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Development of Dipeptide N-acetyl-L-cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides.

ABSTRACT: N-acetyl-L-cysteine (NAC), a derivative of the L-cysteine amino acid, presents antioxidant and mucolytic properties of pharmaceutical interest. This work reports the preparation of organic-inorganic nanophases aiming for the development of drug delivery systems based on NAC intercalation into layered double hydroxides (LDH) of zinc-aluminum (Zn₂Al-NAC) and magnesium-aluminum (Mg₂Al-NAC) compositions. A detailed characterization of the synthesized hybrid materials was performed, including X-ray diffraction (XRD) and pair distribution function (PDF) analysis, infrared and Raman spectroscopies, solid-state ¹³carbon and ²⁷aluminum nuclear magnetic resonance (NMR), simultaneous thermogravimetric and differential scanning calorimetry coupled to mass spectrometry (TG/DSC-MS), scanning electron microscopy (SEM), and elemental chemical analysis to assess both chemical composition and structure of the samples. The experimental conditions allowed to isolate Zn₂Al-NAC nanomaterial with good crystallinity and a loading capacity of 27.3 (m/m)%. On the other hand, NAC intercalation was not successful into Mg₂Al-LDH, being oxidized instead. In vitro drug delivery kinetic studies were performed using cylindrical tablets of Zn₂Al-NAC in a simulated physiological solution (extracellular matrix) to investigate the release profile. After 96 h, the tablet was analyzed by micro-Raman spectroscopy. NAC was replaced by anions such as hydrogen phosphate by a slow diffusion-controlled ion exchange process. Zn₂Al-NAC fulfil basic requirements to be employed as a drug delivery system with a defined microscopic structure, appreciable loading capacity, and allowing a controlled release of NAC.

SUBMITTER: Eulalio D

PROVIDER: S-EPMC10054814 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Development of Dipeptide N-acetyl-L-cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides.

Eulálio Denise D Pires Figueiredo Mariana M Taviot-Gueho Christine C Leroux Fabrice F Dos Reis Serra Cristina Helena CH Faria Dalva Lúcia Araújo de DLA Constantino Vera Regina Leopoldo VRL

Pharmaceutics 20230315 3

N-acetyl-L-cysteine (NAC), a derivative of the L-cysteine amino acid, presents antioxidant and mucolytic properties of pharmaceutical interest. This work reports the preparation of organic-inorganic nanophases aiming for the development of drug delivery systems based on NAC intercalation into layered double hydroxides (LDH) of zinc-aluminum (Zn2Al-NAC) and magnesium-aluminum (Mg2Al-NAC) compositions. A detailed characterization of the synthesized hybrid materials was ...[more]

PMID: 36986816

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Project description:Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF- α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter <200 nm and highly negative zeta potential (about -30 mV). When DCs were placed in contact with NLC, imaging flow cytometry clearly showed that DCs efficiently internalized FITC-NLC, with nearly 100% of cells internalizing nanoparticles upon 1 hour of incubation. Both immature and mature DCs internalized NLC to high and comparable levels, and without cytotoxicity. Stimulating DC with TNF-α in the presence of rsv-NLC revealed that, using these nanoparticles, very small concentrations of rsv were sufficient to significantly decrease surface expression of activation marker CD83 (5 µM) and major histocompatibility complex-class II molecule human leukocyte antigen - antigen D related (10 µM), both upregulated in response to TNF-α stimulation. Rsv-NLC were compared with free rsv; at 5 µM, rsv-NLC were able to inhibit nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were needed to promote a similar effect. Taken together, the results presented show that NLC are suitable carriers of fluorescent labels or bioactive molecules for human DCs, leading to inflammation modulation.

Dataset Information

Development of Dipeptide N-acetyl-L-cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides.

Publications

Development of Dipeptide <i>N</i>-acetyl-L-cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides.

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