1. Abstract Polymeric Porous microspheres are an effective drug delivery mechanism able to control drug release, preventing drug wastage and lowering costs. A review of the current state of research in the area of porous microspheres indicates microsphere size, pore size, pore distribution and drug loading efficiency can be controlled by polymer composition. Evansblue loaded Porous microspheres were prepared using double emulsion technique combined with rapid solvent evaporation. The effects of hydrophilic PEG chain length, molar ratio of L-LA/GA, and polymer concentration were examined. The results suggest PEG and DCM are responsible for the porous structure. The molar ratio of L-LA/GA and polymer concentration also play a role in porous microsphere formation.

2.  Small material (50-200nm) that has a high surface area. More able to interact with environment.  Biodegradable. Safely degenerate by surface erosion. Important feature when toxic drug is present.  Pores can be loaded with drugs. Advantages of Porous Microspheres

3. Advantages of Pores  The size of the channel can change the release kinetics. If the channel size is similar to the size of the drug molecule being released only one molecule will be released at a time. The drug release will allow a therapeutic range to be consistently reached preventing drug wastage and lowering costs

6. L-Lactide (L-LA) + + Glycolide (GA) Polyethylene glycol (PEG) Molecular weights of: 1000, 2000, 4000 Procedure o Amphiphilic triblock copolymer poly(lactide-co-glycolide-b- ethylene glycol-b-lactide-co-glycolide) (PLGE) were synthesized by a ring opening polymerization of lactate (LA) and glycol (GA) in the presence of polyethylene glycol (PEG). o Seven different copolymers were synthesized using varied PEG lengths and molar ratios of LA, GA, and PEG.

8. Preparation of porous microspheres.2 g PLGE dissolved in 6 mL dichloromethane (DCM).02 g Evansblue 1 mL deionized water 200 mL 1% polyvinyl alcohol (PVA) Homogenized at 1500 rpm for 1hr Then 500 rmp for 2hr at 40c No pore forming agents! Controlled completely by composition of copolymers Double emulsion (W/O/W) combined with rapid solvent evaporation

9. (A) SEM images of PLGA microspheres prepared by a modified double emulsion (W/O/W)-solvent evaporation technique; (B) SEM images of PLGE porous microspheres prepared by increasing the volume of DCM to 1.5 times. To confirm PEG chains create porous structures only hydrophobic PLGA was used. The effects of DCM were also tested. These results suggest PEG and DCM effect the porous structure.

10. Does temperature effect formation of porous microspheres? When prepared at 40c and room temperature the porous microspheres prepared At 40c had double drug encapsulation efficiency then when prepared at room temperature.

11. Effects of varied hydrophilic PEG length PLGE-2, PLGE-5, PLGE-7 Same molecular weight PLGE-2 PEG=1000 PLGE-5 PEG=2000 PLGE-7 PEG=4000 With increase PEG length microspheres evolved irregularly with wrinkly surfaces.

12. Effects of molar ratio of LA/GA 50/50, 70/30, 90/10 Same molecular weight 50/5070/3090/10 When the molar ratio was 50/50 the microspheres were irregular and wrinkly. As the molar ratio of LA increased the microspheres were spherical and pore dense.

13. Effects of polymer concentration PLGE-2 with different concentrations 25mg/mL, 50mg/mL, 75mg/mL 25mg/mL50mg/mL75mg/mL The size of the porous microspheres increased significantly when the concentration Increased to 75m/mL.

14. Application of Microspheres Drug delivery Pulmonary drug delivery Tissue regeneration Transdermal patches Arthritis treatment Many More…

15. Prevention - Microspheres prevent drug wastage! Design for degradation - Microspheres are biodegradable! Safer solvents and auxiliaries - No pore forming agents were used in the making of the microspheres

16. Sources Anderson, J., & Shive, M. (2012). Biodegradation and biocompatibility of PLA and PLGA microspheres. Advanced Drug Delivery Reviews, 64, 72-82. Fan, J., Song, Y., Wang, S., Jiang, L., Zhu, M., & Guo, X. (2013). A synergy effect between the hydrophilic PEG and rapid solvent evaporation induced formation of tunable porous microspheres from a triblock copolymer. Royal Society of Chemistry, (2), 629-633. Giri, T., Choudhary, C., Alexander, A., Badwaik, H., & Tripathi, D. (2013). Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery. Saudi Pharmaceutical Journal, 21(2), 125-141. Zhang, M., Yang, Z., Chow, L., & Wang, C. (2003). Simulation of drug release from biodegradable polymeric microspheres with bulk and surface erosions. Journal of Pharmaceutical Sciences J. Pharm. Sci., 56, 2040-2056.