Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes

https://doi.org/10.1016/j.ijpharm.2019.118580Get rights and content

Highlights

  • Surfactant type/composition affect the size, stability and encapsulation efficiency of niosome.

  • Developed niosomes are highly biocompatible.

  • Developed niosomes are stable for long-term storage.

  • Controlled release of cephalexin was observed.

  • MIC value decreased for the niosomal formulation.

Abstract

In this study, optimized cephalexin-loaded niosomal formulations based on span 60 and tween 60 were prepared as a promising drug carrier system. The niosomal formulations were characterized using a series of techniques such as scanning electron microscopy, Fourier transformed infrared spectroscopy, dynamic light scattering, and zeta potential measurement. The size and drug encapsulation efficiency are determined by the type and composition of surfactant. The developed niosomal formulations showed great storage stability up to 30 days with low change in size and drug entrapment during the storage, making them potential candidates for real applications. Moreover, the prepared niosomes showed negligible cytotoxicity for HepG2 cells, measured by MTT assay. The antibacterial properties of cephalexin-loaded niosome were investigated using S. aureus and E. coli as gram-positive and gram-negative bacteria, respectively. The results showed that the encapsulation of antibiotic drug in niosomal formulation could enhance the antibacterial efficiency of the drug, where the minimum inhibitory concentration was droped from 8 µg/mL (cephalexin) to 4 µg/mL (cephalexin-loaded niosome) and from 4 µg/mL (cephalexin) to 1 µg/mL (cephalexin-loaded niosome) against E. coli and S. aureus, respectively. The findings of our study show that the improvement of cephalexin bioavailability and prolonged drug release profile could be obtained by niosomal formulation as a favorable antibiotic drug delivery system.

Introduction

In recent years, nanomaterials have received tremendous attention for diagnosis and therapy purposes (Boateng et al., 2008, Tayebi et al., 2019, Tayebi et al., 2016). Among various nanomaterials, developing drug nanocarriers have been received tremendous interest due to their enhancement in controlled, targeted drug delivery. The ideal drug delivery system (DDS) should be biocompatible, inert, mechanically stable, and have drug loading (Samad et al., 2007). Among these characteristics, most of the developed colloidal drug delivery systems suffer from toxicity at high concentrations, where does not allow to deliver the high dosage of the drug at once shot administration (Mészáros et al., 2018, Tiwari et al., 2012, Yang et al., 2008). Hence, developing nanocarriers with high biocompatibility even at their high concentrations with high drug loading capability is of importance for some medications, where high dosage of the drug is required for successful treatment (Chaikul et al., 2019, Ghosh et al., 2019, Lajevardi et al., 2018).

Infection is one of the most important examples of such a condition, where high dosage of antibiotics must be taken two-three times a day (O'Dell, 1998). The most of infections including wound infection, regional infection, expanding infection, systemic infection, mainly caused by gram-positive and gram-negative bacteria could be treated by taking cephalosporins, a sub-category of lactam antibiotics (Manosroi et al., 2013, Weinstein and Kaplan, 1970). Among them, physicians for the treatment of infectious diseases and bacterial infections are prescribing cephalexin, which is the first generation of cephalosporins (AL-Sayyed et al., 2019, Thabit et al., 2019).

Niosomes are bilayer systems based on non-ionic surfactants and cholesterol (Khan et al., 2016, Mahale et al., 2012, Marianecci et al., 2014a, Moghassemi and Hadjizadeh, 2014). The history of these vesicles back to the cosmetic industry, due to their low irradiation power, that firstly developed by L'Oreal (Buckton, 2000). These vesicles are water-soluble and highly biocompatible due to the presence of non-ionic surfactants that make them an excellent candidate to carry a high dosage of the drug, especially antibiotics, with minimum toxicity to other tissues and organs (AlQahtani et al., 2019, Li et al., 2014). In the recent decade, we have been the witness of fast developing different stimuli-responsive niosomal drug carriers(Coviello et al., 2015), especially pH-responsive niosomes(Di Francesco et al., 2017, Marianecci et al., 2016) for various targeted drug delivery applications. Despite the development of different niosomal drug delivery systems for different pharmaceutical compounds (Bazana et al., 2019, Marianecci et al., 2014a, Marianecci et al., 2014b, Primavera et al., 2018), formulation a cephalexin-based niosomal drug carrier with efficient antibacterial properties, high biocompatibility, and long storage stability has not reported yet.

In this study, we intend to develop highly-biocompatible cephalexin-loaded niosomes based on span 60 and tween 60. The effects of surfactant type and composition on physicochemical properties as well as drug encapsulation efficiency were investigated. The results indicate that the percentage of surfactants directly affect the size as well as the drug loading capacity of the developed niosomes. The developed niosomes showed almost no toxicity against HepG2 cells, while controlled drug release, as well as high antibacterial activity, was observed. The results of this work might open a new window to develop new drug carriers for different pharmaceutics and treatment of infectious diseases.

Section snippets

Chemicals

Polyoxyethylene sorbitan monostearate (Tween 60), sorbitan monostearate (Span 60), cholesterol, chloroform, phosphate buffer solution (PBS), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, penicillin–streptomycin, and dimethyl sulfoxide were purchased from Merck, Germany. .Cefalexin (Molar mass = 347.39 g/mol) was received as a gift from Daroo-Pakhsh Co. Ltd. (Tehran, Iran). Deionized water was used as an aqueous medium. All chemicals were used without any further purification.

Physicochemical properties

The effect of surfactant type on the average size and the encapsulation efficiency of the cephalexin was firstly determined using different commercial nonionic surfactants from span family, as illustrated in Table 1. As can be seen in Fig. 1a, different niosomal formulations with similar surfactants/cholesterol molar ratio and various surfactant types were exhibited varied size and polydispersity index. Among different span surfactant, the span 80-based noisome has a smaller size. This trend

Conclusion

Lately, niosomal formulations have been investigated for drug delivery system. The advantages of nisomes were greater bio-accessibility, high penetration feature. This niosomal formulation for cephalexin tries to provide niosomal drug delivery system and assess its in vitro features. A series of niosomal formulations using span 60, tween 60 and cholesterol were prepared. It was found that the entrapment efficiency of cephalexin depends on the surfactant type while increasing in HLB of

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgment

The authors would like to acknowledge the Pasteur Institute of Iran for providing the necessary laboratory facilities for this study.

Contributions

I.A. and M.T.Y. developed the idea and designed the experiments. R.G., I.A., and M.F. conducted the experiments. M.T.Y., A.L., and L.H.S. analyzed the data. M.T.Y. led the project. M.T.Y and A.L. wrote the manuscript. All authors confirmed the final manuscript before the submission.

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