Densely PEGylated Polybenzofulvene Brushes for Potential Applications in Drug Encapsulation.

Marco Paolino,Claudia Bonechi,Mariano Licciardi,Daniele Piovani,Sandro Dattilo,Andrea Cappelli,Annalisa Reale,Alessandro Donati,Raniero Mendichi,Eugenio Paccagnini,Cinzia Scialabba,Federica Castriconi,Maurizio Canetti,Germano Giuliani,Giorgio Grisci,Gianluca Giorgi,Antonella Boccia,Filippo Samperi,Mariangela Gentile

doi:10.3390/pharmaceutics10040234

Abstract

The technique of grafting side chains onto a linear polymeric backbone is commonly used to confer to the new polymeric material with desired properties, such as tunable solubility, ionic charge, biocompatibility, or specific interactions with biological systems. In this paper, two new polybenzofulvene backbones were assembled by spontaneous polymerization of the appropriate benzofulvene monomers (4,6-PO-BF3k and 4’,6-PO-BF3k) bearing two clickable propargyloxy groups in different positions of the 3-phenylindene scaffold. Poly-4,6-PO-BF3k and poly-4’,6-PO-BF3k were grafted with monomethyl oligo(ethylene glycol) (MOEG) to prepare two new polybenzofulvene brushes (i.e., poly-4,6-MOEG-9-TM-BF3k and poly-4’,6-MOEG-9-TM-BF3k) by means of a “grafting onto” approach, that were characterized from the point of view of their macromolecular features, aggregation liability, and in a preliminary evaluation of biocompatibility. The obtained results make these PEGylated polybenzofulvene brushes (PPBFB) derivatives potentially useful as nanocarriers for nanoencapsulation and delivery of drug molecules.

Highlights

The dense grafting of polymeric side chains onto a linear polymeric backbone produces a unique class of macromolecules called molecular brushes, polymer brushes, or cylindrical brushes [1,2]
The technique of grafting side chains onto a linear polymeric backbone is commonly used to confer to the new polymeric material with desired properties, such as tunable solubility, ionic charge, biocompatibility, or specific interactions with biological systems
Poly-4,6-PO-BF3k and poly-4’,6-PO-BF3k were grafted with monomethyl oligo(ethylene glycol) (MOEG) to prepare two new polybenzofulvene brushes by means of a “grafting onto” approach, that were characterized from the point of view of their macromolecular features, aggregation liability, and in a preliminary evaluation of biocompatibility

Summary

Introduction

The dense grafting of polymeric side chains onto a linear polymeric backbone produces a unique class of macromolecules called molecular brushes, polymer brushes, or cylindrical brushes [1,2]. Structural features, such as side chain length, grafting density, and the physicochemical properties. Morreeoovveerr,,tthheeyymmaayybbee sensitivvee to the surrounding environment since their conformational behavior can bbeeaafffeecctteeddbbyysoslovlevnetnptrporpoeprteiretsi,etse,mtepmerpaetruarteu,rpeH, p, aHn,dainodniciosntricensgtrthen[g3]t.hT[h3e].syTnhtheessyisnothf ebsriussohfblirkuesahr-clihkieteacrtuchreitsectaunrebse cpaenrfboermpedrfobrymmedeabnys omf etahnreseodf itfhferreeendt iafpfeprreonatcahpepsr[o3a]:c(hae)sg[r3a]f:ti(nag) gthraroftuinggh t(hGrTo,ugphol(yGmT,epriozlaytmioenriozaf timonacorfomaocnromeornso)m[4e,r5s]); [4(b,5)];g(rba)fgtirnagftionngton(tGo O(G,Oa,daddidtiiotinontotoaa polymeric backkbboonnee off separatteellyy preeppaarreedd ssiiddee cchhaaiinnss)) [[66]];; and (c) grafting from (polymeerriizzaattiioonn ooff side chains froomm aa mmaaccrrooiinniittiiaattoorr bbaacckkbboonnee)) [[77,,88]]. BByy ccoommbbiinniinngg ddiiffffeerreenntt ssyynntthheetticic sstrtraateteggieies,s,wwe ededseisgingendedanadndsysnythnethsiezseizdeda laarlgaergfeamfailmy iloyf opfolpyomlyemr berrubsrhuessh(eFsig(Fuirgeu1r)e o1b)taoibnteadinbeyd gbryafgtirnagftimngonmomoneothmyeltohlyigl oo(leigthoy(eletnheylgelnyecogll)y(cMolO) E(MGO) sEiGde) scihdaeinsch(aSiCn)s o(nStCo)thoenptoolythbeenzpoofluylbveennzeobfualcvkebnoeneboafckpboolyn-eBFo1f apnodlyp-oBlFy1-BFa3nkd. Tphoilsy-nBeFw3kf.amilTyhoisf nPeEwGyflaamteidlypooflyPbEeGnzyolafutelvdenpeolbyrbuesnhzeosfu(PlvPeBnFeB)brinucslhuedses(PpPoBlyF-B2)-MinOclEuGd-e9s-BpFo1ly[-225-M], pOoElyG--69--MBOF1EG[2-59]-, pBoFl3yk-6[-2M6]O, aEnGd-9p-oBlFy3-k6-M[26O],EaGn-d9-pToMly--B6F-M3kO(ETGM-9=-TtrMia-zBoFlo3km(eTtMhy=l stpraiaczeor)lo[2m7,e2t8h]y. Tphoilsy-nBeFw3kf.amilTyhoisf nPeEwGyflaamteidlypooflyPbEeGnzyolafutelvdenpeolbyrbuesnhzeosfu(PlvPeBnFeB)brinucslhuedses(PpPoBlyF-B2)-MinOclEuGd-e9s-BpFo1ly[-225-M], pOoElyG--69--MBOF1EG[2-59]-, pBoFl3yk-6[-2M6]O, aEnGd-9p-oBlFy3-k6-M[26O],EaGn-d9-pToMly--B6F-M3kO(ETGM-9=-TtrMia-zBoFlo3km(eTtMhy=l stpraiaczeor)lo[2m7,e2t8h]y. l spacer) [27,28]

Methods

Results

Conclusion