Degradable polymeric vehicles for postoperative pain management

Brigham, Natasha; Ji, Ru-Rong; Becker, Matthew L.

doi:10.1038/s41467-021-21438-3

Cited by 38 publications

(27 citation statements)

References 150 publications

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“…[6,7] Local chemotherapy has received widespread attention for its ability to overcome limitations of the blood-brain barrier and maintain a longer effective drug dose at the tumor site while greatly reducing systemic toxicity. [8][9][10][11] Targeted drug delivery strategies based on intracranial implants, such as biodegradable polymer wafers, Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Surgery followed by chemotherapy and radiotherapy remains the standard treatment strategy for GBM patients.…”

Section: Introductionmentioning

confidence: 99%

“…Local chemotherapy has received widespread attention for its ability to overcome limitations of the blood‐brain barrier and maintain a longer effective drug dose at the tumor site while greatly reducing systemic toxicity. [ 8–11 ] Targeted drug delivery strategies based on intracranial implants, such as biodegradable polymer wafers, have been proposed to circumvent the blood‐brain barrier and deliver drugs appropriate to the patient's prognosis. [ 12–14 ] However, many challenges still remain, such as the deep penetration required for drugs to reach infiltrating tumor cells, the lack of multidrug delivery capacity with different release kinetics in a single device, occurrence of neurological disorders arising from mismatch between the rigid intracerebral implant and soft brain issues, and side effects caused by degradation products.…”

Section: Introductionmentioning

confidence: 99%

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Silk Microneedle Patch Capable of On‐Demand Multidrug Delivery to the Brain for Glioblastoma Treatment

et al. 2021

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Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Surgery followed by chemotherapy and radiotherapy remains the standard treatment strategy for GBM patients. However, challenges still exist when surgery is difficult or impossible to remove the tumor completely. Herein, the design, fabrication and application of a heterogenous silk fibroin microneedle (SMN) patch is reported for circumventing the blood‐brain barrier and releasing multiple drugs directly to the tumor site for drug combination treatment. The biocompatible and biodegradable SMN patch can dissolve slowly over time, allowing the sustained release of multiple drugs at different doses. Furthermore, it can be triggered remotely to induce rapid drug delivery at a designated stage after implantation. In the GBM mouse models, two clinically relevant chemotherapeutic agents (thrombin and temozolomide) and targeted drug (bevacizumab) are loaded into the SMN patch with individually controlled release profiles. The drugs are spatiotemporally and sequentially delivered for hemostasis, anti‐angiogenesis, and apoptosis of tumor cells. Device application is non‐toxic and results in decreased tumor volume and increased survival rate in mice. The SMN patch with on‐demand multidrug delivery has potential applications for the combined administration of therapeutic drugs for the clinical treatment of brain tumors when other methods are insufficient.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Silk Microneedle Patch Capable of On‐Demand Multidrug Delivery to the Brain for Glioblastoma Treatment

et al. 2021

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“…Biomaterials can be used to achieve controlled release of LA, which could lead to a safe, localized, long-acting postoperative pain treatment solution (Brigham et al., 2021 ). Nanocapsules, hydrogels, and nanoparticles are only a few of the biomaterial-based carriers that have been studied earlier.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management

Deng

Zhuang

et al. 2022

Drug Delivery

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Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 μm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity. HIGHLIGHTS Preparation and characterization of CS-GP/PC polymeric hydrogel system. BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution. Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells. Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.

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“…Common drugs widely used for postoperative analgesia include opioids, and nonopioids such as local anesthetics (LAs) and nonsteroidal anti-inflammatory drugs (NSAIDs) (Brigham et al., 2021 ). Due to opioid-related adverse events (respiratory depression, nausea, vomiting, etc.)…”

Section: Introductionmentioning

confidence: 99%

“…Current postoperative pharmacotherapy is typically achieved by injectable, transdermal, or subcutaneous routes (Brigham et al., 2021 ). Transdermal drug delivery system is an effective method for achieving localized drug delivery that can alleviate anxiety and discomfort caused by needle insertion, especially relive pain for up to 3 h or 3 months via self-administered by the patient (de Araújo et al., 2013 ; You et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Combination anesthetic therapy: co-delivery of ropivacaine and meloxicam using transcriptional transactivator peptide modified nanostructured lipid carriers in vitro and in vivo

Yuan

Feng

et al. 2022

Drug Delivery

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Combination therapy combining two drugs in one modified drug delivery system is used to achieve synergistic analgesic effect, and bring effective control of pain management, especially postoperative pain management. In the present study, a combination of drug delivery technologies was utilized. Transcriptional transactivator (TAT) peptide modified, transdermal nanocarriers were designed to co-deliver ropivacaine (RVC) and meloxicam (MLX) and anticipated to achieve longer analgesic effect and lower side effect. TAT modified nanostructured lipid carriers (TAT-NLCs) were used to co-deliver RVC and MLX. RVC and MLX co-loaded TAT-NLCs (TAT-NLCs-RVC/MLX) were evaluated through in vitro skin permeation and in vivo treatment studies. NLCs-RVC/MLX showed uniform and spherical morphology, with a size of 133.4 ± 4.6 nm and a zeta potential of 20.6 ± 1.8 mV. The results illustrated the anesthetic pain relief ability of the present constructed system was significantly improved by the TAT modification through the enhanced skin permeation efficiency and the co-delivery of MLX along with RVC that improved pain management by reducing inflammation at the injured area. This study provides an efficient and facile method for preparing TAT-NLCs-RVC/MLX as a promising system to achieve synergistic analgesic effect.

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Degradable polymeric vehicles for postoperative pain management

Cited by 38 publications

References 150 publications

Silk Microneedle Patch Capable of On‐Demand Multidrug Delivery to the Brain for Glioblastoma Treatment

Silk Microneedle Patch Capable of On‐Demand Multidrug Delivery to the Brain for Glioblastoma Treatment

Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management

Combination anesthetic therapy: co-delivery of ropivacaine and meloxicam using transcriptional transactivator peptide modified nanostructured lipid carriers in vitro and in vivo

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