This document discusses feedback-regulated drug delivery systems (FRDDS), which release drugs in response to triggers in the body. It describes three types of FRDDS: 1) bioerosion-regulated systems that degrade in response to pH changes from enzymes, 2) bioresponsive systems using membranes that become permeable to drugs in response to biochemicals, and 3) self-regulating systems using reversible binding of drugs to biochemical triggers to control release. Examples are given for each type including insulin delivery systems responsive to glucose. Diagrams illustrate components and mechanisms of the different FRDDS types.

1. SRI ADICHUNCHANAGIRI COLLEGE OF PHARMACY B G NAGAR
SEMINAR 0N:
FEEDBACK REGULATED DRUG
DELIVERY SYSTEM
PRASHANTA TAVARI
M.PHARM 1ST YEAR
DEPT OF PHARMACEUTICS
SACP

2. FEEDBACK-REGULATED DRUG DELIVERY
SYSTEM
 In this group of CrDDSs, the release of drug molecules
is activated by a triggering agent, such as a biochemical
substance, in the body via some feedback mechanisms.
 The rate of drug release is regulated by the concentration
of a triggering agent detected by a sensor
built into the CrDDS.

3. CLASSIFICATION
1. Bioerosion–regulated drug delivery system
2. Bioresponsive drug delivery system
3. Self–regulating drug delivery system

4. 1.Bioerosion–regulated drug delivery system
.Heller and Trescony developed bioerosion-regulated drug
delivery system.
.This CrDDS consists of a drug-dispersed bioerodible matrix
fabricated from poly(vinyl methyl ether) half-ester, which
was coated with a layer of immobilized urease.
.In a solution with near neutral pH, the polymer erodes
very slowly.
. In the presence of urea, urease at the surface of the drug
delivery system metabolizes urea to form ammonia.

5.  This causes the pH to increase and activates a rapid degradation
of polymer matrix as well as the release of drug molecules.
Fig:- Cross-sectional view of a bioerosion-regulated
hydrocortisone delivery system, a feedback-regulated drug
delivery system, showing the drug-dispersed monolithic
bioerodible polymer matrix with surface-immobilized
ureases

6. 2.Bioresponsive drug delivery system
 The feedback-regulated drug delivery concept has also been
applied to the development of a bioresponsive CrDDS by
Horbett.
 In this CrDDS, the drug reservoir is contained in a device
enclosed by a bioresponsive polymeric membrane whose
permeability to drug molecules is controlled by the
concentration of a biochemical agent in the tissue where the
CrDDS is located.

7.  A typical example of this bioresponsive CrDDS is the
development of a glucose-triggered insulin delivery system, in
which the insulin reservoir is encapsulated within a hydrogel
membrane containing pendant NR2 groups.
 In an alkaline solution, the NR2 groups exist at neutral state
and the membrane is unswollen and thus impermeable to
insulin.
 As glucose penetrates into the membrane, it is oxidized
enzymatically by the glucose oxidase entrapped in the
membrane to form gluconic acid.

8.  This process triggers the protonation of NR2 groups to form
NR2H+, and the hydrogel membrane becomes swollen and is
thus permeable to insulin molecules.
 The amount of insulin delivered is bioresponsive to the
concentration of glucose penetrating into the CrDDS.

9. Fig:- Cross-sectional view of a bioresponsive insulin
delivery system, a feedback-regulated drug delivery system,
showing the glucose oxidase-entrapped hydrogel membrane
constructed from amine-containing hydrophilic polymer.
The mechanism of insulin release, in response to the influx
of glucose, is also illustrated.

10. 3.Self–regulating drug delivery system
 This type of feedback-regulated CrDDS depends on a reversible
and competitive binding mechanism to activate and to regulate
the release of drug.
 A drug complex is encapsulated within a semipermeable
polymeric membrane.
 The release of drug from the CrDDS is activated by the
membrane permeation of a biochemical agent from the tissue
where the CrDDS is located.
 Kim et al, first applied the mechanism of reversible binding of
sugar molecules with lectin.

11.  For this CrDDS,
 a biologically-active insulin derivative, in which insulin is
coupled with a sugar (e.g., maltose), was first prepared and then
conjugated with lectin to form an insulin–sugar–lectin
complex.
 This complex is then encapsulated within a semipermeable
membrane.
 As blood glucose diffuses into the CrDDS, it binds,
competitively, with the binding sites in the lectin molecules and
activates the release of the insulin–sugar derivatives from the
binding sites.
 The amount of insulin-sugar derivatives released depends on
the concentration of glucose. Thus, a self-regulating drug
delivery is achieved.

12.  Further development of the self-regulating insulin delivery
system has utilized the complex of glycosylated insulin–
concanavalin A, which is encapsulated inside a polymer
membrane.
 As glucose penetrates into the system, it activates the release of
glycosylated insulin from the complex for a controlled release
from the system.
 The amount of insulin released is thus self-regulated by the
concentration of glucose that has penetrated into the insulin
delivery system.

13. Fig:- Various components of a self-regulating
insulin delivery system, a feedback-regulated
drug delivery system.

14. REFERENCE
1. Novel Drug Delivery System By Yie W. Chien
second edition
2. Controlled and Novel Drug Delivery By
N.K.Jain

15. Thank you