Sensitiveness to internal or external signals of the body can be achieved by means of materials (mostly

polymers, but also lipids and metals) that modify their properties as a function of the intensity of the
signal and that enable the transduction into changes in the delivery system that affect its ability to
host/release a therapeutic substance.

Polymers widely used because they can be prepared with an unequalled richness of structures and
functional groups i.e. highly customizable. Works by making polymers that have functional groups that
modify properties as function of intensity. This Is all thermodynamics.

Possible changes i) modifications of solubility, shape etc ii) reversible change in conformation of cross-
linkings changes affinity toward other chemicals iii) reversible stretching/shrinking of surface
immobilized chains. smart when these are reversible & proportional to stimulus.

Pharmacological treatments require active substance in high and constant enough concentration for
therapeutic effect. Existing sustained-release medicines release at pre-established rate.
Generation 1 rate programed, generation 2 activation modulated, generation 3 feedback released

Drugs can be materialized at macro,micro,nano scales. Macro: placed in organ using invasive approach
(think the brain thing). Nanoparticles open possibility of systemic administration but releast @ specific
cells.

More of a drug delivery system rather than a dosage form. Runs parallel to development of excipients.

One can point out several reasons for such slow incorporation of nanocarriers, in particular, stimuli-
responsive DDSs, to the therapeutics. A relevant one is the difficulty to follow one key principle of the
pharmaceutical industry: quality control. Most materials are synthesized under poorly reproducible
conditions and the methods to prepare the smart DDSs are not standardized. In this sense, regulatory
agencies are still working on guidances for preparation and evaluation of nanosized materials.

Also because combination fo polymers lipids and silica are considered new excipients because of their
reactions in the body, there are more paper work and stuff regarding cytotoxicity genotoxicity etc.
analytics hard because bioavailability must be measured in target tissue or cesll, not systemically.
Transplantation:

Pancreas transplantation is a proven therapeutic treatment option for adults with insulin dependent
diabtes. Superior to intensive insulin therapy with regard to achieving normal glucose level control.
Despite improving outcomes for patient and graft survival, rate of pancreas transplants steadily
decreased since 2000s.

Simulataneous because patients often have kidney disease that is owing to diabetes. As long as patient
is healthy enough, benefits of adding pancreas to help diabetes can also proong survival of transplanted
kidney, because it is protected yb pancreas from development of recurrent diabetic damage to kidney.
Also risk of immunosuppression out of picture b/c same as for kidney transplant.

PAK to patients who had kidney surgery already, or had SPK and lost pancreas.

PTA, have normal kidney. Are risk of immunosuppression outweigh risk of diabetes treated with
intensive insulin therapy?
Potential early complications: many, namely thrombosis, hemorrhage of pancreatic graft. Infection,
metabolic (hypocalcemia), etc, Typically present in first month.

Half life increasing constantly now 14 years, things like improved surgical procedure,
immunosuppression, donor selection, etc.

Endocrinology community emphasize consideration for patients byond those with advanced kidney
disease.