In situ hybrid nano drug delivery system (IHN-DDS) of antiretroviral drug for simultaneous targeting to multiple viral reservoirs: An in vivo proof of concept

Background: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in glucose homeostasis and food intake. In people, GLP-1 receptor agonists (GLP-1RAs) are commonly used for the treatment of type 2 diabetes mellitus (DM) and obesity; however, non-adherence to injectable medications is common. OKV-119 is an investigational drug delivery system intended for subdermal implantation and delivery of the GLP-1RA exenatide for up to 6 months.Hypothesis/Objectives: Develop protocols for the subcutaneous (SC) insertion and removal of OKV-119 and to evaluate its tolerability, in vivo drug-releasing characteristics, and weight-loss effects in cats.Animals: Two cadaveric and 19 purpose-bred cats.Methods: In cadavers, OKV-119 insertion protocol and imaging were performed at three SC locations. The safety and tolerability of OKV-119 implants were assessed in a small (n = 4 cats) 62-day study. Weekly plasma exenatide concentrations and body weight were measured in a 42-day proof-of-concept study designed to evaluate OKV-119 prototypes implanted in cats (n = 15).Results: In anesthetized cats, the duration of insertion and removal procedures was 1–2 min. OKV-119 was easily identified on radiographs, and well-tolerated without any apparent implant site reactions. Following implantation, exanatide plasma concentrations were observed for up to 35 days. Plasma exenatide concentrations were correlated to weight loss.Conclusion and clinical importance: Our findings suggest that OKV-119 could be easily inserted and removed during a routine clinic visit and can be used to safely and effectively deliver exenatide. Future studies of OKV-119, configured to release exenatide for a longer extended months-long duration, are warranted to determine whether the combination of metabolic improvements and beneficial weight-loss, coupled with minimal impact on pet-owner's lifestyle, lead to improved outcomes for obese cats and feline DM patients.

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Construction of Intelligent Nano-Drug Delivery System for Targeting Extranodal Nasal Natural Killer/Thymus Dependent Lymphocyte

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3048 ◽

2021 ◽

Vol 17 (3) ◽

pp. 487-500

Author(s):

Xinyu Zhang ◽

Jun Wu ◽

Dongjun Lin

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Carrier ◽

Reticuloendothelial System ◽

Treatment Programs ◽

Multi Drug Resistance ◽

Nano Drug Delivery ◽

Further Development

Extranodal nasal NK/T-cell lymphoma is highly aggressive and malignant. Owing to the lack of multi-center prospective controlled studies, there is not a unified standard for the current clinical best treatment model. In recent years, new nano-drug delivery systems have made great progress in the field of tumor treatment. However, research on ENKTL is still in its infancy. The authors' previous research has proven that the dextran nano-drug delivery system can optimize and improve the in vivo pharmacokinetic behavior and anti-tumor effects of doxorubicin through interaction with the reticuloendothelial system and the complex tumor microenvironment. At the same time, gemcitabine, which is commonly used in the clinical treatment of ENKTL, and cisplatin, which is a radiosensitizer, both contain free amino groups, which can be successfully grafted to aldehyde-based natural polysaccharides. Therefore, based on the natural nano-drug carrier, we constructed a smart long-circulation drug delivery system that co-loaded gemcitabine and cisplatin and targeted ENKTL to achieve effective treatment of ENKTL under the dual treatment mode of chemotherapy and radiosensitization. This project improves the radiosensitivity of ENKTL and overcomes the multi-drug resistance of chemotherapeutics through the radiotherapy-cooperative natural nano-drug delivery system and provides a new idea for the further development and optimization of ENKTL treatment programs.

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Construction of a tumor microenvironment pH-responsive cleavable PEGylated hyaluronic acid nano-drug delivery system for colorectal cancer treatment

Biomaterials Science ◽

10.1039/c9bm01927h ◽

2020 ◽

Vol 8 (7) ◽

pp. 1885-1896 ◽

Cited By ~ 16

Author(s):

Xinyu Zhang ◽

Minyi Zhao ◽

Nan Cao ◽

Wei Qin ◽

Meng Zhao ◽

...

Keyword(s):

Drug Delivery ◽

Hyaluronic Acid ◽

Drug Delivery System ◽

Delivery System ◽

Ph Responsive ◽

Nano Drug Delivery ◽

Imine Bond ◽

Microenvironment Ph ◽

Colorectal Cancer Treatment

To improve the tumor cell active targeting, uptake efficiency and circulation time of doxorubicin (DOX) in vivo. Herein, we constructed a cleavable PEGylated hyaluronic acid nano-drug delivery system (HA–mPEG2k–DOX) based on pH-responsive imine bond.

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