Synthesis of Pan-bacterial Ceftaroline loaded into Electrospun Nano-fibrous Composite

Ceftaroline fosamil (brand name Teflaro, previously referred to as PPI-0903M, T-91825, TAK-599) is the fifth-generation broad-spectrum cephalosporin, which exhibits bactericidal activity against Gram-positive bacteria, including MRSA and MDRSP. Ceftaroline offers an exciting addition to the anti-MRS

Project Title

Synthesis of Pan-bacterial Ceftaroline loaded into Electrospun Nano-fibrous Composite

Project Area of Specialization

Wearables and Implantable

Project Summary

Ceftaroline fosamil (brand name Teflaro, previously referred to as PPI-0903M, T-91825, TAK-599) is the fifth-generation broad-spectrum cephalosporin, which exhibits bactericidal activity against Gram-positive bacteria, including MRSA and MDRSP. Ceftaroline offers an exciting addition to the anti-MRSA armamentarium, including activity against VISA, hVISA, VRSA, and daptomycin- and linezolid-resistant strains. Unique among many anti-MRSA agents, ceftaroline additionally provides activity against Gram-negative respiratory pathogens including H. influenzae and M. catarrhalis. But ceftaroline is not effective against organisms with AmpC ?-lactamases or extended?spectrum ??lactamase (ESBLs), such as Gram-negative bacteria and exhibits limited activity against most non-fermentative Gram-negative bacilli (e.g., Pseudomonas aeruginosa, Acinetobacter spp.) and many anaerobic species. The objective of the project is to prepare modified Ceftaroline by combining it with some ?-lactamase inhibitors that possesses potential activity against Gram-negative organisms such as Pseudomonas aeruginosa, Acinetobacter spp.

Project Objectives

1. Preparing Ceftaroline loaded electro-spun nanofibrous mesh.
2. Studying activity (MIC) of the prepared (in i) nanofibers against Gram-negative organisms such as Pseudomonas aeruginosa, Acinetobacter spp., as well as Gram-positive organisms.
3. Preparing electro-spun nanofibrous mesh of PET loaded with Ceftalorine / ?-lactamase inhibitors
4. Studying activity (MIC) of the prepared (in iii) nanofibers against Gram-negative organisms such as Pseudomonas aeruginosa, Acinetobacter spp., as well as Gram-positive organisms.

Project Implementation Method

Ceftaroline/?-lactamase loaded Zein nanofibers will be prepared using the procedure of Electrospinning. A solution of 25% (w/w) Zein in ethanol: water (4:1), Ceftaroline/?-lactamase will be added to polymer solution mixed at least for 4 h. The percentage of drug loading will be taken as 3%, 5%, 8% and 10% by weight of Zein. Electrospinning setup with a high-voltage power supply as a source of the electric field (can generate voltages up to 100 kV) shall be used. The polymer solution with drug will be delivered using a 5 ml plastic syringe having capillary tip with 0.6mm inner diameter and at an angle of 10° from the horizontal plane.The positive electrode will be connected a copper wire and dipped in to the polymer solution in syringe. The negative electrode will be grounded to a metallic drum(collector). The voltage shall be calibrated/ optimized between 10-13 kV. The Tip-to-Collector distance (TCD) shall be optimized between 12-12 cm. Electrospun Nanofibers (NF) shall be collected for 6 h over a rotatory metallic drum at room temperature (27?29 °C). The nanofiber film will be dried at room temperature to remove the residual solvent for a day before use. The prepared NF film shall be characterized using Scanning Electron Microscopy and FTIR (Fourier Transform Infrared) spectroscopy. The drug release profile shall be obtained by UV-VIS Spectrophotometry. Phosphate Buffered Saline(PBS) a universally accepted salt solution used in biological research shall be prepared by dissolving 8 g of NaCl, 0.2 g of KCl, 1.44 g of Na2HPO4, 0.24 g ofKH2PO4 in 1-liter distilled H2O. (average pH7.2?7.4) will be used as medium for drug release from Nano fibrous drug loaded film.
 

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Benefits of the Project

The high affinity of ceftaroline for penicillin-binding proteins is responsible for the potent activity observed against clinically relevant pathogens. With respect to the treatment of CABP, the activity of ceftaroline against pathogens such as S. pneumoniae, S. aureus, Haemophilus influenzae and Moraxella catarrhalis demonstrates coverage across a broad range of pathogens typically encountered in clinical practice. Ceftaroline is also very active against common pathogens seen in ABSSSIs such as S. aureus (methicillin-susceptible S. aureus and methicillin-resistant S. aureus) and Streptococcus pyogenes.

Technical Details of Final Deliverable

At the end of our project, we expect to have Ceftaroline/?-lactamase loaded Electrospun Nano-fibrous composite to inhibit of Gram positive and negative organisms. We shall provide benchmarking of our deliverable as a candidate for Modified fifth generation antibiotics that possesses potential activity against Gram-negative organisms such as Pseudomonas aeruginosa, Acinetobacter spp.

Final Deliverable of the Project

Hardware System

Core Industry

Health

Other Industries

Medical

Core Technology

Wearables and Implantables

Other Technologies

Others

Sustainable Development Goals

Good Health and Well-Being for People, Affordable and Clean Energy, Decent Work and Economic Growth

Required Resources

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