Biodegradeable Polyester Particles For Encapsulation – Polylactic Acid

Many advanced drug delivery systems have started using biodegradeable polyesters. These materials are based on matrices of poly(ε‐caprolactone) (PCL), poly(lactic acid) (PLA) and poly(lactic‐co‐glycolic acid) (PLGA) (Mathiowitz et al., 1997).

Polylactic acid is certainly a very suitable alternative to many petrochemical based plastics. It in particular can be produced from renewable resources as well as being biodegradeable. It decomposes to water, carbon dioxide gas and humus which is soil material. It is regularly used in films, paper coatings, fibers and packaging (Drumright et al., 2000). The polymer has been valued for surgical sutures which are self-dissolving and then eliminated from the body (Wise et al., 1979)

The polyesters are ideal for drug applications because they have low if any immunogenicity and certainly toxicity (Reed et al., 1981). It is worth noting there are many other biodegradeable polymers such as the poly(orthoesters) (POE), poly(anhydrides), poly(amides), poly(ester amides), poly(phosphor esters), hyaluronic acid and chitosan (Kamaly et al., 2016).

It s possible to combine polylactic acid with glycolic acid so that high molecular weight proteins can be delivered (Cohen et al., 1991). Proteins such as bovine serum albumin (BSA) have been incorporated into polylactic acid with a multibranched polyglycerol (HPG) (Gao et al., 2010). The composites have high strength, hydrophobicity and are pliable like plastic and can be moulded into shapes.

From the drug-delivery point of view, most of the encapsulated drugs are low molecular weight steroids for contraception and other small peptides. Polymer degradation is part of the drug release mechanism in the body.

Method Of Preparation Of Polylactic acid/Glycolic Acid (PLGA) Microcapsules

Microspheres are usually prepared as a copolymer ratio of 75/25. The molecular weight is 14 kDal or less. The method is a modified solvent evaporation technique using either a single emulsion or a double emulsion technique.

In a typical method, protein for example is dissolved in pure water and then mixed with PLGA in methylene chloride as a solvent. The whole mixture is rapidly mixed either by vortex or sonication to generate the first emulsion – the inner emulsion. This emulsion is then poured into an aqueous solution of 1% PVA (polyvinylalcohol) which is saturated with methylene chloride to form the second emulsion or outer emulsion with vigorous mixing. The polyvinylalcohol acts as a surfactant. The double emulsion is then poured into aqueous 0.1% PVA  (polyvinylalcohol) and stirred until all the methylene chloride evaporates off to leave solid microspheres.

An alternative surfactant would be D-alpha-tocpheryl polyethylene glycol 1000 succinate (vitamin E TPGS) which is better for drug loading than using PVA (5mg/ml) (Feng et al., 2007).

Centrifugation is used to collect the microspheres and then sized with sieves with apertures of 100 microns before freeze-drying.

Coacervation is another method of preparation which depends on liquid-liquid separation techniques.

Curcumin And Polylactic Acid Encapsulation

Curcumin for example has been encapsulated in a polylactic acid-based nanoparticle. Curcumin is not only a nutrient, an antioxidant, it is also an antibacterial agent and capable of killing yeasts and algae.

The nanoparticles were synthesized using a nanoprecipitation method (Kumari et al., 2010). In one set, these nanoparticles had a negative or anionic charge with a maximum concentration of 260 micromolar curcumin.

 The method here, was to make a curcumin stock solution (4mg/ml) in acetone. Another solution, an aqueous phase containing dextran sulphate (DEX) in ultrapure sterile water was dropped slowly into a polylactic acid (0.5% in acetone) and the organic phase containing the curcumin (i.e. acetone) with gentle stirring. The whole polymer/organic phase mix was left to stand for 24 hours so that all acetone evaporated away.

To prepare a cationic or positively charged polylactic nanoparticle, cetyltrimethylammonium bromide (CTAB) (2% w/v) was prepared in ultrapure sterile water with sodium chloride (1.76%w/v) added to act as a surfactant after completely evaporating away the solvent.

The Release of The Drugs From Polylactic Acid

Release of any encapsulated drug or flavour depends on diffusion and bulk erosion of the biopolymer (kamaly et al., 2016). Diffusion rate depends on the encapsulated materials level of diffusivity and partition coefficient into the surrounding medium. The more water soluble the compound the more rapid the release. Hydrophobic materials that are encapsulated actually hinder water diffusion into any microparticle and reduce the rate of polymer degradation (Klose et al., 2008).

References

Cohen, S., Yoshioka, T., Lucarelli, M., Hwang, L. H., & Langer, R. (1991). Controlled delivery systems for proteins based on poly (lactic/glycolic acid) microspheres. Pharmaceutical Research, 8(6), pp.  713-720. Article

Drumright, R. E., Gruber, P. R., & Henton, D. E. (2000). Polylactic acid technology. Advanced Materials, 12(23), pp. 1841-1846 Article  

Feng, S.-S., Zeng, W., Teng Lim, Y., Zhao, L., Yin Win, K., Oakley, R., et al. (2007). Vitamin E TPGS-emulsified poly(lactic-co-glycolic acid) nanoparticles for cardiovascular restenosis treatment. Nanomedicine (Lond.) 2, pp. 333–344. Article 

Gao, X., Zhang, X., Zhang, X. et al. Polym. Bull. (2010) 65: 787. Article  

Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016). Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chemical Reviews, 116(4), pp. 2602-2663

Klose, D., Siepmann, F., Elkhamz, K., and Siepmann, J. (2008). PLGA-based drug delivery systems: importance of the type of drug and device geometry. Int. J. Pharm. 354, pp. 95–103. Article 

Klose, D., Siepmann, F., Elkharraz, K., Krenzlin, S., and Siepmann, J. (2006). How porosity and size affect the drug release mechanisms from PLGA-based microparticles. Int. J. Pharm. 314, pp. 198–206. Article 

Kumari, A., Yadav, S.K., Yadav, S.C. (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B Biointerfaces. 75 pp. 1–18. Article pmid:1978254 

Makadia, H. K., & Siegel, S. J. (2011). Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers, 3(3), pp. 1377-1397. Article  

Mathiowitz, E., Jacob, J.S., Jong, Y.S., Carino, G.P., Chickering, D.E., Chaturvedi, P., Santos, C.A., Vijayaraghavan, K., Montgomery, S., Bassett, M., and Morrell, C. (1997) Biologically erodable microspheres as potential oral drug delivery systems. Nature. 386: pp. 410–414 Article  

Reed, A.M. and Gilding, D.K. (1981) Biodegradable polymers for use in surgery—Poly(glycolic)‐poly(lactic acid) Homo and co‐polymers .2. Invitro Degradation. Polymer. 22: pp. 494–498 Article 

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