This document discusses feedback regulated drug delivery systems, which release drugs in response to physiological triggers. It provides 3 examples: 1) Bio-erosion regulated systems where an enzyme triggers polymer degradation and drug release, 2) Bio-responsive systems where a membrane permeability is controlled by biochemical triggers, and 3) Self-regulated systems using reversible binding to competitively release drugs. One approach discussed uses a cationic hydrogel to release an opioid overdose antidote in response to rising carbon dioxide levels from opioid use. Feedback systems aim to better match drug release to physiological needs compared to traditional delivery.

1. FEEDBACK REGULATED DRUG
DELIVERY SYSTEM
Rate Controlled Drug Delivery System
SUBMITTED TO:
Dr. ANUPAMA DIWAN
SUBMITTED BY:
SURBHI MADAN
(M. PHARM 1ST SEM)

2. Introduction
 The release of drug from delivery system is
activated by a triggering agent, such as a
biochemical substance, in the body and also
regulated by its concentration via some
feedback mechanism.
 Rate of drug release is controlled by the
concentration of triggering agent detected by a
sensor in the feedback regulated mechanisms.

3. Feedback regulated Drug delivery system

4.  Feedback regulated drug delivery concept
was applied to:
1. Bio-erosion-regulated DDS
2. Bio-responsive DDS
3. Self-regulated DDS

5. 1. Bio-erosion-regulated DDS
 The system consisted of drug dispersed bio-
erodible matrix fabricated from poly (vinyl
methyl ether ) half ester, which is coated with a
layer of immobilized Urease, in a solution with
neutral pH polymer erodes very slowly.
 In presence of urea, Urease at the surface of drug
delivery system metabolizes urea to ammonia.
 This causes pH to increase and a rapid
degradation of polymer matrix as well as the
release of drug molecules.

6. Bio-erosion-regulated DDS

7. 2 Bio-responsive DDS
 In this system, the drug reservoir is contained
in a device enclosed by a bio-responsive
polymeric membrane whose drug
permeability is controlled by the
concentration of biochemical agent in the
tissue where the system is located.

9. For Instance : Glucose triggered
Insulin delivery system
 The insulin reservoir is encapsulated within a
hydrogel membrane having pendant -NR2 groups.
 In alkaline solution, -NR2 groups are neutral and
membrane is un-swollen and impermeable to
insulin.
 As Glucose, a triggering agent penetrates into the
membrane to form gluconic acid.
 The - NR2 groups are protonated to form NR2 H+ and
the hydrogen membrane then become swollen and
permeable to insulin molecules.The amount of
insulin delivered is thus bio-responsive to the
concentration of glucose penetration the insulin
delivery system.

10. 3. Self-regulated DDS
 This type of FR-DDS depends on a reversible
and competitive binding mechanism to
activate and to regulate the release of drug .
 In this system the drug reservoir is a drug
complex encapsulated in a impermeable
polymeric membrane.
 The release of drug from the delivery system
is activated by the membrane permeation of
a biochemical agent from the tissue in which
the system is located.

12. Example:
 Reversible binding of sugar molecule by lectin in the design of self
regulating DDS.
 It first involved preparation of Biologically Active insulin derivative in
which insulin I coupled with the sugar(maltose) and this into an insulin-
sugar-lectin Complex.
 The complex is then encapsulated within a semi-permeable membrane .
As blood glucose diffuses in the device and competitively binds at the
sugar binding sites in lectin molecules, this activated the release of
bound insulin-sugar derivatives.
 The released insulin-sugar derivatives then diffuses out of the device
and the amount of insulin sugar derivative depend on the glucose
concentration thus a self regulating drug delivery is achieved.
Drawbacks:
 Release of insulin is non linear in response to the changes in glucose
level.
 A glucose level of 500 mg per dl triggers the release of insulin at only
twice the rate of 50 mg per dl

13. Feedback Regulated Drug Delivery Vehicles:
Carbon Dioxide Responsive Cationic Hydrogels for
Antidote Release.
 An area that requires particular attention
from feedback regulated drug delivery
involves release of antidotes in response to
opioid overdose.
 feedback regulated approaches have been
used effectively in insulin release in response
to changing glucose levels for diabetic
treatments.
 However ,relatively limited work has been
done in the area of opioid overdose.

14.  An opioid typically works by binding to µ-receptors found in the
central nervous system and the gastrointestinal tract.
 The receptors in these organ systems mediate both the
benefits and side effects of opioids.
 Specifically, morphine is an extremely potent drug and this
opiate analgesic relieves pain when delivered in appropriate
amounts.
 However, an overdose of morphine causes hypoventilation,
resulting in increased blood CO2 levels, lowered concentration
of O2, and ultimately acidosis induced death.
 This imbalance of CO2 at high morphine concentrations has
been attributed to the suppression of the activity of carbonic
anhydrase (CA), a metalloenzyme that catalyzes the reversible
hydration of CO2 to HCO3 - and H+, thus, balancing the blood
CO2 levels.
 Naloxone is often used as an antidote to mitigate the risk of morphine
overdose.

15.  Besides the regular polyurethane materials,
many environmental sensitive polyurethanes
were also developed as drug controlled release
carriers, such as temperature sensitive
polyurethane , pH sensitive polyurethane and
pressure sensitive polyurethane , and so on.
 Apart from the controlled release of a specific
drug from a polyurethane matrix, simultaneous
drug release at different rates from
biodegradable polyurethane foams were also
reported

16. REFERENCE
 CHIENY.W. ,“NOVEL DRUG DELIVERY
SYSTEM”, PAGE NO. 1-132
 ROBINSON, “FUNDAMENTALS OF
CONTROLLED DRUG DELIVERY
SYSTEM”,PAGE NO. 482-508