Mycobacterium tuberculosis has colonized humans since the beginning of their history. It causes the tuberculosis (TB) that, even today, is hard to treat although effective antibiotics are available. The difficulties on the treatment arise from drug resistance phenomena and from a natural protection of mycobacteria against external substances. It has been calculated that in 2012 TB caused 1.3 million of deaths worldwide. 1 One of the main cause for the incurrence of drug resistance is a low adherence of the patient to the treatment that should be carried on for approximately nine months. It has been reported that: “The repeated use of the same drugs, together with prolonged regimens that often lead to poor patient compliance, has resulted in the emergence of strains that are increasingly resistant to the available drugs.”. 2 Among the drugs used for TB therapy, rifampicin is probably the most effective but, as mentioned before, its administration, together with other drugs, take months. By a formulative point of view, rifampicin shows a solubility in water of 0.14 % w/v which could be so considered as insoluble. Thus, its formulation could present different issues for the pharmaceutical technologist, in particular, for intravenous administration. Since 2014, we have developed a drug delivery platform based on an amphiphilic derivative of inulin (INU) bioconjugated with vitamin E (VITE), called INVITE. This derivative shown its great potential in loading and releasing highly hydrophobic drugs such as curcumin or celecoxib. 3,4 This derivative showed also long-circulating features after intravenous administration. 4,5 Based on these studies we thought to load rifampicin into the INVITE nanomicelles and test these drug delivery systems for their activity against Mycobacterium smegmatis which could be considered a good model, less hazardous on manipulation with respect to Mycobacterium tuberculosis, to assess the antibacterial activity of our systems. As previously mentioned, INU was chemically derivatized with VITE and the obtained INVITE bioconjugate was allowed to form the nanomicelles and load the selected drug by the dialysis method. The drug loaded micelles were lyophilized and the gained powder was easily redispersed allowing to obtain a homogeneous dispersion in water or phosphate buffer of the insoluble drug. The calculated drug loading was 6 % w/w. The antimicrobial activity of the rifampicin loaded micelles was determined with the macrodilution broth method, according to Clinical and Laboratory Standards Institute. The results returned an effective antibacterial activity comparable to that of free rifampicin. It indicates that the drug does not show any loss in activity when included in INVITE nanomicelles so addressing the developed drug delivery system as an important tool in a perspective use of it in the therapy of TB.

Solid Lipid Nanoparticles Made of Self-Emulsifying Lipids for Efficient Encapsulation of Hydrophilic Substances

Trapani A.;Mandracchia D.;Castellani S.;Cioffi N.;Ditaranto N.;
2019

Abstract

Mycobacterium tuberculosis has colonized humans since the beginning of their history. It causes the tuberculosis (TB) that, even today, is hard to treat although effective antibiotics are available. The difficulties on the treatment arise from drug resistance phenomena and from a natural protection of mycobacteria against external substances. It has been calculated that in 2012 TB caused 1.3 million of deaths worldwide. 1 One of the main cause for the incurrence of drug resistance is a low adherence of the patient to the treatment that should be carried on for approximately nine months. It has been reported that: “The repeated use of the same drugs, together with prolonged regimens that often lead to poor patient compliance, has resulted in the emergence of strains that are increasingly resistant to the available drugs.”. 2 Among the drugs used for TB therapy, rifampicin is probably the most effective but, as mentioned before, its administration, together with other drugs, take months. By a formulative point of view, rifampicin shows a solubility in water of 0.14 % w/v which could be so considered as insoluble. Thus, its formulation could present different issues for the pharmaceutical technologist, in particular, for intravenous administration. Since 2014, we have developed a drug delivery platform based on an amphiphilic derivative of inulin (INU) bioconjugated with vitamin E (VITE), called INVITE. This derivative shown its great potential in loading and releasing highly hydrophobic drugs such as curcumin or celecoxib. 3,4 This derivative showed also long-circulating features after intravenous administration. 4,5 Based on these studies we thought to load rifampicin into the INVITE nanomicelles and test these drug delivery systems for their activity against Mycobacterium smegmatis which could be considered a good model, less hazardous on manipulation with respect to Mycobacterium tuberculosis, to assess the antibacterial activity of our systems. As previously mentioned, INU was chemically derivatized with VITE and the obtained INVITE bioconjugate was allowed to form the nanomicelles and load the selected drug by the dialysis method. The drug loaded micelles were lyophilized and the gained powder was easily redispersed allowing to obtain a homogeneous dispersion in water or phosphate buffer of the insoluble drug. The calculated drug loading was 6 % w/w. The antimicrobial activity of the rifampicin loaded micelles was determined with the macrodilution broth method, according to Clinical and Laboratory Standards Institute. The results returned an effective antibacterial activity comparable to that of free rifampicin. It indicates that the drug does not show any loss in activity when included in INVITE nanomicelles so addressing the developed drug delivery system as an important tool in a perspective use of it in the therapy of TB.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/241733
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