- Research article
- Open Access
Synthesis and study the controlled release of etronidazole from the new PEG/NaY and PEG/MCM-41 nanocomposites
© Zendehdel et al.; licensee BioMed Central Ltd. 2014
- Received: 19 July 2012
- Accepted: 6 January 2014
- Published: 15 January 2014
Recently, hybrid materials using poly ethylene glycol and porous nanocrystals have been developed for drug release. In this study, a series of poly ethylene glycol (PEG)/NaY zeolite and PEG/MCM-41 nanocomposites get synthesized. These materials are characterized using FT-IR spectroscopy, XRD, TGA and SEM. After loading the metronidazole onto these nanocomposites, the release of Metronidazole was studied in two kinds of release fluids simulating body fluid KH2PO4-Na2HPO4 buffer (pH = 7.4) and gastric fluid (HCl aqueous solution, pH = 1.5) while controlling the time, pH values, and temperature using UV–vis. Results showed that these nanocomposites have further release related to NaY, MCM-41 and the order of release in two pH solutions was PEG/NaY > PEG/MCM-41 > NaY > MCM-41. The behavior of drug release in these nanocomposites is probably due to hydrogen bonding interactions between drug and the hydroxyl group on the composite framework.
Controlled and sustained release of drugs is important for patients requiring medicinal treatment around the clock. Controlled release has been used extensively in food, agriculture and pharmaceutical industries to deliver active substances such as drugs, pesticides, herbicides and fertilizers . There are many groups of materials that take advantage of a controlled release system such as dendrimers , zeolites [3, 4], polymers , MCM-41 , and organic–inorganic composite materials .
Although, controlled drug delivery technologies using polymers as carriers including natural or synthetic polymers represent one of the most rapidly advancing areas of science . But, in recent years, there has been a constantly increasing interest in the application of porous silica or aluminosilcate materials as drug carriers for controlled drug release in order to meet the requirements for prolonged and better control of drug administration. Also, porous materials fulfill the requirements for homogenous distribution of drugs through the matrix in contrast to the conventionally used polymeric materials. Nano-sized particles with a well-defined morphology are receiving wide spread interest as advanced materials on the basis of a large surface area and unique physical and chemical properties which are different from bulk solids.
However inorganic materials (clay, zeolite and MCM-41) have important advantages such as high chemical and mechanical stability and low toxicity and porous structure that can be tailored to control the diffusion rate of an adsorbed or encapsulated drug; but these materials have some problems when using them in aqueous solutions and are less studied as carriers of drugs compared to organic materials such as polymers . When these materials are used in aqueous solutions in all of the applications, an accumulation of them have been observed. Under physiological conditions, porous material dispersion is unstable due to high concentrations of salt. In recent years, some polymers such as poly ethylene glycol (PEG), showed steric effects which would help to stabilize the nanoparticles preventing them from agglomeration or dispersion in solutions . PEG has been bound to silica through direct esterification of hydroxyl groups of its surface and the silica's surface silanols or through a urethane linkage in order to stabilize colloidal silica in water . In some cases, poly (ethylene glycol) attaches to the surface of the silica particles by means of hydrogen bonding; in other cases the synthesis of the silica particles takes place directly in the presence of PEG rendering ester linkages (Si-O-C) .
In this research, as a model drug, metronidazole (MTZ) was used. MTZ is a nitroimidazole derivative, particularly used in treatment of anaerobic bacteria and Protozoa infections. MTZ is the drug of choice for treatment of amoebiasis, an infection concerning the large intestine caused by Entamoeba histolytica . Metronidazole (MTZ) is frequently used in treatment of periodontal diseases since it can be used against several Gram-negative anaerobic rods, the pathogenesis of periodontitis, via inhibiting bacterial nucleic acid to synthesis .
In this contribution we tried to improve the controlled release of metronidazole. In the first section we reported the preparation and characterization of PEG/NaY zeolite and PEG/MCM-41 and at the second section we used them for releasing the metronidazole to achieve the best condition possible for drug release.
Poly (ethylene glycol) (PEG) M = 600), Cetyltrimethylammonium bromide(C19TMABr), potassium hydroxide (KOH), tetraethylorthosilicate(TEOS), N,N’ -methylen bis acrylamide (MBA), hydrogen chloride, N, N, N′, N′-tetra methyl ethylene diamine TMED), ammonium persulfate (APS), aluminum hydroxide, silica gel, sodium hydroxide, Metronidazole supplied by Merck. All of the mentioned substances were used without further purification. The Final product was characterized by X-ray Diffraction (XRD) patterns for all samples were acquired by a Bruker D8 Advance diffractometer equipped with a solid-state detector (Sol-X) set to discriminate CuKa radiation (15-130-2 h,0.02- step-scan, 10 s per step)., FT-IR (Galaxy series FT-IR 5000 spectrometer) TGA (Diamond TG/DTA Perkin Elmer). SEM (Philips, XL30).
Synthesis of NaY and MCM-41
2.1. MCM-41 was prepared in our laboratory as follow by the previously mentioned method as follows: A gel composite with molar composition: 1TEOS: 0.13 C19TMABr: 5.4 HCl: 150 H2O was prepared and stirred at room temperature for 7 days. After filtering and washing with water, the catalyst was characterized using the XRD. The NaY zeolite was prepared and activated according to the procedure described before [14, 15].
Preparation of PEG/NaY zeolite and PEG/MCM-41
The best ratio for PEG/porous material achieved through testing that which ratio has the first hour ; hence, the solution of 0.25 g PEG and 0.025 g N, N- methylene Bis acryl amide was prepared. Then, 0.35 g porous material (NaY zeolite or MCM-41) after getting dispersed by sonication was added to this solution and stirred for 30 min at room temperature. We used Ammonium per sulfate (APS) to beginnthe polymerization and N, N, N′, N′-tetra methyl ethylene diamine (TMED) as initiator was used.
Preparation 0f PEG/porous material/metronidazole
0.35 g of porous material (NaY zeolite or MCM-41) was added to a solution containing 0.30 g of metronidazole drug and acetone; then the mixture was stirred for 2 hrs and it got completely vaporized. After that, porous material/Metronidazole was added to 0.25 g PEG and 0.025 g N,N’-methylen bis acrylamide (MBA). The polymerization process carried out using ammonium persulfate (APS) as accelerator and N, N, N′, N′-tetra methyl ethylene diamine (TMED) as initiator.
Metronidazole release from PEG/porous material
PEG/porous nanocomposite were suspended in 4 ml of phosphate buffer for pH = 7.4 and pH = 1.5. we drew off the buffer solution completely at preset sampling times, and replaced it with a fresh buffer solution; Then the Metronidazole solution was filtered and testing the drug concentrations in the solution was performed by an UV–VIS spectrophotometer at (landa = 274 nm for pH = 1.5 and 317 nm for pH = 7.4).
Where k is the hydrogel swelling constant, n is the swelling ability, Mt is the amount of absorbed water at time t, and M∞ is the amount of absorbed water by the network at equilibrium time. The slope of the line obtained by plotting ln(Mt/M∞) versus ln(t) shows the values of n and k .
As it was mentioned before, the sample is synthesized by changing one monomer composition when the others are constant in each step. This changing in one monomer composition leads to developing an optimized composition of synthesized gel. Thus, optimized gel has a higher swelling rate in swelling experiments. The maximum amount of the swelling rate is 10 min for PEG/NaY and 30 min for PEG/MCM-41 (Figure 1a,b). For the higher time, the swelling rate decreases. The swelling ratio of composite with hydrogel depends on the hydrophilicity of the polymer chain, porous material and structure of hydrogel network .
Release of metronidazole from NaY zeolite, MCM-41, PEG/NaY and PEG/MCM- 41 was studied in phosphate buffer solution pH = 7.4 and artificial gastric juice pH = 1.5.
In this work poly ethylene glycol (PEG)/NaY zeolite and PEG/MCM-41 nanocomposites were synthesized and characterized using FT-IR spectroscopy, XRD, TGA and SEM that results show good interactions between PEG and porous material. In the second step metronidazole loaded onto these nanocomposites .The release of metronidazole was studied in pH = 7.4 and HCl aqueous solution and pH = 1.5 with controlled time and temperature using UV–vis. Results showed that these nanocomposites have further release related to NaY and MCM-41 and order of release in those two pH solutions were PEG/NaY > PEG/MCM-41 > NaY > MCM-41 and about 70 percent of the realease occurred in the first hours which is very suitable for the fast release of drugs in mouth and stomach. It seems like this behavior of drug release for these nanocomposites is probably due to hydrogen bonding interactions between drug and the hydroxyl group on the composite framework.
The authors wish to acknowledge Arak university for the support of this study.
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