Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

Abstract

BackgroundTuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6–24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB.ResultAn anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner.ConclusionsSustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis.

Inorganic nanolayers: structure, preparation, and biomedical applications

“…In this method, metal oxide is dissolved in the solution of the desired anions, and the pH is raised until precipitation occurs. 37,39 The results are more fruitful if the desired anion solution is acidic in nature. 37,39 Varieties of organic and inorganic anions have been intercalated using these two methods.…”

“…37 They have also designed a similar sustainedrelease PAS ZnLH nanocomposite with higher drug loading by using zinc nitrate as a precursor. 152 Both of these nanocomposite formulations were found to be highly biocompatible with normal human lung fibroblast cells (MRC-5) and 3T3 fibroblast cells.…”

“…[37][38][39] In the first method, salt is used as the starting material, which is dissolved in aqueous solution and its pH is increased by the slow addition of basic solutions, such as sodium hydroxides, aqueous solution of ammonia, or aqueous carbonate, until precipitation occurs. 40 This method is very much similar to the coprecipitation method used in LDH preparation, where aqueous salt solutions are coprecipitated with counteranions of interest.…”

Development of a biocompatible nanodelivery system for tuberculosis drugs based on isoniazid-Mg/Al layered double hydroxide

“…[34][35][36] In brief, normal human lung fibroblast MRC-5 healthy cells and 3T3 mouse fibroblast cells were procured from ATCC. Cells were cultured in DMEM and RPMI 1,640 media containing 10% fetal bovine serum and growth medium containing 100 units/mL penicillin and 50 µg/mL streptomycin; cells were maintained at 37°C in a humidified atmosphere of 5% CO 2 .…”

Synthesis, characterization, and efficacy of antituberculosis isoniazid zinc aluminum-layered double hydroxide based nanocomposites

“…Biocompatible nanodelivery systems could enhance the therapeutic efficacy of the drug and would ultimately improve patients' compliance to the chemotherapy of TB. 14,21,22 In recent years, inorganic nanolayers, namely, layered double hydroxides (LDHs), have emerged as biocompatible drug delivery systems with excellent characteristics, such as ease of preparation, tendency of loading various pharmaceutical drugs, release of the drugs in a sustained manner, biocompatibility, and biodegradability. 15,[22][23][24] Excellent reviews have been written by Saifullah and Hussein 25 and Rives et al 26,27 describing in detail the drug delivery applications of LDHs.…”