A high-efficiency, low-toxicity, phospholipids-based phase separation gel for long-term delivery of peptides

Zhang, Ting; Peng, Qiang; San, Feng-Ying; Luo, Jingwen; Wang, Mengxin; Wu, Wenqi; Gong, Tao; Zhang, Zhirong

doi:10.1016/j.biomaterials.2014.12.042

Cited by 47 publications

(36 citation statements)

References 30 publications

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“…The primary toxicity of the PPSG extracts could be caused by the small amount of ethanol in PPSG. However, upon exposed to body fluid in vivo, the PPSG implant extract could be diluted over time and the possible toxicity could be eliminated, which we demonstrated in a previous study [20]. In vitro release study of TP5-PPSG Fig.…”

Section: Resultsmentioning

confidence: 67%

“…The results also demonstrated the sustained and long-lasting pharmacokinetic behavior of TP5-PPSG, which would benefit the clinical use of TP5 by reducing the administration frequency and greatly improving patient compliance. In addition, we previously demonstrated that the inflammation response in rabbits caused by PPSG after a subcutaneous injection was low and acceptable, indicating the biocompatibility of the TP5 drug delivery system [20].…”

Section: Cytotoxicity Assay Of Ppsgmentioning

confidence: 96%

“…Preparation of PPSG and TP5-PPSG PPSG was prepared by a simple one-step stirring method according to our previous study [20]. In brief, E80, absolute ethanol and MCT in a weight ratio of 70:15:15 were mixed and agitated vigorously for two hours at room temperature.…”

Section: Cells and Animalsmentioning

confidence: 99%

“…Characterization of PPS Viscosity. The viscosity of PPSG after the phase transition was determined at room temperature with a method described in a previous study (DV-C, Brookfield Engineering Laboratories, Inc., USA) [20].…”

Section: Cells and Animalsmentioning

confidence: 99%

“…However, this system contained excessive water and a small amount of phospholipid to produce a low viscosity for injection, so its burst release could be relatively high and its pharmaceutical effect was of relatively short duration (i.e., a week). Recently, our group has developed a novel phospholipid-based phase separation gel (PPSG) that was a solvent-induced in situ forming gel and achieved a good longterm drug delivery property [20]. This gel formulation is based on high-content phospholipid, little anhydrous ethanol, and injection-grade oil, and it could be prepared easily by a onestep stirring method.…”

Section: Introductionmentioning

confidence: 99%

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Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies

et al. 2018

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Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition. Moreover, the PPSG exerted a low cytotoxicity in L929 cells and HUVECs, suggesting the biocompatibility of PPSG. A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo, revealing its sustained and controlled drug release property. Most importantly, in cyclophosphamide-induced immunosuppressive rats, a single dose of TP5 PPSG (15 mg/kg, sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio; such an immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (0.6 mg/kg per day, sc) for 14 consecutive days. Thus, TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple manufacture process, good biocompatibility and long-lasting immunomodulatory efficacy, which could greatly improve patient compliance.

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Section: Resultsmentioning

confidence: 67%

Section: Cytotoxicity Assay Of Ppsgmentioning

confidence: 96%

Section: Cells and Animalsmentioning

confidence: 99%

Section: Cells and Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies

et al. 2018

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Combination of Bacterial‐Photothermal Therapy with an Anti‐PD‐1 Peptide Depot for Enhanced Immunity against Advanced Cancer

Chen

Guo

Zhu

et al. 2019

Adv Funct Materials

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Photothermal therapy (PTT) is a promising cancer treatment, but it has so far proven successful only with relatively small subcutaneous tumors in animal models. Treating larger tumors (≈200 mm 3 ) is challenging because most PTT materials do not efficiently reach the hypoxic, avascular center of tumors, and the immunosuppressive tumor microenvironment prevents T cells from fighting against residual tumor cells, thereby allowing recurrence and metastasis. Here, the widely used PTT material polydopamine is coated on the surface of the facultative anaerobe Salmonella VNP20009, which can penetrate deep into larger tumors. The coated bacteria are intravenously injected followed by near-infrared laser irradiation at the tumor site, combined with a local inoculation of phospholipid-based phase separation gel containing the anti-programmed cell death-1 peptide AUNP-12. The gel releases AUNP-12 sustainably during 42 days, maintaining the tumor microenvironment as immunopermissive. Using a mouse model of melanoma, this triple combination of biotherapy, PTT, and sustainable programmed cell death-1 (PD-1) blockade shows high efficiency on eliciting robust antitumor immune responses and eliminating relatively large tumors in 50% of animals within 80 days. Thus, the results shed new light on a previously unrecognized immunological facet of bacteria-mediated therapy, and this innovative triple therapy may be a powerful cancer immunotherapy tool.

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In Situ Generated Medical Devices

Cohn

Sloutski

Elyashiv

et al. 2019

Adv Healthcare Materials

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Medical devices play a major role in all areas of modern medicine, largely contributing to the success of clinical procedures and to the health of patients worldwide. They span from simple commodity products such as gauzes and catheters, to highly advanced implants, e.g., heart valves and vascular grafts. In situ generated devices are an important family of devices that are formed at their site of clinical function that have distinct advantages. Among them, since they are formed within the body, they only require minimally invasive procedures, avoiding the pain and risks associated with open surgery. These devices also display enhanced conformability to local tissues and can reach sites that otherwise are inaccessible. This review aims at shedding light on the unique features of in situ generated devices and to underscore leading trends in the field, as they are reflected by key developments recently in the field over the last several years. Since the uniqueness of these devices stems from their in situ generation, the way they are formed is crucial. It is because of this fact that in this review, the medical devices are classified depending on whether their in situ generation entails chemical or physical phenomena.

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A high-efficiency, low-toxicity, phospholipids-based phase separation gel for long-term delivery of peptides

Cited by 47 publications

References 30 publications

Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies

Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies

Combination of Bacterial‐Photothermal Therapy with an Anti‐PD‐1 Peptide Depot for Enhanced Immunity against Advanced Cancer

In Situ Generated Medical Devices

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