Title:Editorial (Thematic Issue: Nanotechnology as a Strategy to Improve Treatment of Diabetes)
Volume: 15
Issue: 7
Author(s): Antonio J. Ribeiro
Affiliation:
Abstract: Diabetes mellitus is a chronic disease that occurs either when the pancreas does not produce enough insulin and /or when
the body became resistant to insulin actions. Type 1 diabetes (T1DM) (previously known as insulin-dependent, juvenile or
childhood-onset) is characterized by an almost complete loss of insulin mainly due to selective autoimmune destruction of the
pancreatic β-cells and requires daily administration of insulin. Type 2 diabetes (T2DM) (formerly called non-insulin-dependent
or adult-onset) results from insulin resistance and deterioration and βcell function. T2DM comprises 90% of people with diabetes
around the world, and is largely related to excess body weight and physical inactivity. Gestational diabetes is hyperglycemia
that starts or is firstly diagnosed during pregnancy. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)
are intermediate conditions in the transition between normality and diabetes. People with IGT or IFG are at high risk of progressing
to T2DM, although this is not inevitable. Other specific are associated with endocrinopathies, exocrine pancreas disease,
genetic defects of the β-cell or in insulin action has been given [1].
The therapy of T2DM is currently based on 6 approved drug classes encompassing both small molecules [metformin, sulfonylureas,
glitazones, dipeptidyl peptidase-4 (DPP-IV) inhibitors] and proteins [insulin and analogues, glucagon-like polypeptide-
I (GLP-1) and analogues]. Insulin and analogues are potentially administrated by parenteral route, which generally requires
multiple daily injections, not contributing to improve the quality of life of diabetics.
To eliminate the pain and fear associated with injections and increase diabetics compliance, intense research has been done
towards alternative routes that are painless and non-invasive. Generally, drugs delivered by oral route improves disease management,
increase patient compliance and reduces the risk of most diabetes-related complications.
However, therapeutic drugs such as peptides and proteins need to overcome critical hurdles, namely the passage along the
gastrointestinal tract and the transport across intestinal epithelial cells, prior to their beneficial systemic action.
Nanotechnology has opened the possibility of increasing the stability of peptides and proteins and their bioavailability as
well. The development of nanoparticulate delivery systems for insulin has evolved through remarkable advances hardly seen in
the field of drug delivery.
Thus, the present thematic is divided into three main sections addressing the treatment of Diabetes. T1DM, has been treated
by successful transplantation of insulin secreting pancreatic islets. However, serious limitations remain such as the requirement
of immunosuppressive drugs for recipient patients, serious side effects as a result of long term use of drugs, and reduced
functionality of islets at the transplantation site. The use of bioartificial pancreas may be a potentially valid alternative.
The Kizikel’s group addressed current progress and obstacles for the development of a bioartificial pancreas using micro- and
nano based systems for encapsulation of islets.
T2DM is one of the most prevalent and rapidly spreading diseases worldwide. The incretin based therapies for T2DM are
now widely investigated and used, and mainly include incretin hormones which are glucose-dependent insulinotropic peptide
(GIP) and GLP-1 released from the endocrinal cells in small intestine in response to food intake. Araujo et al. highlighted the
use of micro and nanosystems to efficiently deliver the incretins orally. T2DM is a progressive disease, and most patients, as it
happens in T1DM, will eventually need treatment with exogenous insulin. The therapeutic goal of the treatment with insulin is
to reproduce, as accurately as possible, the physiological pattern of insulin secretion, in order to control glycemia. In former
times, the emphasis of oral delivery of insulin was more on convenience and avoidance of needles. Taking into account the current
understanding of the pathogenesis of diabetes, additional emphasis has been given to the oral delivery of insulin as the
most physiological mimicking way to deliver exogenous insulin to its site(s) of action in the target tissues and cells.
The third section includes two articles that discuss different barriers encountered by insulin nanoparticles in the gastrointestinal
tract and nanosystems being used for oral delivery for insulin toward clinical trials and industrial development, respectively.
Lopes at al. speculated about the role of nanoparticles in the insulin transport across intestinal epithelium, besides explore
their likely pathways and analyze published experimental results on the bioavailability (BA) and pharmacological activity
(PA) of oral insulin. Cabral’s group described nanosystems that provide oral insulin release, and mitigated advantages ascribed
to those nanosystems with evident economic and industrial feasibility.