Porous microspheres - PrescottOChem

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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.

Advantages of Porous Microspheres

 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 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

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).

+ +

L-Lactide (L-LA) Glycolide (GA)

Polyethylene glycol (PEG)

Molecular weights of:

1000, 2000, 4000 o Seven different copolymers were synthesized using varied

PEG lengths and molar ratios of LA, GA, and PEG.

Preparation of porous microspheres

Double emulsion (W/O/W) combined with rapid solvent evaporation

Homogenized at 1500 rpm for 1hr

Then 500 rmp for 2hr at 40c

.02 g Evansblue

1 mL deionized water

.2 g PLGE dissolved in 6 mL dichloromethane (DCM)

200 mL 1% polyvinyl alcohol (PVA)

No pore forming agents! Controlled completely by composition of copolymers

To confirm PEG chains create porous structures only hydrophobic PLGA was used.

The effects of DCM were also tested.

(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.

These results suggest PEG and DCM effect the porous structure.

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.

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.

Effects of molar ratio of LA/GA

50/50, 70/30, 90/10

Same molecular weight

50/50 70/30 90/10

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.

Effects of polymer concentration

PLGE-2 with different concentrations

25mg/mL, 50mg/mL, 75mg/mL

25mg/mL 50mg/mL 75mg/mL

The size of the porous microspheres increased significantly when the concentration

Increased to 75m/mL.

Application of Microspheres

Drug delivery

Pulmonary drug delivery

Tissue regeneration

Transdermal patches

Arthritis treatment

Many More…

• 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

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.

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