Protein peptide drug delivery system.pptx

Protein peptide drug delivery system

1. PROTEIN PEPTIDE DRUG DELIVERY SYSTEM Presented by  V. Sravani © Sravani V

2. What is Protein peptide drug delivery system Why do we need to develop new delivery systems to deliver proteins  What are the barriers in administration through different routes except parenteral What are the strategies  in delivering proteins and peptides through oral and transdermal route. Recent advancements  What is the current global market size 

3. 2021

4. Classification of therapeutic proteins with marketed formulations Monoclonal Antibodies ( mAbs ) : Trastuzumab  Herceptin, Perjeta Cytokines : Interferon-alpha  Roferon -A, Intron A Enzymes : Alteplase (tissue plasminogen activator) Activase , Actilyse Hormones : Insulin (recombinant human insulin) Humulin, Novolin Growth Factors : Erythropoietin (EPO)  Epogen, Procrit Vaccines : Recombinant Hepatitis B vaccine    Engerix -B, Recombivax HB.  Fusion Proteins : Etanercept (TNF-alpha inhibitor) Enbrel Antibody-drug Conjugates (ADCs) : Brentuximab vedotin Adcetris Thrombolytics : Reteplase ,  Retavase Blood Factors : Factor VIII (recombinant)  Advate , Kogenate Interleukins  : Aldesleukin (IL-2)  Proleukin Interferons : Interferon-beta, Avonex, Betaseron

5. Barriers in Oral delivery Degradation by gastrointestinal proteases Low permeability of intestinal epithelium First pass metabolism Immunogenicity Larger molecular size , low lipophilicity  charged functional groups    These characteristics lead to the low bioavailability of most orally administered peptides (<2%) and short half-lives (<30 min)

6. Strategies for oral delivery of peptides Direct structural modification       Cyclization  Cyclosporine- cyclic peptide is resistant to proteolytic degradation and also has higher than expected absorption after oral administration Other proteins : somatostatin and encephalin     PEGylation Improved protein absorption and systemic stability,  Insulin PEGylated with a 750 Da version of PEG formulated into a mucoadhesive tablet (observed drop in blood glucose levels of approximately 50% 3 h after administration) PEGylation of salmon calcitonin ( sCT ), resulted in resistance to intestinal enzymes nearly sixfold increase in intestinal absorption and slowed systemic clearance compared with the unmodified version of sCT  

7. Protein  lipidization   Fatty conjugates of proteins demonstrate improved transport across biological membranes, higher stability and longer plasma half-lives.  Caprates, medium-chain fatty acids, promote paracellular diffusion of Class III (highly soluble, low permeability) molecules such as peptides. Triglycerides can be used to evade first-pass metabolism.  Enzyme inhibitors   Aprotinin ( Trasylol ™)  - soybean trypsin inhibitor (reduce bleeding during complex surgeries) When co administered with insulin to rats and dogs, levels of immunoreactive insulin rose proportionally to a decrease in blood glucose levels. Blood glucose decreased by 30% over the next 3 h compared with administration of insulin alone

8. Gastrointestinal mucoadhesive patch system The system contains four layered films in an enteric capsule. Layer one is the backing layer, layer two is the middle or drug layer, layer three is the adhesive layer, and layer four is the surface layer. 

9. Absorption enhancers                                                                     Chitosans  - enhance the absorption of molecules such as atenolol, insulin and 8-R-vasopressin In vivo studies with  chitosans  demonstrated a threefold increase in octreotide absorption when the two were co administered into the duodenum  medium-chain fatty acids (caprylate, caprate and laurate) - enhance paracellular permeability of hydrophilic compounds. Toxins- Zonula  occludens  toxin (ZOT)vibrio cholerae- increase the permeability of small intestine mucosa by reversibly affecting the structure of TJs.  coadministration of cell-penetrating peptides

10. Hydrophilic mucoadhesive polymer -polyacrylates, cellulose, chitosan Thiomers  - thiolated  polymers  Nano emulsions   Do not cream, flocculate, coalesce or sediment Self-nanoemulsifying drug-delivery system,’ or SNEDDS – A significant increase in SNEDD – BLM absorption compared with free BLM  fluorescein isothiocyanate-labeled β-lactamase increase transport of fluorescein isothiocyanate–bleomycin across MDCK monolayer of cells Hydrogels  Nano particles – lipid based, Polymeric and Inorganic (gold, silica, magnetic ) Microspheres and Microcapsules – polymeric microspheres and  protein loaded micro capsules Emisphere's  Eligen ™ system (NY, USA), which has the potential to deliver therapeutics from 0.5–150  kDa . The drug–carrier system known as SNAC (n-(8-[2-hydroxylbenzoyl]amino)caprylic acid) can be used to orally deliver active peptides into circulation Carrier systems 

11. Strategies for Transdermal delivery of Proteins and peptides Microneedle technology  Thermal ablation  Electroporation Sonophoresis Iontophoresis Biochemical enhancement

12. Micro needle technology  small needles made of silicon, polymers that create small pores in the skin  Zosano Pharma (CA, USA), who have developed a patch containing drug-coated microneedles capable of delivering a variety of drugs including peptides and vaccines Thermal ablation short pulses of high heat (approximately 100°C) to create small, reversible channels in the micron size range PassPort ® (Nitto Denko [Osaka, Japan])  ViaDor ® (Syneron Medical Ltd [ Yokneam , Israel]

13. Electroporation  very short pulses of high voltages (between 10 and 100 V) to perforate the skin. multiple DNA-based vaccines are in clinical trials, which, if successful, could pave the way for peptide-based vaccines Sonophoresis Cavitational ultrasound, relies on the application of sound waves to the skin to increase its permeability delivery of insulin for Type I diabetes using the sonophoretic U-Strip system (Transdermal Specialties, Inc. [PA, USA]) is presently in clinical trials

14. Iontophoresis Uses principles of both electro repulsion (for charged peptides) and electroosmosis (for uncharged peptides) to act on the drug molecules themselves rather than the skin lidocaine ( LidoSite ®, Vyteris [NV, USA]) Delivery of gonadotropin releasing hormone and insulin, has reached clinical trials  Biochemical enhancement Early stages of development Magainin known to form pores in bacterial cell membranes, demonstrated to increase the permeability of small molecules.

15. Current research landscape  Antiviral peptides ( myrcludex B against HBV and HDV423–425, flufirvitide against Influenza virus426,427, and sifuvirtide against HIV-1) Peptides for the treatment of 

16. Emerging Technologies In The Delivery Of Proteins & Peptides Electrohydrodynamic Processes (Electrospinning & Electrospraying ) Microfluidics & Nano fluidics Microelectromechanical Systems (MEMS & BioMEMS) Additive Manufacturing (3D Printing & Bioprinting)

17. References Kalluri H, Banga AK. Transdermal delivery of proteins. AAPS PharmSciTech . 2011 Mar;12(1):431-41. doi : 10.1208/s12249-011-9601-6. Epub 2011 Mar 3. PMID: 21369712; PMCID: PMC3066337 Thoa Thi Kim Nguyen, Khang-Yen Pham, Simmyung Yook,Engineered therapeutic proteins for sustained-release drug delivery systems, Acta Biomaterialia , Volume 171,2023, Pages 131-154 Wang, L., Wang, N., Zhang, W.  et al.  Therapeutic peptides: current applications and future directions.  Sig Transduct Target Ther   7 , 48 (2022). Emerging Technologies In The Delivery Of Proteins & Peptides, Dimitrios A. Lamprou, Queen’s University Belfast Recent Advances in Protein and Peptide Drug Delivery: A  Special Emphasis on Polymeric Nanoparticles, Ashaben Patel#, Mitesh Patel#, Xiaoyan Yang, and Ashim K. Mitra* Protein Pept Lett. 2014 ; 21(11): 1102–1120.

18. Thank you