Search

This study aimed to develop mucoadhesive chitosan-based films capable of enhancing the curcumin penetration into the oral mucosa to treat oral cancers. We developed three films containing medium molecular weight chitosan (190-310 KDa) and other excipients (polyvinyl alcohol, Poloxamer®407, and propylene glycol) that have proven to be compatible with each other and with curcumin in thermal analyses. The films were smooth, flexible, and precipitates free, with uniform weight and thickness, pH compatible with the oral mucosa, resistance to traction, and entrapped curcumin in a high proportion. They also exhibited necessary swelling and mucoadhesion for tissue adherence. Ex vivo penetration studies proved that the films significantly increased the penetration of curcumin into the oral mucosa compared to control, even when the mucosa was subjected to a condition of simulated salivation. Curcumin exhibited cytotoxic activity in vitro in the two head and neck cancer cell lines (FaDu, SCC-9) at doses close to those found in penetration studies with the films. When combined with radiotherapy, curcumin demonstrated superiority over single doses of radiotherapy at 4, 8, and 12 Gy. Therefore, the developed films may represent a promising alternative for the topical treatment of oral tumors., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Naringenin is a bioflavonoid mainly found in citrus fruits. It presents many pharmacological benefits, including a remarkable anti-inflammatory activity, but its oral bioavailability is poor. To overcome this drawback, this work proposes a transdermal administration of such bioflavonoid, considering its use in the chronic treatment of inflammatory conditions. For this, it aims to develop a chitosan-based film that guarantees a consistent transdermal delivery of the drug. First, naringenin's in vitro anti-inflammatory effect on T-cell proliferation was evaluated, followed by research on the modulation of gene expression for inflammatory factors in peripheral blood mononuclear cells. Chitosan films were then prepared and characterized. Afterward, naringenin release profile from a selected film was determined as well as the drug permeation across porcine skin provided by the film. Naringenin induced the expression of the anti-inflammatory factors IL-10 and TGF-β1 while inhibiting the expression of the pro-inflammatory cytokine IL-1β and limiting T-cell proliferation. The chitosan film was successfully developed, and the drug was progressively released to the physiological media following both first order and Korsmeyer-Peppas kinetics. When topically applied, the chitosan film guaranteed a constant and continuous diffusion of naringenin across the skin over 72 h. Indeed, the permeation flux of naringenin was 0.30 ± 0.01 µg/cm 2 /h, which means a concentration in the receptor solution 14-fold (p < 0.05) higher than that provided by the drug solution. Thus, the chitosan film represents a promising transdermal alternative for the long-term treatment of inflammatory conditions using naringenin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We developed chitosan or hyaluronic acid nanoparticles to entrap clindamycin and evaluated for the first time the impact of these two polymeric nanosystems on the targeted drug delivery to the pilosebaceous units, considering the sebaceous characteristics of skin affected by acne. Chitosan and hyaluronic acid nanoparticles respectively presented diameters of 362 ± 19 nm and 417 ± 9 nm (PDI < 0.47), entrapped 42 % and 48 % of the clindamycin content (drug loading of 8.8 % and 0.5 %) and had opposite surface charges (+27.7 ± 0.9 mV and -30.2 ± 2.7 mV). Although only the hyaluronic acid nanoparticles showed increased deposition of the drug into the pilosebaceous structures, both nanoparticles revealed enhanced targeted delivery of clindamycin to these structures as compared to commercial formulation (53 ± 20 % and 77 ± 9% of the total drug that penetrated the skin was found on the pilosebaceous units from, respectively, chitosan and hyaluronic acid nanoparticles). Remarkably, the "targeting potential" of the nanoparticles was more pronounced when the skin was pretreated to simulate a sebaceous condition. In conclusion, both polymeric nanocarriers targeted drug delivery to the pilosebaceous structures at different extensions and, in the case of oily skin conditions, such targeting was increased., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Tumors located in the oral mucosa are challenging to treat since surgery can lead to aesthetic, speech, and salivation problems, radiotherapy alone is often ineffective, and systemic chemotherapy brings meaningful side effects to the patient. Here, we proposed to develop mucoadhesive chitosan nanoparticles entrapping the chemotherapeutic oxaliplatin (OXPt) and to evaluate ex vivo its penetration in porcine mucosa under both passive and iontophoretic topical treatments. OXPt-loaded chitosan nanoparticles presented a small hydrodynamic size (188 ± 20 nm), narrow distribution (PDI of 0.28 ± 0.02) and positive zeta potential (+44.8 ± 2.8 mV). These nanoparticles provided a "burst effect" on drug release followed by a longer-term controlled release. When applied to the oral mucosa, the chitosan nanoparticles increased 3-fold drug penetration, and this rate was maintained even when the mucosa was "washed" with a buffer to mimic salivation. Iontophoresis doubled the amount of OXPt transported to the mucosa. These amounts exceeded the dose required to cause cell death of an oral tumor cell line. Besides, chitosan nanoparticles increased the rate of cells that entered into apoptosis. In summary, this study points to the feasibility of topical therapy with chitosan nanoparticles, potentialized by the application of iontophoresis, to treat oral tumors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives The aim of this study was to investigate in vitro the epidermal targeting potential of clobetasol propionate-loaded nanostructured lipid carriers ( CP- NLC) when compared to that of chitosan-coated ( CP- NLC-C). Methods CP- NLC were prepared by microemulsion method and characterized by dynamic light scattering, transmission electron microscopy, in vitro release and permeation studies. To verify epidermal targeting, permeation studies were performed in two sets of experiments. For the first set, the skin was removed from the diffusion cell and stratum corneum ( SC) was separated from the remaining skin ( RS). For the second set, the whole epidermis ( EP) was separated from the dermis ( DER). CP quantification was performed in each skin layer. Key findings A novel clobetasol propionate-loaded NLC was produced with 1/5th of the drug dose used in commercial formulations and, even so, presented greater skin permeation. Both chitosan-coated and uncoated NLC enhanced the amount of CP in the epidermis more than 80-fold when compared to the commercial formulation (20.26 ± 2.77; 17.85 ± 0.49 and 0.22 ± 0.02 μg/cm2, respectively). Differently from chitosan-coated NLC, the uncoated NLC did not show dermal retention. Conclusions NLC proved to be a system with potential for targeting drug delivery to the epidermal layer. [ABSTRACT FROM AUTHOR]

In general, nanometer-sized drug delivery systems have a natural tendency for accommodation in the follicular cavities, which makes them advantageous in the treatment of conditions affecting these structures. Still, follicular targeting enhancement can improve therapy outcomes. Here, we compare two strategies to further promote dutasteride follicular-targeted delivery: the chemical modulation of nanosystem surface properties by coating with the natural polymer chitosan, and the application of a massage. For this, poly-(ɛ-caprolactone)-lipid-core nanocapsules (NC) containing dutasteride were developed and had their permeation profile compared to chitosan-coated nanocapsules (NC-CS). Nanocapsules showed high drug encapsulation efficiency (>94%), and stability for up to 90 days of storage. As expected, chitosan coating increased the size and zeta potential, from 199.0 ± 0.5 nm (PdI of 0.12) and − 13.6 ± 0.6 mV to 224.9 ± 3.4 nm (PdI 0.23) and + 40.2 ± 0.8 mV, respectively. Both coated and non-coated nanoparticles targeted the hair follicles compared to a drug solution. Enhanced hair follicles targeting was observed after the massage procedure, with 5 and 2-fold increases relative to NC and NC-CS, respectively. In conclusion, this work demonstrates dutasteride nanocapsules can target the follicular casts, and a simple physical stimulation can enhance 5-times the drug amount accumulated. [ABSTRACT FROM AUTHOR]