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Development of A New Delivery System Based on Drug-Loadable Electrospun Nanofibers for Psoriasis Treatment.

ABSTRACT: Psoriasis is a chronic autoimmune systemic disease with an approximate incidence of 2% worldwide; it is commonly characterized by squamous lesions on the skin that present the typical pain, stinging, and bleeding associated with an inflammatory response. In this work, poly(methyl vinyl ether-alt-maleic ethyl monoester) (PMVEMA-ES) nanofibers have been designed as a delivery vehicle for three therapeutic agents with palliative properties for the symptoms of this disease (salicylic acid, methyl salicylate, and capsaicin). For such a task, the production of these nanofibers by means of the electrospinning technique has been optimized. Their morphology and size have been characterized by optical microscopy and scanning electron microscopy (SEM). By selecting the optimal conditions to achieve the smallest and most uniform nanofibers, approximate diameters of up to 800?900 nm were obtained. It was also determined that the therapeutic agents that were used were encapsulated with high efficiency. The analysis of their stability over time by GC-MS showed no significant losses of the encapsulated compounds 15 days after their preparation, except in the case of methyl salicylate. Likewise, it was demonstrated that the therapeutic compounds that were encapsulated conserved, and even improved, their capacity to activate the transient receptor potential cation channel 1 (TRPV1) channel, which has been associated with the formation of psoriatic lesions.

SUBMITTER: Martinez-Ortega L

PROVIDER: S-EPMC6359116 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Development of A New Delivery System Based on Drug-Loadable Electrospun Nanofibers for Psoriasis Treatment.

Martínez-Ortega Leticia L Mira Amalia A Fernandez-Carvajal Asia A Mateo C Reyes CR Mallavia Ricardo R Falco Alberto A

Pharmaceutics 20190104 1

Psoriasis is a chronic autoimmune systemic disease with an approximate incidence of 2% worldwide; it is commonly characterized by squamous lesions on the skin that present the typical pain, stinging, and bleeding associated with an inflammatory response. In this work, poly(methyl vinyl ether-<i>alt</i>-maleic ethyl monoester) (PMVEMA-ES) nanofibers have been designed as a delivery vehicle for three therapeutic agents with palliative properties for the symptoms of this disease (salicylic acid, me ...[more]

PMID: 30621136

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Project description:The electrospinning of hydrocortisone/cyclodextrin complex nanofibers was performed in order to develop a fast-dissolving oral drug delivery system. Hydrocortisone is a water-insoluble hydrophobic drug, yet, the water solubility of hydrocortisone was significantly enhanced by inclusion complexation with hydroxypropyl-beta-cyclodextrin (HP-β-CyD). In this study, hydrocortisone/HP-β-CyD complexes were prepared in aqueous solutions having molar ratios of 1/1, 1/1.5 and 1/2 (hydrocortisone/HP-β-CyD). Highly concentrated aqueous solutions of HP-β-CyD (180%, w/v) were used for hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) in order to perform electrospinning without the use of an additional polymer matrix. The turbidity of hydrocortisone/HP-β-CyD (1/1 and 1/1.5) aqueous solutions indicated the presence of some uncomplexed crystals of hydrocortisone whereas the aqueous solution of hydrocortisone/HP-β-CyD (1/2) was homogeneous indicating that hydrocortisone becomes totally water-soluble by inclusion complexation with HP-β-CyD. Nonetheless, the electrospinning of hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) successfully yielded defect-free uniform nanofibrous structures. Moreover, the electrospinning process was quite efficient that hydrocortisone was completely preserved without any loss yielding hydrocortisone/HP-β-CyD nanofibers having the initial molar ratios (1/1, 1/1.5 and 1/2). The structural and thermal characterization of the hydrocortisone/HP-β-CyD nanofibers revealed that hydrocortisone was totally inclusion complexed with HP-β-CyD and was in the amorphous state in hydrocortisone/HP-β-CyD (1/2) nanofibers whereas some uncomplexed crystalline hydrocortisone was present in hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibers. Nevertheless, hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) complex aqueous systems were electrospun in the form of nanofibrous webs having a free-standing and flexible nature. The hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibrous webs have shown fast-dissolving behavior in water or when they were in contact with artificial saliva. Yet, the hydrocortisone/HP-β-CyD (1/2) nanofibrous web dissolved more quickly than the hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibrous webs due to the full inclusion complexation and the amorphous state of hydrocortisone in this sample. In short, the results suggest that polymer-free electrospun nanofibrous webs produced from hydrocortisone/HP-β-CyD could be quite applicable for fast-dissolving oral drug delivery systems.

Project description:Piroxicam (Px) is a nonsteroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis and rheumatoid arthritis. It is administered orally; however, its poor water solubility causes low loading to the nonconventional drug delivery systems (DDSs), such as electrospun fibers. Furthermore, the rapid dissolution of DDS and fast release of the embedded drugs are crucial for oral delivery of drugs to patients who are unconscious or suffering from dysphagia. In this regard, this study reports the development of rapidly dissolving cyclodextrin (CD)-based inclusion complex (IC) nanofibers by waterborne electrospinning for fast oral delivery of Px. Scanning electron microscopy analysis revealed the formation of bead-free fibers with a mean diameter range of 170-500 nm at various concentrations of Px; increasing the Px loading decreased the fiber diameter. The formation of IC was demonstrated by X-ray diffraction (XRD) analysis by the disappearance of crystalline peaks of Px. Likewise, differential scanning calorimetry (DSC) analysis showed the disappearance of the melting peak of the embedded Px due to IC formation. Both Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) confirmed the presence of Px within the fibers. 1H NMR experiments demonstrated Px preservation in the fibers after six months. Px-loaded nanofibers were employed for sublingual drug delivery. To mimic the environment of the mouth, the nanofibers were treated with artificial saliva, which revealed the instant dissolution of the nanofibers. Furthermore, dissolution experiments were performed on the tissues wetted with artificial saliva, where the dissolution of the fibers could be extended to a few seconds, demonstrating the suitability of the materials for sublingual oral drug delivery. Overall, this paper, for the first time, reports the rapid oral delivery of Px from polymer-free CD fibers produced by waterborne electrospinning without the requirement of any carrier polymer and toxic solvent.

Dataset Information

Development of A New Delivery System Based on Drug-Loadable Electrospun Nanofibers for Psoriasis Treatment.

Publications

Development of A New Delivery System Based on Drug-Loadable Electrospun Nanofibers for Psoriasis Treatment.

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