Resealed Erythrocytes : A Novel Drug Delivery System

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Erythrocytes, also known as red blood cells, have been extensively studied for their potential carrier capabilities for the delivery of drugs and drug-loaded microspheres. Such drug-loaded carrier erythrocytes are prepared simply by collecting blood samples from the organism of interest, separating erythrocytes from plasma, entrapping drug in the erythrocytes, and resealing the resultant cellular carriers. Hence, these carriers are called resealed erythrocytes. The overall process is based on the response of these cells under osmotic conditions. Upon reinjection, the drug-loaded erythrocytes serve as slow circulating depots and target the drugs to a reticuloendothelial system. These resealed erythrocytes are used for slow drug release, drug targeting actions like targeting the liver, reticuloendothelial system, etc., treatment of hepatic tumors, removal of toxic agents, delivery of antiviral agents, etc. The use of resealed erythrocytes looks promising for a safe and sure delivery of various drugs for passive and active targeting. I had discussed about source and isolation of erythrocytes, methods of drug loading, advantages of erythrocytes as drug carriers, in vitro and in vivo characterization, applications and novel approaches.

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Comments

Shreesha Bhat's picture

a nice presentation ma'am. i had some questions:
1) as per your presentation,the shelf life, (i.e in vitro storage) is two weeks, then wont there be a problem in making this product available all over the world? are there any means for its extended storage?
2) are there any products of resealed erythrocytes in the market?

Shreesha V Bhat Ramanbhai Patel College of Pharmacy, Education campus Changa, Gujarat, India. http://www.pharmainfo.net/shreeshabhat

prathyusha's picture

1) Membrane stabilizing agents are used to improve the storage of resealed erythrocytes. eg of stabilizing agents are dimethyl sulfoxide, dimethyl-3,3-dithio-bis-propionamide, toluene-2,4-diisocyanate,etc. After exposing the resealed erythrocytes to any of these stabilizing agents,they are lyophylized. This will increase the stability upto atleast 1month. But the main disadvantage of using membrane stabilizers is that they will reduce the circulation time. Other methods to improve the stability include encapsulation of prodrug that undergoes conversin into parent drug only at body temperature, high glycerol freezing technique and reversible immobilization in alginate or gelatin gels.

prathyusha's picture

yes i have quoted the examples of the drugs most of them are marketed itself.

Komal Nikam's picture

daer MAM,
NICE PPT,
CAN U EXPLAIN STABILITY ASPECTS OF RESELEAED ERYTHROCYTES?

prathyusha's picture

1.The morphology of erythrocytes decides their life span after administration.
2. Shape changes(deformities) also affects the life span.This parameter evaluates the ease of passage of erythrocytes through narrow capillaries.
3. Osmotic fragility and turbulance fragility will influence integrity of cell membrane.
4.Drug content and drug release pattern are also need to be considered.

Bhasker's picture

Hi Pratyusha,
I have the following queries:
1.What are the standard limits for Biological characterization of resealed erythrocytes?
2.You have mentioned there is no toxicity for resealed erythrocytes in 1 of your slides.Are the cells used from monkeys,rabbit etc are relatively non antigenic?
3.How can we enhance the circulation t1/2 of these erythrocytes as membrane stabilizers in bound form remarkably reduces circulation survival time?

Varsha Bansode's picture

Dear Prathyusha,
I have some questions as following,
1.what are the disadvantages of this method
2.Is there any marketed preparation of resealed erythrocytes?(mention brand name)
3.what criterias or characteristics of drugs will you take into consideration while going for this method?

Sanykale's picture

For this kind of application, what should be purity or fold purity of erythrocytes over other blood cells required?

Can we use RBC from one individual to another? will there be immunogenic response and if yes what is feasibility of such technology for treatment?

Dr.Sandeep Bhaskar Kale
http://www.pharmainfo.net/sanykale123

Jithan Aukunuru's picture

can you cite any clinical trials conducted with resealed erythrocytes?

Sirisha Pingali's picture

dear pratyusha,,
Good presentation..
Coming to the queries..
What is the life span of these erythrocytes in the body? are they degraded naturally??
What are the advantages of using Resealed erythrocytes over other NDDS like liposomes??

Sirisha Pingali

http://www.pharmainfo.net/sirisha

Viswanadha Institute of Pharmaceutical Sciences.

www.vnips.edu.in

Dixon Thomas's picture

Dear Prathyusha, it's very nice concept.
But I don't understand how RBCs become the most abundant cells in the body, please give the statistics?

Mr. Dixon Thomas, M. Pharm, M. S., RPh Assoc. Prof., RIPER 

 

Dr. T.E.G.K. Murthy's picture

what about its storage?
after the particular life span they are use less?
what abt its availability?

Dr.T.E.G.K.Murthy
http://www.pharmainfo.net/tegkmurthy/biography
Principal
Bapatla College of Pharmacy, Bapatla

Khushbu Hasmukh Patel's picture

how this drug delivery system is better than other?
Futute of it & stability aspects of resealed erythrocytes?

K.H.Patel.
My profile link is
http://www.pharmainfo.net/khushbu-hasmukh-patel

R.S.Prakasham's picture

Any study on cross-reactivity of erythrocytes? What is its life span and drug releasing capacity?

Komal Nikam's picture

Hy
which drugs r not resealed in erythocytes? What r the size specification & diff factors affect on it?

Komal Nikam's picture

HY,

please give some examples of marketed formulation of this system?

G.Sailesh's picture

what are the factors to be considered while formulating a drug into a resealed erythrocyte? Any disadvantages of resealed erythrocytes?

abherids86's picture

How does osmolality of resealing buffer and temperature influence the performance of carrier erythrocytes?

Hemangi Purarkar's picture

1.How these erythrocytes prepared and what are the parameters considered while preparation?
2. Is there any drug interaction ?
3. How the safety of this released erythrocytes proved and what are the safety parameters measures when it says to be absolutely safe or having no side effects?

Ayush Singhal's picture

1)When they are introduced again after resealing and it will follow the same cycle of RBC metabolism??
2)As erythrocytes are taken from a donar, is there any factor like compatability between a donar & acceptor?
3) a) Can resealed erythrocytes be used for a target specific drug delivery purpose??

b) If yes please mention how you will perform this???

Ayush A. Singhal RPCP, CHANGA GUJARAT http://www.pharmainfo.net/ayushsinghal/biography

Pavan Kumar Alapati's picture

can u list out some Physical and Chemical methods used to break the erythrocytes for drug loading.

vishal.bairwa's picture

Dear Pratyusha,

Nice presentation. I wanna knw that can we administer the radioactive compounds in the resealed erythrocytes and if yes then whether such preparations are tried ever for treating the targetted cancer treatment?
What will be the time bound expiry period we need to follow for the drugs which are to be sealed into the erythrocytes ?

Thankyou....

pragathi's picture

can you explain about its storage, and availability rate ?

Komal Nikam's picture

Hello,

-Can u please tell me the composition of Hank's balance salt solution ?
-Also Give me some eg of ACE inhibitor which r loaded in erythrocytes?

Regards,
Komal

Komal Nikam's picture

Hello,

-generaly after loading erythrocytes converted into stamatocytes,spherocyte or echinocytes so which r the drugs produce this kind of RBC?

-Also imp.s of buffer in its preparation?

Komal Nikam's picture

Mam,

how invitro characterization help in resealed erythrocyte?

Suhaas's picture

1. Out of different methods, which method is more suitable for high entrapment efficiency?
2. What is the role of haemoglobin in the fate of resealed erythrocytes?
3. What are the advantages of magnet incorporating resealed erythrocytes over normal resealed erythrocytes?
4. What are the recent innovations in resealed erythrocytes?

Suhaas

RAVI TEJA's picture

As the drug is sealed in the Erythrocyte and released into the body, if they rupture with another cell and release the drug at that site which is not the actual place to deliver the drug, then what are the chances to overcome this problem???????

Thank you,

roshanpharma's picture

give me some disadvantages of this NDDS

Pavan Kumar Alapati's picture

can u list out major disadvantages?

Vamsikrishna Reddy's picture

how much drug can be loaded in resealed erythrocytes and which drugs can be suitable for it.

B.Vamsikrishna Reddy

VOLETI VIJAYA KUMAR's picture

what are all main uses

VIJAYA KUMAR.VOLETI M.Pharmacy

Asst Professor

Raos college of Pharamcy

Nellore