Pectin-based double network hydrogels as local depots of celastrol for enhanced antitumor therapy.

In this study, A double-network (DN) hydrogel composed of a physical glycyrrhizic acid (GA) network and a chemically crosslinked pectin-based network was fabricated as a local depot of celastrol (CEL) for cancer treatment. The obtained DN hydrogel possessed excellent mechanical performance, flexibility, biocompatibility, biodegradability and self-healing property. Furthermore, the release profile of CEL loaded DN hydrogel maintained a controlled and sustained release of CEL for a prolonged period. Finally, in vivo animal experiments demonstrated that the DN hydrogel could significantly enhance the therapeutic efficiency of CEL in CT-26 tumor-bearing mice upon intratumoral injection while effectively alleviate the toxicity of the CEL. In summary, this injectable pectin-based double network hydrogels are ideal delivery vehicle for tumor therapy.

Pectin based hydrogel with covalent coupled doxorubicin and limonin loading for lung tumor therapy.

Self-healing hydrogels have shown great application potential in drug delivery for anti-tumor therapy and tissue engineering. In this research, Doxorubicin (DOX) was coupled onto the oxidized pectin (pec-Ald) to prepare DOX grafted pec-AD and used to fabricate self-healing hydrogel for lung cancer therapy combined with novel herbal medicine extract limonin targeting lung cancer cells. The hydrogel was prepared with P(NIPAM195-co-AH54) cross-linking and the hydrazone bond cross-linked hydrogel showed good mechanical property and self-healing behavior. With pectin composition, the hydrogel was still biodegradable catalyzed by enzyme and in vivo. The hydrogel formed fast fit for injectable application and the hydrogel itself showed moderate lung cancer inhibition activity. With limonin loading, the hydrogel showed synergistic lung cancer therapy with the tumor growth greatly inhibited. The covalent coupling of DOX and loaded limonin in the hydrogel decreased in vivo toxicity and the hydrogel degraded on time. With biodegradability and improved lung cancer therapy efficiency, this DOX grafted self-healing hydrogel could find great potential application in cancer therapy in near future.

Mussel-inspired self-healing hydrogel form pectin and cellulose for hemostasis and diabetic wound repairing.

Diabetic wound is considered as a kind of chronic wound prone to infection and difficult to repair due to high glucose level in the blood of patients. In this research, a biodegradable self-healing hydrogel with mussel inspired bioadhesion and anti-oxidation properties is fabricated based on Schiff-base cross-linking. The hydrogel was designed from dopamine coupled pectin hydrazide (Pec-DH) and oxidized carboxymethyl cellulose (DCMC) for mEGF loading as a diabetic wound repair dressing. The Pectin and CMC as natural feedstock endowed the hydrogel with biodegradability to avoid possible side effects, while the coupled catechol structure could enhance the tissue adhesion of the hydrogel for hemostasis. The results showed the Pec-DH/DCMC hydrogel formed fast and can cover irregular wounds with good sealing effect. The catechol structure also improved the reactive oxygen species (ROS) scavenging ability of the hydrogel, which can eliminate the negative effect of ROS during wound healing. The in vivo diabetic wound healing experiment revealed the hydrogel as mEGF loading vehicle greatly enhanced the diabetic wound repairing rate in mice model. As a result, the Pec-DH/DCMC hydrogel could show advantages as EGF carrier in wound healing applications.

Biodegradable hydrogel from pectin and carboxymethyl cellulose with Silibinin loading for lung tumor therapy.

Serious side effects of chemotherapy drugs greatly limited the anticancer performance, while targeted drug delivery could improve the therapeutic effect and reduce side effects. In this work, biodegradable hydrogel was fabricated from pectin hydrazide (pec-H) and oxidized carboxymethyl cellulose (DCMC) for localized Silibinin delivery in lung adenocarcinoma treatment. The self-healing pec-H/DCMC hydrogel showed blood compatibility and cell compatibility both in vitro and in vivo, and could be degraded by enzymes. The hydrogel also formed fast fit for injectable applications and showed sustained drug release characteristic sensitive to pH based on acylhydrzone bond cross-linked networks. The Silibinin, as a specific lung cancer inhibiting drug targets TMEM16A ion channel, was loaded into the pec-H/DCMC hydrogel to treat the lung cancer in mice model. The results showed that the hydrogel loaded Silibinin significantly enhanced the anti-tumor efficiency in vivo and greatly reduced the toxicity of the Silibinin. Based on the dual effect of improving efficacy and reducing side effects, the pec-H/DCMC hydrogel with Silibinin loading have broad application prospects to inhibit lung tumor growth in clinic.

Self-healing pectin/cellulose hydrogel loaded with limonin as TMEM16A inhibitor for lung adenocarcinoma treatment.

Lung cancer as one of the highest incident malignant tumors did not receive satisfactory chemotherapy due to lack of specific drug targets and targeted drugs. This study screened a new effective lung tumor inhibitor limonin from herbal medicine, which inhibited proliferation and promoted apoptosis of lung adenocarcinoma cells by targeting specific high expressed TMEM16A ion channel. Moreover, a novel biodegradable self-healing hydrogel was prepared from acylhydrazide functionalized carboxymethyl cellulose (CMC-AH) and oxidized pectin (pec-CHO) to reduce the side effects of the limonin to the body. The hydrogels showed fast gelation, good biocompatibility and sustained limonin release property. The limonin-loaded hydrogel significantly inhibited the growth of lung adenocarcinoma in xenografts mice because the limonin inhibited the proliferation, migration and promoted apoptosis of LA795 cells, and eliminated the acute toxicity through sustained release from the hydrogel. Combined the antitumor performance of the limonin and sustained release of pec-CHO/CMC-AH hydrogel, this limonin/hydrogel system achieved satisfactory antitumor effect and eliminated side effects in vivo. Therefore, this system has great potential application for enhanced lung adenocarcinoma therapy.

Self-healing hydrogel based on polyphosphate-conjugated pectin with hemostatic property for wound healing applications.

Self-healing hydrogels have important application in hemostasis and wound repairing. In this research, pectin based self-healing hydrogel was fabricated with conjugated polyphosphate for hemostatic and wound healing applications. The hydrogel formed without any stimulus and hydrogel kept its biocompatibility; at the same time, the hydrogel degraded completely by enzyme and in vivo. The polyphosphate conjugated hydrogel also showed self-healing property and sustained release performance with strong coagulation characteristic. More importantly, the in vivo experiment revealed that the polyphosphate conjugated hydrogel reduced the blood loss and hemostasis time in hemorrhage model; meanwhile, the hydrogel accelerated the wound repairing rate of the open wound by preventing bacterial invasion. Altogether, the PolyP conjugated hemostatic pectin-based hydrogel is a good candidate as wound dressing material applied in clinic or open wound repairing.

Pectin-based injectable and biodegradable self-healing hydrogels for enhanced synergistic anticancer therapy.

We report a new injectable and biodegradable self-healing hydrogel that shows enhanced anticancer drug release property. The hydrogel was prepared based on biodegradable pectin aldehyde (pectin-CHO) and acylhydrazide functionalized polymer poly(N-isopropylacrylamide-stat-acylhydrazide) P(NIPAM-stat-AH). Due to the dynamic nature of acylhydrazone bonds, the hydrogel exhibits self-healing behavior and its mechanical properties can be regulated by the weight ratio of P(NIPAM-stat-AH) to pectin-CHO. The in vitro and in vivo experiments show the hydrogel has not only good biocompatibility and biodegradability, but also decreases the toxicity of the drugs to living body and exhibits controlled drug release behavior as synergetic anti-tumor drug delivery carriers. The results demonstrate that the pectin-based self-healing hydrogels are injectable, biodegradable, and self-healable that is promising for localized anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Injectable hydrogels with self-healing property and biodegradability are excellent candidates as drug loading and release carrier for biomedical applications. However the pectin as a biobased material is always neglected in self-healing hydrogel preparation. In this study, we fabricated biodegradable self-healing hydrogels from aldehyde group bearing pectin (pectin-CHO) and thermo-responsive copolymer of P(NIPAM-stat-AH). The hydrogel showed sustained drug release behavior, good biocompatibility and biodegradability both in vitro and in vivo. The in vivo experiment shows that the hydrogel with coloaded DOX and CA4 has synergetic therapy to CT26 tumors and this kind of biodegradable hydrogel has great potential application in antitumor therapy.