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PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY · 2022 · IF 3.915

Microemulsion-thermosensitive gel composites as in situ-forming drug reservoir for periodontitis tissue repair through alveolar bone and collagen regeneration strategy

Yang Ding,Yuxiao Wang,Jiaxin Li,Maomao Tang,Hairong Chen,Guichun Wang,Jian Guo,Shuangying Gui

A satisfactory clinical effect in treating periodontitis is often difficult to achieve by conventional non-surgical systemic drug delivery due to the narrow anatomical structure of the periodontal pocket and insufficient drug concentration at lesion sites. In addition, the feasibility of combating periodontal tissue lesions by restoring the alveolar bone and allowing collagen regeneration has not been fully explored. The objective of this study was to prepare a microemulsion integrating the anti-inflammatory and osteogenic active ingredients of baicalin and clove oil (BC-MEs). Then, the composite hydrogel obtained by mixing poloxamer 407 and 188 was used as the thermosensitive gel matrix to load BC-MEs and form a drug reservoir (Gel-BC-MEs) injectable in situ. Gel-BC-MEs exhibited a significant, sustained release of baicalin for 12 h, gelation temperature was 33.4 ± 0.36 °C, and pH was 5.45 ± 0.12. The experiment on a rat periodontitis model demonstrated that Gel-BC-MEs significantly improved periodontal tissue repair by collagen regeneration and osteogenesis by inhibiting osteoclast infiltration. This study proposes a novel strategy for periodontal tissue repair by enhancing the therapeutic potential of a microemulsion using an in situ nano-gel delivery system.

CAS / MDL: 9005-64-5 25322-68-3
研究领域: 药剂学 · 牙科材料 · 组织工程 · 药物递送系统
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Nature Biomedical Engineering · 2024 · IF 26.8

In situ formation of biomolecular condensates as intracellular drug reservoirs for augmenting chemotherapy

Liang Tingxizi,Dong Yuxiang,Cheng Irina,Wen Ping,Li Fengqin,Liu Feng,Wu Qing,Ren En,Liu Peifeng,Li Hongjun,Gu Zhen

Biomolecular condensates, which arise from liquid–liquid phase separation within cells, may provide a means of enriching and prolonging the retention of small-molecule drugs within cells. Here we report a method for the controlled in situ formation of biomolecular condensates as reservoirs for the enrichment and retention of chemotherapeutics in cancer cells, and show that the approach can be leveraged to enhance antitumour efficacies in mice with drug-resistant tumours. The method involves histones as positively charged proteins and doxorubicin-intercalated DNA strands bioorthogonally linked via a click-to-release reaction between trans -cyclooctene and tetrazine groups. The reaction temporarily impaired the phase separation of histones in vitro, favoured the initiation of liquid–liquid phase separation within cells and led to the formation of biomolecular condensates that were sufficiently large to be retained within tumour cells. The controlled formation of biomolecular condensates as drug reservoirs within cells may offer new options for boosting the efficacies of cancer therapies.

研究领域: 药理学 · 癌症研究 · 细胞生物学 · 分子生物学
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Acta Biomaterialia · 2025 · IF 9.6

A drug reservoir strategy for long-acting cancer therapy using morphologically transformed amphiphilic polymeric nanoparticles

Jiao Sun,Yiqing Wang,Jiaxing Zhang,Jianhao Wang,Cheng Wang

The effective accumulation of drugs within tumor tissues is impeded by extracellular barriers, necessitating repeated dosing in cancer therapy. However, repeated dosing can trigger the accelerated blood clearance (ABC) effect, resulting in limited therapeutic efficacy. Herein, in this study, a drug reservoir strategy was proposed to solve this dilemma, using an amphiphilic polymer (LPHF) with tunable hydrophilicity and morphology transformation capabilities. At pH 7.4, LPHF with balanced hydrophilicity can self-assemble into nanoparticles and be loaded with Dox (LPHF@Dox). At pH 6.5, LPHF@Dox with reduced hydrophilicity undergoes an immediate transition from a dispersed state to a deposited state, which can serve as a tumor-specific drug reservoir. Under the weakly acidic tumor microenvironment, the amide with adjacent carboxylic acid groups in LPHF exhibits pH-dependent hydrolysis, leading to a reversion of LPHF to a hydrophilic state and reconstitution into nanoparticles (LPHF@Dox RC ). The resulting LPHF@Dox RC undergoes charge reversal to a positive state, which coordinated with conjugated folic acid, to synergistically improves both the cellular internalization and tumor penetration of LPHF@Dox RC . This intelligent amphiphilic polymer, functioning as a tumor-specific drug reservoir, may provide a new approach for effective cancer treatment. Statement of significance This study introduces a pH-responsive polymeric nanoparticle (LPHF) that transforms into a tumor-specific drug reservoir under acidic conditions, addressing the challenge of repeated dosing in cancer therapy. Unlike conventional systems, LPHF deposits directly in tumors via pH-triggered hydrophobicity changes. As the tumor microenvironment hydrolyzes LPHF, it releases reconstituted nanoparticles with positive charges, enhancing cellular uptake and deep tumor penetration. This dual-phase strategy—localized drug retention followed by controlled release—significantly reduces side effects and improves therapeutic efficacy. By combining material innovation with biological insights, this work offers a promising approach for long-acting cancer treatment, potentially minimizing dosing frequency. Its interdisciplinary design bridges chemistry and biomedicine, appealing to researchers and students interested in smart drug delivery and sustainable healthcare solutions.

研究领域: 纳米医学 · 高分子科学 · 癌症治疗 · 药物递送系统 · 生物材料 · 药学 · 生物化学 · 材料科学
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Colloid and Interface Science Communications · 2023 · IF 4.5

In situ forming mesoporous polydopamine nanocomposite thermogel for combined chemo-photothermal therapy of intraocular cancer

Chunwen Tao,Yate Huang,Junrong Chen,Qiaohua Peng,Kaihui Nan,Yangjun Chen

Intraocular cancers such as retinoblastoma and uveal melanoma will induce severe vision loss or even death. Herein, a versatile nanocomposite thermogel based on hexanoyl glycol chitosan (HGC) and mesoporous polydopamine nanoparticles (MPDA NPs) was designed for potential use as an intraocular “drug depot” for the treatment of intraocular tumors. The integrated HGC-MPDA thermogel showed reversible sol-gel transition property as well as injectable and in-situ gelation abilities. The incorporated MPDA NPs endowed the thermogel with outstanding NIR laser-based photothermal conversion ability and enabled NIR light-controlled drug release. Moreover, in vitro study revealed that drug-loaded thermogel ( [email protected] ) with the aid of 808 nm laser irradiation possessed superior anticancer effect than any single treatment via synergistic chemo-photothermal therapy. The present study demonstrated that HGC-MPDA could serve as a multifunctional platform for sustained and NIR light-responsive intravitreal drug delivery, avoiding repetitive injection, and the localized chemo-photothermal therapy provides a promising strategy against intraocular tumors.

CAS / MDL: 62-31-7 108-67-8
研究领域: 药学 · 肿瘤学 · 生物医学工程 · 材料科学
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