Barriers encountered in drug delivery

its about the barriers for drug delivery and how to overcome them.

1. BARRIERS ENCOUNTERED IN DRUG DELIVERY NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH 1 PRACHI JOSHI M.S.PHARM PHARMACEUTICS I ST SEM I.D. NO. 310/14

2. CONTENTS INTRODUCTION BARRIERS PHYSIOLOGICAL BARRIERS BIOCHEMICAL BARRIERS CHEMICAL AND PHYSICOCHEMICAL BARRIERS METHODS OF OVERCOMING BARRIERS CONCLUSION REFERENCES 2

3. INTRODUCTION From many years researchers and scientists are working a lot on the drug discovery. Many of the potent drugs have been yet discovered but still the given drug dosen’t reach the site of action especially the drugs given orally because of barriers present in body and due to drug properties. And this problem also persist with biotechnological products like peptides, proteins etc. 3

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5. PHYSIOLOGICAL BARRIER Blood brain barrier : The blood-brain barrier (BBB) is a membrane that controls the passage of substances from the blood into the central nervous system. Intestinal epithelium : The intestinal epithelium is a single-cell layer, largest and most important barrier against the external environment. Blood ocular barrier: The blood-ocular barrier is a barrier created by endothelium of capillaries of the retina and iris, cilliary epithelium. Skin : The physical barrier is mainly located in the stratum corneum and consists of protein-enriched cells and lipid-enriched intercellular domains. 5

6. BIOCHEMICAL BARRIERS Metabolizing enzymes : In the lumen of stomach, a mixture of hydrochloric acid and proteolytic pepsins is the first metabolic barrier and the enzymes of the upper small intestine act as second barrier. Transporter and efflux pump : Substrate can be transported through the brush border membrane in a carrier-mediated and pH-dependent manner. P-glycoprotein (P- gp ) is a known MRP(multi resistance protein) that serves as an efflux pump. 6

7. CHEMICAL BARRIERS Hydrogen bonding potential : A hydrogen bond is the attractive force between the hydrogen attached to an electronegative atom of one molecule and an electronegative atom of a different molecule. Hydrogen bonding is a key contributor to the specificity of intramolecular and intermolecular interactions in biological systems. PHYSICOCHEMICAL PROPERTIES OF DRUG Physicochemical properties of drug are also important determinants in the passage of drugs via the paracellular path. The physicochemical properties such as solubility, ionization lipophilicity , permeability, etc. are important for determination of drug action. 7

8. METHODS TO OVERCOME BARRIERS 1.PHYSICAL METHODS In physical method some external stimuli are applied to open the barrier it includes ultrasound, iontophoresis , stripping etc. Ultrasound, microwave or electromagnetic fields that can be used to open the blood brain barrier. M icrowave irradiation facilitated central effects of domperidone by altering the permeability of blood brain barrier and enhancing the entry of drug into the CNS. Stripping is a technique used to remove stratum corneum by application of adhesive tape or cyanoacrylate Glue. Iontophoresis and electroporation require electrical forces for drug delivery across stratum corneum . 8

9. 2. CHEMICAL METHOD Chemical method involves the use of chemicals to increase the permeability of the barrier. A large number of absorption enhancers have been studied, such as fatty acids, bile salts, enamine derivatives of phenylglycine , esters, ethers, salicylates . Mostly used blood brain barrier opening practice is via arterial injection of hyperosmolar solution (e.g. mannitol , arabinose ). Chemical enhancers for skin include the compounds that interact with the lipid matrix of the stratum corneum to alter its nanostructure and thereby increase permeability. The most common chemical enhancer is water, which leads to hydration of the stratum corneum . Solvents, such as ethanol, methanol, chloroform and acetone, as well as detergents increases the permeability of stratum corneum . 9

10. 3 . BIOCHEMICAL METHOD Biochemical method involves the biological molecule as permeability enhancer. A 45kDa biological molecule zonula occludens toxin ( Zot ), an active tight junction modulator at the blood brain barrier. It also permits an enhanced transport of the therapeutic agents doxorubicin and paclitaxel . Magainin , a naturally occurring pore-forming peptide increase skin permeability by direct interaction with and disruption of stratum corneum lipids. 10

11. DRUG DELIVERY BY FORMULATIONS COLLODIAL DRUG CARRIERS : Colloidal drug carriers include micelles, emulsions, liposomes and nanoparticles . BIODEGREDABLE NANOPARTICLES : Biodegradable nanoparticles formulated from poly (D,L- lactide -co- glycolide ) (PLGA) are used for sustained and targeted delivery of different agents including plasmid DNA, proteins and peptides and low weight molecules. LIPOSOMES: Liposomes are small vesicles that are composed of unilamellar or multilamellar phospholipids bilayers surrounded by aqueous compartments. PRODRUG : The prodrug are used to overcome various barriers which can hinder drug delivery, including solubility. 11

12. CONCLUSION The absorption of an orally administered drug depends on its passage through several barriers to deliver drug. The drug can pass either between or through the cells, depending on its physicochemical properties. Overcoming these barriers help in the development of improved drug delivery systems to treat different diseases conditions. Although many challenges exist in transporting the drug from different barriers, that’s why pharmaceutical scientists and medicinal chemists are overcoming them with new drug delivery system that enhance drug delivery. 12

13. REFERENCE Calcagno AM and Siahaan TJ. Physiological, Biochemical, and Chemical Barriers to Oral Drug Delivery. Wang B, Siahaan TJ, Soltero R. Drug Delivery Principles and Application. John Wiley and Sons, Inc. Publications.16-24 Valentino SJ , Nti-Addae KW. Prodrug strategies to overcome poor water solubility. Advanced drug delivery reviews.2007;59(7):677,679,687 Chen Y, Liu L. Modern methods for delivery of drugs across the blood–brain barrier. Advanced Drug Delivery Reviews.2012;64:647-650 Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Advanced Drug Delivery Reviews.2006;58(11):1133 13

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