PROTEIN & PEPTIDE DELIVERY SYSTEM FORMULATION

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1. PROTEIN & PEPTIDE DELIVERY PREPARED BY : TEJAL ASHOK SHINDE FIRST YEAR M PHARM DEPT. OF PHARMACEUTICS VIPER, ALE .

2. CONTENTS INTRODUCTION OF PROTEIN & PEPTIDE BARRIERS OF PROTEIN DELIVERY FORMULATION OF DRUG DELIVERY EVALUATION OF DRUG DELIVERY OTHER MACROMOLECULES

3. PROTEIN & PEPTIDE PROTEINS – proteins are the large organic compound made up of amino acid linear chain & joined together by peptide bonds. Protein > 50 amino acids PEPTIDES- These are short polymer formed from the linking , in a defined order of amino acids. peptides < 50 amino acids

4. FUNCTION OF PROTEINS Transport & storage of small molecules. Mechanical support form fibrous protein. Generation & transmission nerve impulses. Immune protection through antibodies. Control of growth & differentiation via hormones.

5. BARRIERS OF PROTEIN DELIVERY Enzymatic barrier Intestinal epithelial barrier Capillary endothelial barrier Blood brain barrier Biological barrier

6. Enzymatic barrier – Hydrolytic cleavage : Chemical modification : Hydrolytic cleavage : peptides bonds by process such as insulin degrading enzyme converting enzyme & renin. There should be irreversible reaction. potentially causes of damage protein & peptide drug. Chemical modification : protein such as phosphoxylation by oxidation by oxidase. Its limits absorption of protein drugs from GI tracts.

7. Intestinal epithelial barrier – barrier for transport of protein drug across the intestinal epithelial. Several mechanisms: Passive & Carrier medicated Endocytosis & transcytosis Paracellular

8. Capillary endothelial barrier – To cross capillary endothelial the peptides / proteins must pass between the cells. Transfer across endothelial cells themselves. Membranes may get modified cytoplasmic enzymes. Blood brain barrier – Monolayer cells together tight junctions. Allow passage small, hypophilic & gases. Large molecules do not pass BBB easily.

9. FORMULATION OF DRUG DELIVERY The oral delivery of therapeutic proteins & peptides can be successfully achieved by using various carrier system like: DRY EMULSIONS –dry emulsion is prepared by drying liquid o/w emulsion containing a solid carrier in the aqueous phase. CELLULAR CARRIER ( eg. Resealed erythrocytes) MICROSPHERE LIPOSOME NANOPARTICES HYDROGELS ( drugs enclosed in gelling polymers)

10. EVALUATION OF DRUG DELIVERY Stability testing. Bioassay. UV spectroscopy. Bradford assay. Differential scanning calorimetry. Chromatography. Electrophoresis.

11. Stability testing: The capability of a particular formulation in a specific container/closure system to remain within its physical , chemical , microbiological toxicological and protective specification. Bioassay: Due to complexity of proteins, bioassay are required to assess potency of the formulation. Bioassay are the two types: in vitro and in vivo. In case of in vitro bioassays response of cells to hormones and growth factors is monitored. In case of in vivo bioassay pharmacological response of animal to proteins is monitored.

12. UV spectroscopy: Proteins containing aromatic amino acid residue as phenyl alanine , tyrosine can be detected by UV spectroscopy. It can be used as analytical determination methods. Bradford assay: In the presence of protein is an acidic medium, absorption maximum of coomassive brilliant blue G-250 dye changes. Lastly determination of concentration of the protein in the sample. Differential scanning calorimetry: DSC used as tools for investigating transition of conformation as a function temperature & more important the effect of potential stabilizing exciepient in a protein solutions . Chromatography: use to study stability of protein & peptides modes are : Normal phase HPLC Reversed phase HPLC Ion exchange chromatography

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