Insulin Delivery Systems: Reducing Barriers to Insulin Therapy and Advancing Diabetes Mellitus Treatment

: Diabetes mellitus is found to be among the most suffered and lethal diseases for mankind. Diabetes mellitus type-1 is caused by the demolition of pancreatic islets responsible for the secretion of insulin. Insulin is the peptide hormone (anabolic] that regulates the metabolism of carbohydrates, fats, and proteins. Upon the breakdown of the natural process of metabolism, the condition leads to hyperglycemia (increased blood glucose levels]. Hyperglycemia demands outsourcing of insulin. The subcutaneous route was found to be the most stable route of insulin administration but faces patient compliance problems. Oral Insulin delivery systems are the patient-centered and innovative novel drug delivery system, eliminating the pain caused by the subcutaneous route of administration. Insulin comes in contact across various barriers in the gastrointestinal tract, which has been discussed in detail in this review. The review describes about the different bioengineered formulations, including microcarriers, nanocarriers, Self-Microemulsifying drug delivery systems (SMEDDs), Self-Nanoemulsifying drug delivery systems (SNEDDs), polymeric micelles, cochleates, etc. Surface modification of the carriers is also possible by developing ligand anchored bioconjugates. A study on evaluation has shown that the carrier systems facilitate drug encapsulation without tampering the properties of insulin. Carrier-mediated transport by the use of natural, semi-synthetic, and synthetic polymers have shown efficient results in drug delivery by protecting insulin from harmful environment. This makes the formulation readily acceptable for a variety of populations. The present review focuses on the properties, barriers present in the GI tract, overcome the barriers, strategies to formulate oral insulin formulation by enhancing the stability and bioavailability of insulin.

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Insulin therapy for diabetes mellitus: Treatment regimens and associated costs

Diabetes & Metabolism ◽

10.1016/j.diabet.2011.10.003 ◽

2012 ◽

Vol 38 (2) ◽

pp. 156-163 ◽

Cited By ~ 16

Author(s):

B. Charbonnel ◽

A. Penfornis ◽

M. Varroud-Vial ◽

O. Kusnik-Joinville ◽

B. Detournay

Keyword(s):

Diabetes Mellitus ◽

Insulin Therapy ◽

Treatment Regimens ◽

Diabetes Mellitus Treatment

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Exosome-Mediated Insulin Delivery for the Potential Treatment of Diabetes Mellitus

Pharmaceutics ◽

10.3390/pharmaceutics13111870 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1870

Author(s):

Belén Rodríguez-Morales ◽

Marilena Antunes-Ricardo ◽

José González-Valdez

Keyword(s):

Diabetes Mellitus ◽

Human Insulin ◽

Insulin Delivery ◽

Dermal Fibroblasts ◽

Therapeutic Drug ◽

Extracellular Medium ◽

Glucose Levels ◽

Wide Range ◽

Diabetes Mellitus Treatment

Exosomes are extracellular nanovesicles between 30 and 150 nm that serve as essential messengers for different biological signaling and pathological processes. After their discovery, a wide range of applications have been developed, especially in therapeutic drug delivery. In this context, the aim of this work was to test the efficiency of exosome-mediated human insulin delivery using exosomes extracted from three different cell lines: hepatocellular carcinoma (HepG2); primary dermal fibroblasts (HDFa) and pancreatic β cells (RIN-m); all are related to the production and/or the ability to sense insulin and to consequently regulate glucose levels in the extracellular medium. The obtained results revealed that the optimal insulin loading efficiency was achieved by a 200 V electroporation, in comparison with incubation at room temperature. Moreover, the maximum in vitro exosome uptake was reached after incubation for 6 h, which slightly decreased 24 h after adding the exosomes. Glucose quantification assays revealed that exosome-mediated incorporation of insulin presented significant differences in HDFa and HepG2 cells, enhancing the transport in HDFa, in comparison with free human insulin effects in the regulation of extracellular glucose levels. No significant differences were found between the treatments in RIN-m cells. Hence, the results suggest that exosomes could potentially become a valuable tool for stable and biocompatible insulin delivery in diabetes mellitus treatment alternatives.

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Drug Delivery Systems for Diabetes Treatment

Current Pharmaceutical Design ◽

10.2174/1381612825666190306153838 ◽

2019 ◽

Vol 25 (2) ◽

pp. 166-173 ◽

Cited By ~ 4

Author(s):

Bozidarka L. Zaric ◽

Milan Obradovic ◽

Emina Sudar-Milovanovic ◽

Jovan Nedeljkovic ◽

Vesna Lazic ◽

...

Keyword(s):

Diabetes Mellitus ◽

Drug Delivery ◽

Drug Release ◽

Vascular Complications ◽

Insulin Delivery ◽

Delivery Systems ◽

Diabetes Treatment ◽

Glucose Levels ◽

Normal Glucose ◽

Nanoparticles Stability

Background:Insulin is essential for the treatment of Type 1 diabetes mellitus (T1DM) and is necessary in numerous cases of Type 2 diabetes mellitus (T2DM). Prolonged administration of anti-diabetic therapy is necessary for the maintenance of the normal glucose levels and thereby preventing vascular complications. A better understanding of the disease per se and the technological progress contribute to the development of new approaches with the aim to achieve better glycemic control.Objective:Current therapies for DM are faced with some challenges. The purpose of this review is to analyze in detail the current trends for insulin delivery systems for diabetes treatment.Results:Contemporary ways have been proposed for the management of both types of diabetes by adequate application of drug via subcutaneous, buccal, oral, ocular, nasal, rectal and pulmonary ways. Development of improved oral administration of insulin is beneficial regarding mimicking physiological pathway of insulin and minimizing the discomfort of the patient. Various nanoparticle carriers for oral and other ways of insulin delivery are currently being developed. Engineered specific properties of nanoparticles (NP): controlling toxicity of NP, stability and drug release, can allow delivery of higher concentration of the drug to the desired location.Conclusions:The successful development of any drug delivery system relies on solving three important issues: toxicity of nanoparticles, stability of nanoparticles, and desired drug release rate at targeted sites. The main goals of future investigations are to improve the existing therapies by pharmacokinetic modifications, development of a fully automatized system to mimic insulin delivery by the pancreas and reduce invasiveness during admission.

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MEtabolic and Renal Effects of AutoMAted Insulin Delivery Systems in Youth With Type 1 Diabetes Mellitus

Case Medical Research ◽

10.31525/ct1-nct03945747 ◽

2019 ◽

Author(s):

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Insulin Delivery ◽

Delivery Systems ◽

Renal Effects

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Insulin therapy in patients with type 2 diabetes mellitus: Treatment to target fasting and postprandial blood glucose levels

Insulin ◽

10.1016/s1557-0843(06)80036-9 ◽

2006 ◽

Vol 1 (4) ◽

pp. 158-165 ◽

Cited By ~ 8

Author(s):

Denis Raccah

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Blood Glucose ◽

Insulin Therapy ◽

Postprandial Blood Glucose ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Diabetes Mellitus Treatment

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Insulin Delivery Systems for Type 1 Diabetes Mellitus - A Comparison Using a Decision Analysis Modeling Approach

Value in Health ◽

10.1016/j.jval.2018.04.1132 ◽

2018 ◽

Vol 21 ◽

pp. S168

Author(s):

P Rai ◽

Y Zhang ◽

A Stover ◽

C Iloabuchi ◽

KM Kamal ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Decision Analysis ◽

Type 1 Diabetes Mellitus ◽

Insulin Delivery ◽

Delivery Systems ◽

Modeling Approach

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Review and Update of Insulin Dependent Diabetes Mellitus

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-8.4.252 ◽

2003 ◽

Vol 8 (4) ◽

pp. 252-265 ◽

Cited By ~ 1

Author(s):

Jennifer Justice Gorrell ◽

Jennifer Schoelles Williams ◽

Paula Powell

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Insulin Therapy ◽

Type 1 Diabetes Mellitus ◽

Therapy Monitoring ◽

Clinical Manifestations ◽

Insulin Delivery ◽

Health Care Practitioner ◽

Diabetes Research

The purpose of this article is to provide the health care practitioner with a comprehensive review of the pathophysiology and treatment of Type 1 Diabetes Mellitus. Traditionally, insulin has been administered via an insulin syringe. In the recent past, diabetes research has focused on developing more convenient insulin delivery devices and longer acting insulin's in hopes of increasing compliance with insulin therapy and improving the management of Type 1 diabetes in both children and adults. Rapidly developing approaches to insulin delivery for Type 1 diabetes continue to be developed at a rapid rate, including administration via continuous subcutaneous insulin infusion in addition to other new approaches. With these advances in therapy, pediatric patients with Type 1 diabetes have been able to achieve strict glycemic control, although the treatment of hypoglycemia remains a burden. The objectives of this article are to the following: to review the epidemiology, risk factors, pathophysiology, clinical manifestations, and diagnostic criteria of Type 1 diabetes mellitus in children,; to discuss the management of these patients, including, insulin therapy, monitoring, diet and exercise, carbohydrate counting and treatment of hypoglycemia,; and to review insulin administration devices, including insulin pens, insulin jet injectors, insulin pumps, and novel insulin delivery systems.

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