An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics
Curcumin exhibits compromised bioavailability upon oral administration due to its inherent limitations, including low aqueous solubility, poor membrane permeability, and chemical instability. Inspired by the efficient mechanism by which viruses penetrate mucus and cells, we constructed an electrical...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/12/2536 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839653234456657920 |
|---|---|
| author | Qiuxu An Yuanyuan Liu Guodong Liang Yuewu Wang Fengying Liang Yunyang Bai Chaolu Eerdun Riqing Cheng Haifeng Zhang Xiaojie Lv |
| author_facet | Qiuxu An Yuanyuan Liu Guodong Liang Yuewu Wang Fengying Liang Yunyang Bai Chaolu Eerdun Riqing Cheng Haifeng Zhang Xiaojie Lv |
| author_sort | Qiuxu An |
| collection | DOAJ |
| description | Curcumin exhibits compromised bioavailability upon oral administration due to its inherent limitations, including low aqueous solubility, poor membrane permeability, and chemical instability. Inspired by the efficient mechanism by which viruses penetrate mucus and cells, we constructed an electrically neutral and hydrophilic nanocarrier (C60-CPP5/Pser@CUR) using fullerene C60 as the matrix modified with cell-penetrating peptides and phosphoserine. CPP5 facilitates efficient cellular internalization of therapeutic agents, while the incorporation of phosphoserine serves as a charge reversal strategy. This design enables dynamic surface charge modulation to enhance curcumin’s trans-barrier delivery efficiency. Systematic in vitro and in vivo evaluations demonstrated that the synthesized carrier significantly improved the synergistic effects of mucus penetration and cellular uptake. The Caco-2 cellular uptake of curcumin-loaded carriers was 2.26 times higher than that of free drugs. In a single-pass intestinal perfusion study in rat models, this nanocarrier significantly enhanced the absorption of curcumin in the duodenal and colonic regions. In the in vivo experiments, compared with free curcumin, its C<sub>max</sub> and AUC<sub>0–t</sub> achieved improvements of 2.60 times and 14.70 times, respectively. This virus-mimetic platform dynamically adapts to micro-environmental demands through charge reversal mechanisms, effectively overcoming sequential biological barriers and providing a robust strategy for oral delivery of hydrophobic therapeutics. |
| format | Article |
| id | doaj-art-4f3b3b43b17a43c89d3f4d9cdc80adcf |
| institution | Matheson Library |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-4f3b3b43b17a43c89d3f4d9cdc80adcf2025-06-25T14:13:29ZengMDPI AGMolecules1420-30492025-06-013012253610.3390/molecules30122536An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption CharacteristicsQiuxu An0Yuanyuan Liu1Guodong Liang2Yuewu Wang3Fengying Liang4Yunyang Bai5Chaolu Eerdun6Riqing Cheng7Haifeng Zhang8Xiaojie Lv9College of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Basic Medicine, Inner Mongolia Medical University, Hohhot 010110, ChinaCollege of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, ChinaCurcumin exhibits compromised bioavailability upon oral administration due to its inherent limitations, including low aqueous solubility, poor membrane permeability, and chemical instability. Inspired by the efficient mechanism by which viruses penetrate mucus and cells, we constructed an electrically neutral and hydrophilic nanocarrier (C60-CPP5/Pser@CUR) using fullerene C60 as the matrix modified with cell-penetrating peptides and phosphoserine. CPP5 facilitates efficient cellular internalization of therapeutic agents, while the incorporation of phosphoserine serves as a charge reversal strategy. This design enables dynamic surface charge modulation to enhance curcumin’s trans-barrier delivery efficiency. Systematic in vitro and in vivo evaluations demonstrated that the synthesized carrier significantly improved the synergistic effects of mucus penetration and cellular uptake. The Caco-2 cellular uptake of curcumin-loaded carriers was 2.26 times higher than that of free drugs. In a single-pass intestinal perfusion study in rat models, this nanocarrier significantly enhanced the absorption of curcumin in the duodenal and colonic regions. In the in vivo experiments, compared with free curcumin, its C<sub>max</sub> and AUC<sub>0–t</sub> achieved improvements of 2.60 times and 14.70 times, respectively. This virus-mimetic platform dynamically adapts to micro-environmental demands through charge reversal mechanisms, effectively overcoming sequential biological barriers and providing a robust strategy for oral delivery of hydrophobic therapeutics.https://www.mdpi.com/1420-3049/30/12/2536fullereneintestinal absorption barriernanocarriercharge reversalcell-penetrating peptides |
| spellingShingle | Qiuxu An Yuanyuan Liu Guodong Liang Yuewu Wang Fengying Liang Yunyang Bai Chaolu Eerdun Riqing Cheng Haifeng Zhang Xiaojie Lv An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics Molecules fullerene intestinal absorption barrier nanocarrier charge reversal cell-penetrating peptides |
| title | An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics |
| title_full | An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics |
| title_fullStr | An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics |
| title_full_unstemmed | An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics |
| title_short | An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics |
| title_sort | effective oral nanodelivery material for curcumin ingenious utilization of gastrointestinal absorption characteristics |
| topic | fullerene intestinal absorption barrier nanocarrier charge reversal cell-penetrating peptides |
| url | https://www.mdpi.com/1420-3049/30/12/2536 |
| work_keys_str_mv | AT qiuxuan aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT yuanyuanliu aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT guodongliang aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT yuewuwang aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT fengyingliang aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT yunyangbai aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT chaolueerdun aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT riqingcheng aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT haifengzhang aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT xiaojielv aneffectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT qiuxuan effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT yuanyuanliu effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT guodongliang effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT yuewuwang effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT fengyingliang effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT yunyangbai effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT chaolueerdun effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT riqingcheng effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT haifengzhang effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics AT xiaojielv effectiveoralnanodeliverymaterialforcurcuminingeniousutilizationofgastrointestinalabsorptioncharacteristics |