(AAPBA-b-PTE) NPs. The NPs were basically round in shape with sizes between 150 and 250 nm. It has good pH and glucose sensitivity. The entrapment efficiency (EE) of insulin loaded NPs is about 56%, and the drug loading (LC) is about 13%. The highest release of insulin was 70%, and the highest release of PTE was 85%. Meanwhile, the insulin could undergo self-regulation according to the change of glucose concentration, thus achieving an effective and sustained release. Both in vivo and in vitro experiments showed that the NPs were safe and nontoxic. Under physiological conditions, it can be completely degraded within 40 days. Fourteen days after the mice were injected with p(AAPBA-b-PTE) NPs, there were no obvious abnormalities in the heart, liver, spleen, lung, and kidney. Moreover, the NPs can effectively reduce blood glucose, improve the antioxidant capacity and improve the micro inflammation status in mice.
Conclusions: Using PTE as raw material, p(AAPBA-b-PTE) NPs were successfully prepared, which can effectively reduce blood glucose, improve antioxidant capacity, and reduce inflammatory response. It provided a new way for the combination of plant extracts and biomaterials to regulate and treat diseases through NPs or other dosage forms.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Scheme01.png
Scheme 1. Synthesis process of p(AAPBA-b-PTE) and p(AAPBA-b-PTE) NPs loaded with insulin
- Scheme02.png
Scheme 2. Synthesis of molecular structure of acrylic acid-PTE(A), p(AAPBA) (B) and p(AAPBA-b-PTE) (C).
- AdditionalInformation.docx
Additional file 1: Figure.S1 Nanoparticle swelling images under TEM after 1(A), 4(B), 10(C), 40(D)days. Figure.S2 CD spectra of the insulin released from NPs and standard insulin in PBS at pH 7.4, 25 °C. Table S1. The Mw and Mn and PDI of the p(AAPBA-b-PTE). Table S2. Ritger-Peppas results of p(AAPBA-b-PTE)2 NPs.
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