A Drug carrier for constant rate Insulin release for basal insulin therapy was designed such that it
mimics the physiological insulin secretion. The initial burst release, which causes a significant issue
with other release techniques, was effectively avoided. Additionally, the plasma drug level can be
sustained for an extended period of time.
A better glycemic control…?
Diabetes cannot be cured, at least till now, the only way to deal with it is through tight glycemic
control. To achieve this goal, an ideal insulin therapy should mimic the normal physiologic secretion
of insulin, which consists of a sustained low level throughout the day (basal insulin) and relatively large
bursts after meals (bolus insulin).
To attain this goal, various technologies have been proposed, such as self-regulated insulin
release, insulin pumps, and so on. Among these methods, basal-bolus insulin therapy, in which rapidacting insulin is given before each meal to mimic bolus insulin for postprandial glucose control and
long-acting insulin is given at bedtime to mimic basal insulin for fasting plasma glucose control, is the
most practical and has become the gold standard in the treatment of diabetes.
Zero order Insulin release
First PEG-insulin conjugates were created. The
LBL films (layer by layer) were then made from
the conjugate and TA, with hydrogen bonding
between the PEG chain and the TA(Tannic acid)
acting as a driving force. When immersed in
aqueous solutions, the films progressively
breakdown and release PEG-insulin.
Conjugation of PEG chains onto insulin improves
the drug's physical and pharmacological
properties but has no significant effect on the
drug's in vivo potency. The kinetics of PEGinsulin release are zero-order.
What’s new?
As can be seen, the release behaviour of the PEGinsulin/TA films differs significantly from that of typical
drug carriers. Until now, most drug carriers have
reported drug release in a fast-then-slow pattern. Some carriers were reported to follow a zero-order release kinetics, but the release rate can be regarded constant only at a certain part of the release process.
The PEG-insulin/TA films' distinct release
behaviour can be explained by their distinct drug release mechanism. Ordinary drug carriers release the drug
through diffusion or breakdown of the carrier matrix. In contrast, the PEGinsulin/TA films in this study release PEG-insulin through the film's progressive disintegration.
Complications free…?
After the evaluation of biocompatibility studies, it didn’t show any wound infections. Histological
studies also indicate compared to untreated control, only a slightly increased number of inflammatory
cells were observed in the sample, suggesting it causes only a minor inflammatory response.
Final Thoughts…
By first PEGylating insulin and then integrating the conjugate into layer-by-layer constructed films
using tannic acid, a novel drug carrier was created (TA). Because the PEG-insulin and TA in the films
were coupled with reversible, dynamic hydrogen bonds, when soaked in aqueous solutions, the films
gradually dissolve, releasing PEG-insulin into the medium. In vitro release assays demonstrated that
PEG-insulin release followed a zero-order kinetics. A zero-order kinetics is further supported by
theoretical study based on the unique release mechanism. In vivo experiments utilising a
streptozotocin-induced diabetic rat model revealed that subcutaneous implantation of the film could
maintain a consistent plasma drug level and thereby keep fasting blood glucose levels (BGL) close to
normal.
Fasting BGL (Blood Glucose Level) can be reduced to near normal levels for an extended period
of time using this therapy. The length of action is determined by the thickness of the film. Fasting BGL
was controlled within the normoglycemic range for 16 days using a 50-bilayer film.
The next step…
Further research into the creation of an injectable drug carrier using microspheres rather than
macroscopic substrates for LBL assembly is underway.
Reference:
Blog by Nirbhay Mourya
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