Insulin Delivery

Objectives:To systematically review whether the mode of intensive insulin therapy (continuous subcutaneous insulin infusion [CSII] vs. multiple daily injections [MDI]) and/or the mode of blood glucose monitoring (real time-continuous glucose monitoring [rt-CGM] vs. self-monitoring of blood glucose [SMBG]) results in better glycemic control, less hypoglycemia, improved quality of life, and improved clinical outcomes in individuals with type 1 diabetes, type 2 diabetes, and pre-existing diabetes in pregnancy.

Objectives: To systematically review whether the mode of intensive insulin therapy (continuous subcutaneous insulin infusion [CSII] vs. multiple daily injections [MDI]) and/or the mode of blood glucose monitoring (real time-continuous glucose monitoring [rt-CGM] vs. self-monitoring of blood glucose [SMBG]) results in better glycemic control, less hypoglycemia, improved quality of life, and improved clinical outcomes in individuals with type 1 diabetes, type 2 diabetes, and pre-existing diabetes in pregnancy.

Diabetes is generally divided into the categories ‘type 1 diabetes’ and ‘type 2 diabetes’. They have much in common with each other, but differ in the cause and urgency of treatment necessary (see Table 1.1). As a broad generalization, type 1 diabetes occurs in those who are generally younger, so children and teenagers are more likely to have type 1 diabetes, and those in middle age type 2. It is also true that those with type 1 diabetes are generally of normal weight, while overweight is common in those with type 2. It is certain that overweight is a risk for type 2 diabetes, and not for type 1.

Diabetes is one of the leading lethal diseases, which is often treated by hypodermic injection of insulin or by oral delivery. Oral drug delivery systems show limitations due to poor absorption and degradation that occurs in the GI tract and in the liver. Due to the patient discomfort that leads to poor patient compliance , alternative methods to administer insulin are of great interest. In recent years, much attention has been paid to transdermal delivery devices because of drug delivery reliability to a target site with patient-friendly technologies. The major part of integumentary systems is skin, but skin drug delivery is challenging due to barrier properties exhibited by the outermost layer of skin stratum corneum. Transdermal drug delivery systems (TDDS) control the rate of release of the drug into the patient so that blood concentration maintains a steady state, and gastrointestinal absorption is avoidable. Controlled drug release causes minimum side effects and improves bioavailability of drugs, which showed poorly bioavailable drugs over other routes of delivery. The limiting factor in TDDS is stratum corneum, which is the outer layer of the skin and which acts as an effective barrier to the transport of biomolecules into the skin. For this reason, an effective method for drug delivery is hypodermic injection, which is a painful delivery. Besides, it needs a high level of expertise to administer the injection and the occasional risk of infections acquired through needle sticks. In recent year ' s microneedle (MN)-mediated drug delivery systems have been developed which can meet all the above goals. Microneedles are microscopic needles, which can deliver the drug to the target site by the degradation or dissolution of the polymer in the skin after insertion. This results in delivery of the encapsulated molecules, and no needles are left afterward. Microneedles are large and strong enough to insert into the skin and to deliver drugs into the skin, but they are short enough so that they do not reach the deeper layers of the skin to cause nerves stimulation. Microneedles offer an efficient and attractive method for delivering several classes of biomolecules and drugs to the skin in a self-administered manner. The overall goal of this research is TDDS and polymer micromodels system for insulin drug delivery, which can deliver an active biopharmaceutical in vivo for producing the desired physiological response. GRAPHIC ABSTRACT ARTICLE HISTORY

The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a nanocomplex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer. The selected CPP was octaarginine (r8), chemically conjugated with cholesterol (Chol) or lauric acid (C12), whereas the protecting polymer was poly (glutamic acid)-poly (ethylene glycol) (PGA-PEG). This enveloping material was intended to preserve the stability of the nanocomplex in the intestinal medium and facilitate its diffusion across the intestinal mucus. The enveloped nanocomplexes (ENCPs) exhibited a number of key features, namely (i) a unimodal size distribution with a mean size of 200 nm and a neutral zeta potential, (ii) the capacity to associate insulin (~100% association efficiency) and protect it from degradation in simulated intestinal fluids, (iii) the ability to diffuse through intestinal mucus and, most importantly, (iv) the capacity to interact with the Caco-2 model epithelium, resulting in a massive insulin cell uptake (47.59 ± 5.79%). This enhanced accumulation of insulin at the epithelial level was not translated into an enhanced insulin transport. In fact, only 2% of insulin was transported across the monolayer, and this was correlated with a moderate response of insulin following oral administration to healthy rats. Despite of this, the accumulation of the insulin-loaded nanocarriers in the intestinal mucosa could be verified in vivo upon their labeling with 99mTc. Overall, these data underline the capacity of the nanocarriers to overcome substantial barriers associated to the oral modality of administration and to facilitate the accumulation of the associated peptide at the intestinal level.

Objectives To compare the health-related quality of life (HRQOL) of youths on injection regimens to those prescribed insulin pump therapy and examine factors related to HRQOL in youths with type 1 diabetes. Methods An ethnically diverse group of youths (n = 160, ages 5–17 years) with type 1 diabetes and their caretakers completed family, parent, and child adjustment measures, as well as measures of generic- and disease-specific HRQOL. Metabolic control and regimen information were assessed through medical records. Results HRQOL was unrelated to regimen prescription. Child, family, and parent adjustment variables were significantly related to HRQOL, whereas other demographic and clinical variables were relatively less important. Conclusions Present findings indicate that insulin pump therapy does not have negative implications for HRQOL. They also suggest that interventions aiming to improve HRQOL in this population should target child, parent, and family adjustment and not focus solely on disease-related outcomes.

The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a nanocomplex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer. The selected CPP was octaarginine (r8), chemically conjugated with cholesterol (Chol) or lauric acid (C12), whereas the protecting polymer was poly (glutamic acid)-poly (ethylene glycol) (PGA-PEG). This enveloping material was intended to preserve the stability of the nanocomplex in the intestinal medium and facilitate its diffusion across the intestinal mucus. The enveloped nanocomplexes (ENCPs) exhibited a number of key features, namely (i...

The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a nanocomplex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer. The selected CPP was octaarginine (r8), chemically conjugated with cholesterol (Chol) or lauric acid (C12), whereas the protecting polymer was poly (glutamic acid)-poly (ethylene glycol) (PGA-PEG). This enveloping material was intended to preserve the stability of the nanocomplex in the intestinal medium and facilitate its diffusion across the intestinal mucus. The enveloped nanocomplexes (ENCPs) exhibited a number of key features, namely (i...

The Artificial Pancreas is a medical device, currently in development, that aims to provide automatic regulation of blood glucose (BG) levels in ambulatory type 1 diabetes mellitus sufferers. The most popular approach utilises subcutaneous (SC) continuous glucose monitoring (CGM) combined with SC insulin injection controlled by a Model Predictive Control (MPC) algorithm. From a safety risk perspective problematic elements include the performance robustness of the CGM and the need for a pre-meal insulin bolus to provide satisfactory post prandial BG regulation. This contribution presents preliminary in silico studies which indicate that the use of an alternative approach to insulin delivery - intra-peritoneal (IP) infusion - could provide a similar level of BG regulation (as obtained with SC delivery), without the need for the pre-meal bolus. This simplified control architecture would remove the patient safety risk related to the administration (or not) of pre-meal bolus.