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Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.

ABSTRACT: Type 1 diabetes mellitus (T1DM) has been defined as an autoimmune disease characterised by immune-mediated destruction of the pancreatic β cells, leading to absolute insulin deficiency and hyperglycaemia. Current research has increasingly focused on immunotherapy based on immunosuppression and regulation to rescue T-cell-mediated β-cell destruction. Although T1DM immunotherapeutic drugs are constantly under clinical and preclinical development, several key challenges remain, including low response rates and difficulty in maintaining therapeutic effects. Advanced drug delivery strategies can effectively harness immunotherapies and improve their potency while reducing their adverse effects. In this review, we briefly introduce the mechanisms of T1DM immunotherapy and focus on the current research status of the integration of the delivery techniques in T1DM immunotherapy. Furthermore, we critically analyse the challenges and future directions of T1DM immunotherapy.

SUBMITTER: Huang M

PROVIDER: S-EPMC10182560 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.

Huang Mingshu M Chen Weixing W Wang Min M Huang Yisheng Y Liu Hongyu H Ming Yue Y Chen Yuanxin Y Tang Zhengming Z Jia Bo B

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20230513 3

Type 1 diabetes mellitus (T1DM) has been defined as an autoimmune disease characterised by immune-mediated destruction of the pancreatic β cells, leading to absolute insulin deficiency and hyperglycaemia. Current research has increasingly focused on immunotherapy based on immunosuppression and regulation to rescue T-cell-mediated β-cell destruction. Although T1DM immunotherapeutic drugs are constantly under clinical and preclinical development, several key challenges remain, including low respon ...[more]

PMID: 37178431

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Project description:Diabetes mellitus (DM) is a chronic progressive metabolic disease that involves uncontrolled elevation of blood glucose levels. Among various therapeutic approaches, GLP-1 prevents type 2 diabetes mellitus (T2DM) patients from experiencing hyperglycemic episodes. However, the short half-life (<?5 min) and rapid clearance of GLP-1 often limits its therapeutic use. Here, we developed an oral GLP-1 gene delivery system to achieve an extended antidiabetic effect.Human IgG1 (hIgG1)-Fc-Arg/pDNA complexes were prepared by an electrostatic complexation of the expression plasmid with various ratios of the positively modified Fc fragments of an antibody (hIgG1-Fc-Arg) having a targeting ability to FcRn receptor. The shape and size of the complexes were examined by atomic force and field emission electron microscope. The stability of the complexes was tested in simulated gastrointestinal pH and physiological serum condition. Cellular uptake, transport, and toxicity of the complexes were tested in the Caco-2 cells. Biodistribution and antidiabetic effect of the complexes were observed in either Balb/c mice or Lepdb/db mice.A 50/1 ratio of the hIgG1-Fc-Arg/pDNA produced a complex structure having approximately 40 ~?60 nm size and also demonstrated protection of pDNA in the complex from the physiological pH and serum conditions. Cellular uptake and transport of the complex were demonstrated in Caco-2 cells having FcRn receptor expression and forming the monolayer-polarized structure. The cellular toxicity of both delivery vehicle and the complex revealed their minimal toxicity comparable with nontoxicity of a commercial transfection reagent. Biodistribution of the complex showed the detectable distribution of the complex in the most parts of gastrointestinal tract due to ubiquitous expression of the FcRn receptors. An in vivo type 2 diabetes treatment study of oral administration of hIgG1-Fc-9Arg/pGLP-1 complexes showed absorption and expression in GI tract of either Balb/c mice or Lepdb/db mice.In this study, we developed an oral GLP-1 gene delivery system on the platform of cationic hIgG1-Fc-9Arg. Prolonged t1/2, less immunoactivity, and better bioactivities of hIgG-Fc-9Arg/pGLP-1 complexes appeared to be a promising approach to achieve potent treatment of type 2 diabetes treatment.

Project description:BackgroundThere is limited evidence on whether screening for type 2 diabetes mellitus affects health outcomes. A recent systematic review of randomised clinical trials found only one trial that met their inclusion criteria; therefore, current guidelines for screening interventions for type 2 diabetes mellitus are based on expert opinions and best practice rather than synthesised evidence. This systematic review seeks to collate evidence from non-randomised studies to investigate the effect of screening for adults with type 2 diabetes on outcomes including diabetes-related morbidity, mortality (all-cause and diabetes-related) and harms.MethodsThis systematic review will follow Effective Practice and Organisation of Care (EPOC) guidelines for the synthesis of non-randomised studies. We will search PubMed/MEDLINE, Scopus, Web of Science, CINAHL, Academic Search Premier and Health Source Nursing Academic (from inception onwards). We will include non-randomised trials, controlled before-after studies, interrupted time-series studies, repeated measures studies and concurrently controlled prospective cohort studies. The primary outcome will be diabetes-related morbidity (microvascular complications of diabetic retinopathy, nephropathy or neuropathy or macrovascular complications of non-fatal myocardial infarction, peripheral arterial disease or non-fatal stroke). The secondary outcomes will be mortality (all-cause and diabetes-related) and harms of screening strategies to patients (including psychological harms or adverse events following treatments) or to health care system (including resource allocation for false-positives or overdiagnosis). Two reviewers will independently screen all citations and full-text articles. Data will be abstracted by one reviewer and checked by a second. The risk of bias of individual studies will be appraised using the ROBINS-I tool. GRADE will be used to determine the quality of the scientific evidence. If feasible, we will conduct random effects meta-analysis where appropriate. If necessary, analyses will be conducted to explore the potential sources of heterogeneity (e.g. age, sex, socio-economic status, rural versus urban or low-middle income versus high-income country). We will disseminate the findings via publications and through relevant networks.DiscussionThe protocol outlines the methods for systematically reviewing and synthesising evidence of screening strategies for type 2 diabetes mellitus and their effect on health outcomes associated with the disease. The potential impact of this systematic review is improved evidence-informed decision-making for policies and practice for screening of type-2 diabetes.Systematic review registrationPROSPERO CRD42020147439.

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Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.

Publications

Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.

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