Surface-functionalized diatom microcapsules for drug delivery of water-insoluble drugs

Abstract

Naturally available and biocompatible materials are potential substitutes for synthetic mesoporous materials as suitable drug carriers for the development of cost-effective drug delivery systems. This work investigates the application of a porous silica material derived from diatoms, also known as diatomaceous earth. The aim is to explore the surface functionalization of diatom microcapsules and their impact on the drug loading and release characteristics of water-insoluble drugs. Indomethacin was used as the model for poorly soluble drug. The surface modification on diatoms was performed with two organosilanes; 3-aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene diamine and phosphonic acids (2-carboxyethyl-phosphonic acid and 16-phosphono-hexadecanoic acid) providing organic surface hydrophilic and hydrophobic properties. Extensive characterizations using scanning electron microscopy, X-ray photoelectron spectroscopy and differential scanning calorimetry was performed to confirm covalent grafting of monolayer aminosilane and phosphonic acid on the diatom surfaces. Differences in loading capacity of diatoms (15–24%) and release time (6–15 days) were observed which is due to the presence of different functional groups on the surface. It was found that 2-carboxyethyl-phosphonic acid, 3-aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene diamine render diatom surfaces hydrophilic, due to polar carboxyl functional group (COOH) and active amine species (NH and NH₂) that favor drug adsorption; better encapsulation efficiency and prolonged release of drugs, over the hydrophobic surface created by 16-phosphono-hexadecanoic acid. This work demonstrates diatom porous silica as a promising drug carrier, with possibility to further improve their performances by tailoring their surface functionalities to achieve the required drug loading and release characteristics for different therapeutic conditions.

Keywords

Drug delivery diatoms diatomaceous earth surface modifications silanes phosphonic acid indomethacin

Get full access to this article

View all access options for this article.

References

Drews

. Drug discovery: a historical perspective. Science 2000; 287: 1960–1964.

Fahr

Liu

. Drug delivery strategies for poorly water-soluble drugs. Exp Opin Drug Deliv 2007; 4: 403–416.

El-Aneed

. An overview of current delivery systems in cancer gene therapy. J Control Release 2004; 94: 1–14.

Van

McGuire

Langer

. Small scale systems for in vivo drug delivery. Nature Biotechnol 2003; 21: 1184–1191.

Slowing

Trewyn

Giri

. Mesoporous silica nanoparticles for drug delivery and biosensing applications. Adv Funct Mater 2007; 17(8): 1225–1236.

Vallet-Regí

Balas

Arcos

. Mesoporous materials for drug delivery. Angew Chem Int Ed 2007; 46(40): 7548–7558.

Simovic

Eskandar

Sinn Aw

. Silica materials in drug delivery applications. Curr Drug Discov Technol 2011; 8(3): 250–268.

Losic

Simovic

. Self ordered nanopore and nanotube platforms for drug delivery applications. Expert Opin Drug Deliv 2009; 6(12): 1363–1381.

Vallet-Regí

Ruiz-Gonzalez

Izquierdo-Barba

. Revisiting silica based ordered mesoporous materials: medical applications. J Mater Chem 2006; 16(1): 26–31.

10.

Sarikaya

. Biomimetics: materials fabrication through biology. Proc Natl Acad Sci USA 1999; 96(25): 14183–14185.

11.

Morse

. Silicon biotechnology: harnessing biological silica production to construct new materials. Trends Biotechnol 1999; 17(6): 230–232.

12.

Sumper

Brunner

. Learning from diatoms: nature’s tools for the production of nanostructured silica. Adv Funct Mater 2006; 16(1): 17–26.

13.

Gordon

Losic

Tiffany

. The glass menagerie: diatoms for novel applications in nanotechnology. Trends Biotechnol 2009; 27(2): 116–127.

14.

Parkinson

Gordon

. Beyond micromachining: the potential of diatoms. Trends Biotechnol 1999; 17(5): 190–196.

15.

Lopez

Desclés

Allen

. Prospects in diatom research. Curr Opin Biotechnol 2005; 16(2): 180–186.

16.

Losic

Mitchell

Voelcker

. Diatomaceous lessons in nanotechnology and advanced materials. Adv Mater 2009; 21(29): 2947–2958.

17.

Fuhrmann

Landwehr

El Rharbi-Kucki

. Diatoms as living photonic crystals. Appl Phys B: Lasers Opt 2004; 78(3): 257–260.

18.

Losic

Rosengarten

Mitchell

. Pore architecture of diatom frustules: potential nanostructured membranes for molecular and particle separations. J Nanosci Nanotechnol 2006; 6(4): 982–989.

19.

Lettieri

Setaro

De Stefano

. The gas-detection properties of light-emitting diatoms. Adv Funct Mater 2008; 18(8): 1257–1264.

20.

Parker

Townley

. Biomimetics of photonic nanostructures. Nat Nanotechnol 2007; 2(6): 347–353.

21.

Losic

Triani

Evans

. Controlled pore structure modification of diatoms by atomic layer deposition of TiO2. J Chem Mater 2006; 16: 4029–4034.

22.

Losic

Mitchell

Lal

. Rapid fabrication of micro- and nanoscale patterns by replica molding from diatom biosilica. Adv Funct Mater 2007; 17(14): 2439–2446.

23.

Losic

Short

Mitchell

. AFM nanoindentations of diatom biosilica surfaces. Langmuir 2007; 23(9): 5014–5021.

24.

Losic

Mitchell

Voelcker

. Fabrication of gold nanostructures by templating from porous diatom frustules. New J Chem 2006; 30: 908–914.

25.

Yang

Lopez

Rosengarten

. Diatoms: self-assembled silica nanostructures, and templates for bio/chemical sensors and biomimetic membranes. Analyst 2011; 136: 42–53.

26.

Simovic

Addai-Mensah

. Silica microcapsules from diatoms as new carrier for delivery of therapeutics. Nanomedicine 2011; 6(7): 1159–1173.

27.

Aw MS, Simovic S, Yu Y, et al. Porous silica microshells from diatoms as biocarrier for drug delivery applications. Powder Technol. Doi: 10.1016/j.powtec.2011.04.023.

28.

Losic

. Surface functionalization of diatoms with dopamine modified iron oxide nanoparticles: toward magnetically guided drug microcarriers with biologically derived morphologies. Chem Commun 2010; 46: 6323–6325.

29.

Wang

. A novel hierarchical nanozeolite composite as sorbent for protein separation in immobilized metal-ion affinity chromatography. Adv Mater 2003; 15(20): 1751–1753.

30.

Hoffman

Babay

Benita

. The design of controlled release indomethacin microspheres for oral use. Proc Int Symp Control Rel Bioact Matter 1987; 14: 115–116.

31.

Yu Y, Addai-Mensah J and Losic D. Development of nano-colloidal diatomaceous earth particles into advanced material for water treatment applications. Chemeca 2009 Proceedings, Engineers Australia, 2009. ISBN: 978-0858259225.

32.

Vrancken

Possemiers

Van Der Voort

. Surface modification of silica gels with aminoorganosilanes. Colloids Surf A 1995; 98(3): 235–241.

33.

Jani

Anglin

McInnes

. Fabrication of nanoporous anodic alumina membranes with layered surface chemistry. Chem Commun 2009; 21: 3062–3064.

34.

Addai-Mensah

Losic

. Synthesis of self-supporting gold microstructures with three-dimensional morphologies by direct replication of diatom templates. Langmuir 2010; 26(17): 14068–14072.

35.

Zhang

Sautter

Larsen

. Chemical vapor deposition of three aminosilanes on silicon dioxide: surface characterization, stability, effects of silane concentration, and cyanine dye adsorption. Langmuir 2010; 26(18): 14648–14654.

36.

Hooshmand

Keshvad

van Noort

. XPS analysis of silane films on the surface of a dental ceramic. J Adhes Sci Technol 2009; 23: 1085–1095.

37.

Sorarù

D’Andrea

Glisenti

. XPS characterization of gel-derived silicon oxycarbide glasses. Mater Lett 1996; 27(1–2): 1–5.

38.

Tanii

Hosaka

Miyake

. Preferential immobilization of biomolecules on silicon microstructure array by means of electron beam lithography on organosilane self-assembled monolayer resist. Appl Surf Sci 2004; 234(1–4): 102–106.

39.

Vrancken

Possemiers

Van Der Voort

. Surface modification of silica gels with aminoorganosilanes. Colloids Surf A 1995; 98(3): 235–241.

40.

Losic

Shapter

Gooding

. Concentration dependence in microcontact printing of self-assembled monolayers (SAMs) of alkanethiols. Electrochem Commun 2001; 3: 722–726.

41.

Watanabe

Hasegawa

Wakiyama

. Comparison between polyvinylpyrrolidone and silica nanoparticles as carriers for indomethacin in a solid state dispersion. Int J Pharm 2003; 250(1): 283–286.

42.

Watanabe

Ono

Wakiyama

. Controlled dissolution properties of indomethacin by compounding with silica. STP Pharm Sci 2002; 12: 363–367.

43.

Bonhomme

Monredon

Ribot

. Covalent grafting of organoalkoxysilanes on silica surfaces in water-rich medium as evidenced by ²⁹Si NMR. Mater Res Soc Symp Proc 2007; 1007: S09–S04.

44.

Azais

Aiello

Testa

. Preparation and solid state NMR characterization of phosphonates encapsulated in raw and organically modified SBA-15. Mater Res Soc Symp Proc 2009; 1227: JJ04–JJ06.