Applicability of electrospun polypropylene carbonate polymers as a drug carrier for sirolimus

Sun,Hourong; Gu,Xinghua; Liu,Kai; Fang,Changcun; Tang,Mengmeng

doi:10.3892/mmr.2017.6540

Applicability of electrospun polypropylene carbonate polymers as a drug carrier for sirolimus

Authors:
- Hourong Sun
- Xinghua Gu
- Kai Liu
- Changcun Fang
- Mengmeng Tang
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Affiliations: Department of Cardiovascular Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: May 2, 2017 https://doi.org/10.3892/mmr.2017.6540
Pages: 4253-4258

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Abstract

Polypropylene carbonate (PPC), a biodegradable aliphatic polyester, exhibits one particular advantage over other polyesters, which is that following degradation in vivo, it primarily produces H2O and CO2, causing minimal side effects. Although PPC exhibits limited mechanical strength, and is therefore not able to serve as a scaffold to support tissue regeneration, it may be suitable for drug delivery; however, this requires further investigation. In the present study, electrospinning was applied to generate PPC polymers containing sirolimus, a cell growth‑inhibiting drug which is used to treat restenosis. The properties of PPC‑sirolimus polymers were examined using scanning electron microscopy, differential scanning calorimetry and in vitro degradation assays. Drug loading and entrapment efficiency were determined, and in vitro sirolimus‑release from the polymer was assessed. Furthermore, the effect of PPC‑sirolimus polymers on cell growth was measured using an MTT assay in vitro. The results of the present study demonstrated that electrospun PPC polymers formed a uniform three‑dimensional, grid‑intertwined, net‑like structure; the surface of the polymers was smooth and the diameter was ~3 µm. Differential scanning calorimetry analysis demonstrated that sirolimus existed in an amorphous state in the polymer. Following soaking in PBS for 4 weeks, the polymer swelled and the net‑like structure broke down and fragmented. Sirolimus loading and entrapment efficiency were 10.3±3.2 and 95.1±10.6%, respectively. Sirolimus‑release from PPC‑sirolimus polymers continued for 28 days in PBS. PPC‑sirolimus markedly inhibited the growth of rat aortic adventitial fibroblast cells, an effect which was not observed with PPC alone. The results of the present study suggest that PPC polymers are a promising alternative drug carrier for sirolimus.

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1	Lendlein A: Polymers in biomedicine. Macromol Biosci. 10:993–997. 2010. View Article : Google Scholar
2	Chattopadhyay S and Raines RT: Review collagen-based biomaterials for wound healing. Biopolymers. 101:821–833. 2014. View Article : Google Scholar :
3	Williams CK: Synthesis of functionalized biodegradable polyesters. Chem Soc Rev. 36:1573–1580. 2007. View Article : Google Scholar
4	Gunatillake P, Mayadunne R and Adhikari R: Recent developments in biodegradable synthetic polymers. Biotechnol Annu Rev. 12:301–347. 2006. View Article : Google Scholar
5	Fambri L, Pegoretti A, Fenner R, Incardona SD and Migliaresi C: Biodegradable fibres of poly(L-lactic acid) produced by melt spinning. Polymer. 38:79–85. 1997. View Article : Google Scholar
6	Peyton SR, Raub CB, Keschrumrus VP and Putnam AJ: The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells. Biomaterials. 27:4881–4893. 2006. View Article : Google Scholar
7	Kapoor DN, Bhatia A, Kaur R, Sharma R, Kaur G and Dhawan S: PLGA: A unique polymer for drug delivery. Ther Deliv. 6:41–58. 2015. View Article : Google Scholar
8	Langer RS and Peppas NA: Present and future applications of biomaterials in controlled drug delivery systems. Biomaterials. 2:201–214. 1981. View Article : Google Scholar
9	Middleton JC and Tipton AJ: Synthetic biodegradable polymers as orthopedic devices. Biomaterials. 21:2335–2346. 2000. View Article : Google Scholar
10	Seyednejad H, Ghassemi AH, Van Nostrum CF, Vermonden T and Hennink WE: Functional aliphatic polyesters for biomedical and pharmaceutical applications. J Control Release. 152:168–176. 2011. View Article : Google Scholar
11	Cameron DJ and Shaver MP: Aliphatic polyester polymer stars: Synthesis, properties and applications in biomedicine and nanotechnology. Chem Soc Rev. 40:1761–1776. 2011. View Article : Google Scholar
12	Jain R, Shah NH, Malick AW and Rhodes CT: Controlled drug delivery by biodegradable poly(ester) devices: Different preparative approaches. Drug Dev Ind Pharm. 24:703–727. 1998. View Article : Google Scholar
13	Li XH, Meng YZ, Chen GQ and Li RKY: Thermal properties and rheological behavior of biodegradable aliphatic polycarbonate derived from carbon dioxide and propylene oxide. J Appl Polym Sci. 94:711–716. 2004. View Article : Google Scholar
14	Zhong X and Dehghani F: Solvent free synthesis of organometallic catalysts for the copolymerisation of carbon dioxide and propylene oxide. Appl Catal B. 98:101–111. 2010. View Article : Google Scholar
15	Li WJ, Laurencin CT, Caterson EJ, Tuan RS and Ko FK: Electrospun nanofibrous structure: A novel scaffold for tissue engineering. J Biomed Mater Res. 60:613–621. 2002. View Article : Google Scholar
16	Ji Y, Ghosh K, Shu XZ, Li B, Sokolov JC, Prestwich GD, Clark RA and Rafailovich MH: Electrospun three dimensional hyaluronic acid nanofibrous scaffolds. Biomaterials. 27:3782–3792. 2006. View Article : Google Scholar
17	Tipduangta P, Belton P, Fábián L, Wang LY, Tang H, Eddleston M and Qi S: Electrospun polymer blend nanofibers for tunable drug delivery: The role of transformative phase separation on controlling the release rate. Mol Pharm. 13:25–39. 2016. View Article : Google Scholar
18	Zheng L, Chen J, Ma Z, Liu W, Yang F, Yang Z, Wang K, Wang X, He D, Li L and Zeng J: Capsaicin enhances anti-proliferation efficacy of pirarubicin via activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells. Mol Med Rep. 13:881–887. 2016.
19	Zeng J, Chen X, Xu X, Liang Q, Bian X, Yang L and Jing X: Ultrafine fibers electrospun from biodegradable polymers. J Appl Polym Sci. 89:1085–1092. 2003. View Article : Google Scholar
20	Ni S, Xia T, Li X, Zhu X, Qi H, Huang S and Wang J: Sustained delivery of chondroitinase ABC by poly(propylene carbonate)-chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection. Brain Res. 1624:469–478. 2015. View Article : Google Scholar
21	Zou W, Cao G, Xi Y and Zhang N: New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles. Drug Deliv. 16:15–23. 2009. View Article : Google Scholar
22	Gu M and Brecher P: Nitric oxide-induced increase in p21(Sdi1/Cip1/Waf1) expression during the cell cycle in aortic adventitial fibroblasts. Arterioscler Thromb Vasc Biol. 20:27–34. 2000. View Article : Google Scholar
23	Tsuruda T, Kato J, Cao YN, Hatakeyama K, Masuyama H, Imamura T, Kitamura K, Asada Y and Eto T: Adrenomedullin induces matrix metalloproteinase-2 activity in rat aortic adventitial fibroblasts. Biochem Biophys Res Commun. 325:80–84. 2004. View Article : Google Scholar
24	Duncan R: Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer. 6:688–701. 2006. View Article : Google Scholar
25	Davis ME, Chen Z and Shin DM: Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat Rev Drug Discov. 7:771–782. 2008. View Article : Google Scholar
26	Liechty WB, Kryscio DR, Slaughter BV and Peppas NA: Polymers for drug delivery systems. Annu Rev Chem Biomol Eng. 1:149–173. 2010. View Article : Google Scholar :
27	Merkle HP: Drug delivery's quest for polymers: Where are the frontiers? Eur J Pharm Biopharm. 97:293–303. 2015. View Article : Google Scholar
28	Fu K, Pack DW, Klibanov AM and Langer R: Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres. Pharm Res. 17:100–106. 2000. View Article : Google Scholar
29	Danmark S, Finne-Wistrand A, Schander K, Hakkarainen M, Arvidson K, Mustafa K and Albertsson AC: In vitro and in vivo degradation profile of aliphatic polyesters subjected to electron beam sterilization. Acta Biomater. 7:2035–2046. 2011. View Article : Google Scholar
30	Ding AG and Schwendeman S: Acidic microclimate pH distribution in PLGA microspheres monitored by confocal laser scanning microscopy. Pharm Res. 25:2041–2052. 2008. View Article : Google Scholar :
31	Zamani M, Prabhakaran MP and Ramakrishna S: Advances in drug delivery via electrospun and electrosprayed nanomaterials. Int J Nanomedicine. 8:2997–3017. 2013.
32	Zahedi P and Lee PI: Solid molecular dispersions of poorly water-soluble drugs in poly(2-hydroxyethyl methacrylate) hydrogels. Eur J Pharm Biopharm. 65:320–328. 2007. View Article : Google Scholar
33	Kang GD, Cheon SH and Song SC: Controlled release of doxorubicin from thermosensitive poly(organophosphazene) hydrogels. Int J Pharm. 319:29–36. 2006. View Article : Google Scholar