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Amount of hydrocortisone (HC) (A) and hydroxytyrosol (HT) (B) accumulated in the epidermis (dark bars) and dermis (lighter bars) after 24 h of Franz diffusion experiment using full-thickness of dermatomed NC/Nga mice skin. Results are presented as the amount of drug per g of skin tissue for all formulations. Data are presented as mean ± S.D, n = 3; significance (*** p < 0.001) of HC–HT-nanoparticles (NPs) against positive control (POS-C) and HC/HT co-solution groups (HC–HT-SOL).
Source publication
In this study, hydroxytyrosol (HT; a potent antioxidant) was co-administered with hydrocortisone (HC) to mitigate the systemic adverse effects of the latter and to provide additional anti-inflammatory and antioxidant benefits in the treatment of atopic dermatitis (AD). The co-loaded nanoparticles (NPs) prepared had shown different particle sizes, z...
Contexts in source publication
Context 1
... HT retained in various skin layers was approximated by using RP-HPLC and expressed as g of HC or HT retained/g of skin tissue. The total amount of HC retained in the epi- dermis (dark bars) was 1560 g/g of skin for HC-HT-NPs, which was significantly higher (p < 0.001) than that for POS-C and HC-HT-SOL, 690 and 590 g/g of skin tissue, respectively (Fig. 6(A)). In addi- tion, the data showed that the total amount of HC retained into the dermis (light bars) for HC-HT-NPs was ∼1.8 and ∼2.0 times greater than that for POS-C and HC-HT-SOL formulations as indi- cated in Fig. 6(A). Moreover, the NPs-based system (HC-HT-NPs) also showed a higher tendency toward accessibility for HT in both skin ...
Context 2
... which was significantly higher (p < 0.001) than that for POS-C and HC-HT-SOL, 690 and 590 g/g of skin tissue, respectively (Fig. 6(A)). In addi- tion, the data showed that the total amount of HC retained into the dermis (light bars) for HC-HT-NPs was ∼1.8 and ∼2.0 times greater than that for POS-C and HC-HT-SOL formulations as indi- cated in Fig. 6(A). Moreover, the NPs-based system (HC-HT-NPs) also showed a higher tendency toward accessibility for HT in both skin layers as illustrated in Fig. 6(B). Compared to HC-HT-SOL, the HC-HT-NPs showed 3.6 and 3.0 times higher total amounts of HT retained in the epidermis and dermis, respectively, which is con- sistent with findings reported ...
Context 3
... tion, the data showed that the total amount of HC retained into the dermis (light bars) for HC-HT-NPs was ∼1.8 and ∼2.0 times greater than that for POS-C and HC-HT-SOL formulations as indi- cated in Fig. 6(A). Moreover, the NPs-based system (HC-HT-NPs) also showed a higher tendency toward accessibility for HT in both skin layers as illustrated in Fig. 6(B). Compared to HC-HT-SOL, the HC-HT-NPs showed 3.6 and 3.0 times higher total amounts of HT retained in the epidermis and dermis, respectively, which is con- sistent with findings reported in previous studies (S ¸ enyi˘ git et al., ...
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Citations
... Chitosan-based NPs were prepared by Hussain et al. [141] for the topical simultaneous administration of hydrocortisone (HC) and hydroxytyrosol (HT). These NPs can be delivered topically, show increased HC and HT accumulation in the skin, and lower the risk posed by corticosteroids. ...
... Hydrocortisone/Hydroxytyrosol NPs Ionic cross-linking method There was an increase in skin retention and a decrease in flux, TEWL, intensity of erythema, skin thickness, and dermatitis index. [141] Methotrexate NPs Ultrasonication method Results show great permeation of the drug into the skin. [142] ER143 Nanocapsules Emulsion solvent evaporation method There was an increase in erythema inhibition compared to conventional treatment, an ↑ in skin retention, and skin permeation. ...
Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% of children are affected by this serious skin condition, which is painful for the sufferers. Recent research has connected the environment, genetics, the skin barrier, drugs, psychological factors, and the immune system to the onset and severity of AD. The causes and consequences of AD and its cellular and molecular origins are reviewed in this paper. The exploration of interleukins and their influence on the immunological pathway in AD has been facilitated by using relevant biomarkers in clinical trials. This approach enables the identification of novel therapeutic modalities, fostering the potential for targeted translational research within the realm of personalized medicine. This review focuses on AD’s pathophysiology and the ever-changing therapeutic landscape. Beyond the plethora of biologic medications in various stages of approval or development, a range of non-biologic targeted therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, and Abrocitinib, thus expanding the spectrum of therapeutic options. This review also addresses the latest clinical efficacy data and elucidates the scientific rationale behind each targeted treatment for atopic dermatitis.
... We discarded those samples that presented aggregates and high PDI values because it indicated a lack of stability to form the colloidal system with the NPs. Previous research has already reported an increase in particle size as a function of increasing pH [16,26,[40][41][42][43], which is attributed to particle aggregation resulting from a reduced repulsive potential on the surface of suspended CS-TPP NPs due to increasing pH in solution. This behavior could also explain the results obtained during our experimentation since Table 2 indicates a reduction in zeta potential when pH increases, probably due to the decrease of NH 3 + groups [39]. ...
Background
Polymeric nanoparticles can be used for wound closure and therapeutic compound delivery, among other biomedical applications. Although there are several nanoparticle obtention methods, it is crucial to know the adequate parameters to achieve better results. Therefore, the objective of this study was to optimize the parameters for the synthesis, purification, and freeze-drying of chitosan nanoparticles. We evaluated the conditions of agitation speed, anion addition time, solution pH, and chitosan and sodium tripolyphosphate concentration.
Results
Chitosan nanoparticles presented an average particle size of 172.8 ± 3.937 nm, PDI of 0.166 ± 0.008, and zeta potential of 25.00 ± 0.79 mV, at the concentration of 0.1% sodium tripolyphosphate and chitosan (pH 5.5), with a dripping time of 2 min at 500 rpm. The most representative factor during nanoparticle fabrication was the pH of the chitosan solution, generating significant changes in particle size and polydispersity index. The observed behavior is attributed to the possible excess of sodium tripolyphosphate during synthesis. We added the surfactants poloxamer 188 and polysorbate 80 to evaluate the stability improvement during purification (centrifugation or dialysis). These surfactants decreased coalescence between nanoparticles, especially during purification. The centrifugation increased the zeta potential to 40.8–56.2 mV values, while the dialyzed samples led to smaller particle sizes (152–184 nm). Finally, freeze-drying of the chitosan nanoparticles proceeded using two cryoprotectants, trehalose and sucrose. Both adequately protected the system during the process, and the sugar concentration depended on the purification process.
Conclusions
In Conclusion, we must consider each surfactant's benefits in formulations for selecting the most suitable. Also, it is necessary to do more studies with the molecule to load. At the same time, the use of sucrose and trehalose generates adequate protection against the freeze-drying process, even at a 5% w/v concentration. However, adjusting the percentage concentration by weight must be made to work with the CS-TPP NPs purified by dialysis.
... Hussain et al. investigated the pharmacological effects of chitosan nanoparticles loaded with hydrocortisone (HC-CNPs) in a murine model of AD induced by 2,4-dinitrofluorobenzene (DNFB) [71][72][73]. In both serum and skin High-pressure homogenization [124,125] samples, the formulation effectively inhibited inflammatory processes, reducing the release of IgE, IL-4, IL-5, IL-6, IL-13, IL-12p70, IFN-γ, TNF-α, histamine production, prostaglandin-E2 expression, and vascular endothelial growth factor (VEGF). ...
Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by a burning sensation and eczematous lesions in diverse portions of the body. The treatment of AD is exclusively focused to limit the itching, reduce inflammation, and repair the breached barrier of the skin. Several therapeutic agents for the treatment and management of AD have been reported and are in use in clinics. However, the topical treatment of AD has been an unswerving challenge for the medical fraternity owing to the impaired skin barrier function in this chronic skin condition. To surmount the problems of conventional drug delivery systems, numerous nanotechnology-based formulations are emerging as alternative new modalities for AD. Latter enhances the bioavailability and delivery to the target disease site, improves drug permeation and therapeutic efficacy with reduced systemic and off-target side effects, and thus improves patient health and promotes compliance. This review aims to describe the various pathophysiological events involved in the occurrence of AD, current challenges in treatment, evidence of molecular markers of AD and its management, combinatorial treatment options, and the intervention of nanotechnology-based formulations for AD therapeutics.
Graphical abstract
... On the other hand, at higher pH values (~7.0), most of the amino groups in Chit were in an NH 2 form and did not donate to the nanoparticles' surface charge. This increase in the particle size of nanoparticles might be because of particle agglomeration [44]. At basic pH, the amine groups become deprotonated, which leads to an increase in the turbidity of solutions with decreasing solubility. ...
... The spectrum of Gel-Alg/SeTal/HC exhibited a small band at 1742 cm − 1 and a shoulder-type band at ~ 1625 cm − 1 assigned to the C--O and C--C stretching vibrations of HC (Fig. S2). The more intense bands in the 1500-1200 cm − 1 range are also attributed to HC, confirming the presence of this compound in the film (Hussain et al., 2013). Finally, the spectrum of the film containing VitC exhibited the characteristic bands of Gel-Alg/SeTal with the additional bands observed at 3528, 1741, and 863 cm − 1 assigned to the O-H, C--O, and C-C ring stretching vibrations of VitC (Fig. S2). ...
New compounds and pharmacological strategies offer alternatives for treating chronic skin diseases, such as atopic dermatitis (AD). Here, we investigated the incorporation of 1,4-anhydro-4-seleno-d-talitol (SeTal), a bioactive seleno-organic compound, in gelatin and alginate (Gel-Alg) polymeric films as a strategy for improving the treatment and attenuation of AD-like symptoms in a mice model. Hydrocortisone (HC) or vitamin C (VitC) were incorporated with SeTal in the Gel-Alg films, and their synergy was investigated. All the prepared film samples were able to retain and release SeTal in a controlled manner. In addition, appreciable film handling facilitates SeTal administration. A series of in-vivo/ex-vivo experiments were performed using mice sensitized with dinitrochlorobenzene (DNCB), which induces AD-like symptoms. Long-term topical application of the loaded Gel-Alg films attenuated disease symptoms and pruritus, with suppression of the levels of inflammatory markers, oxidative damage, and the skin lesions associated with AD. Moreover, the loaded films showed superior efficiency in attenuating the analyzed symptoms when compared to hydrocortisone (HC) cream, a traditional AD-treatment, and decreased the inherent drawbacks of this compound. In short, incorporating SeTal (by itself or with HC or VitC) in biopolymeric films provides a promising alternative for the long-term treatment of AD-type skin diseases.
... Polymeric NPs are among the most extensively studied nanodelivery systems due to their intrinsic features including the particle size, morphology, entrapment efficiency, biodegradability, biocompatibility, colloidal stability, and good flexibility of functionalization [104][105][106][107][108][109][110]. Depending upon their architecture, polymeric NPs can be classified into (a) nanosphere and (b) nanocapsules [111]. ...
Owing to its diverse heterogeneity, aggressive nature, enormous metastatic potential, and high remission rate, the breast cancer (BC) is among the most prevalent types of cancer associated with high mortality. Curcumin (Cur) is a potent phytoconstituent that has gained remarkable recognition due to exceptional biomedical viability against a wide range of ailments including the BC. Despite exhibiting a strong anticancer potential, the clinical translation of Cur is restricted due to intrinsic physicochemical properties such as low aqueous solubility, chemical instability, low bioavailability, and short plasma half-life. To overcome these shortcomings, nanotechnology-aided developments have been extensively deployed. The implication of nanotechnology has pointedly improved the physicochemical properties, pharmacokinetic profile, cell internalization, and anticancer efficacy of Cur; however, majority of Cur-nanomedicines are still facing grandeur challenges. The advent of various functionalization strategies such as PEGylation, surface decoration with different moieties, stimuli-responsiveness (i.e., pH, light, temperature, heat, etc.), tethering of specific targeting ligand(s) based on the biochemical targets (e.g., folic acid receptors, transferrin receptors, CD44, etc.), and multifunctionalization (multiple functionalities) has revolutionized the fate of Cur-nanomedicines. This study ponders the biomedical significance of various Cur-nanomedicines and adaptable functionalizations for amplifying the physicochemical properties, cytotoxicity via induction of apoptosis, cell internalization, bioavailability, passive and active targeting to the tumor microenvironment (TME), and anticancer efficacy of the Cur while reversing the multidrug resistance (MDR) and reoccurrence in BC. Nevertheless, the therapeutic outcomes of Cur-nanomedicines against the BC have been remarkably improved after adaptation of various functionalizations; however, this evolving strategy still demands extensive research for scalable clinical translation.
Graphical Abstract
... Chitosan Ionic crosslinking Hydroxytyrosol and hydrocortisone Atopic dermatitis [41] PLGA Emulsion solvent evaporation Griffithsin and dapivirine HIV [42] Chitosan and PLGA Emulsion solvent evaporation Spantide II and ketoprofen Inflammatory [40] PCL, sorbitan monostearate, grape seed oil, polysorbate 80 ...
... Co-loaded nanoparticles of hydroxytyrosol and hydrocortisone were prepared to minimize the adverse effects of hydrocortisone and provide additional anti-inflammatory and antioxidant benefits to atopic dermatitis treatment [41]. The authors studied the effects of varying the pH of chitosan solution between 3 and 7, and reported an influence in nanoparticles' size, zeta potential, and encapsulation efficiency. ...
... Compared to the control group, co-delivery NP formulation significantly decreased transdermal water loss, erythema intensity, and dermatitis index. Consequently, the formulation demonstrated potential in the management of atopic dermatitis [41]. ...
Achieving the best possible outcome for the therapy is the main goal of a medicine. Therefore, nanocarriers and co-delivery strategies were invented to meet this need, as they can benefit many diseases. This approach was applied specifically for cancer treatment, with some success. However, these strategies may benefit many other clinical issues. Skin is the largest and most exposed organ of the human body, with physiological and psychological properties. Due to its exposition and importance, it is not difficult to understand how many skin diseases may impact on patients' lives, representing an important burden for society. Thus, this review aims to summarize the state of the art in research concerning nanocarriers and co-delivery strategies for topical agents' applications targeting skin diseases. The challenge for the medicine of the future is to deliver the drug with spatial and temporal control. Therefore, the co-encapsulation of drugs and the appropriate form of administration for them are so important and remain as unmet needs.
... In another study, CSNPs co-loaded with HC and HT (a potent antioxidant) was developed in the quest to alleviate systemic adverse effects of the HC and to provide additional anti-inflammatory and antioxidant benefits through HT for AD [105]. The co-loaded CSNPs were prepared using ionic gelation method through cross-linking between chitosan and sodium tripolyphosphate [65]. ...
... The CSNPs were reported to have different particle sizes, zeta potential (measurement of electrical charge as an indication of particle stability), loading efficiency, and morphology, when chitosan solutions of pH 3.0-7.0 were used [105]. The formulated HC-HT CSNPs significantly reduced the corresponding flux (17.04 μg/ cm 2 /h) and permeation coefficient (3.4 × 10 − 3 cm/h) of HC across full-thickness NC/Nga mouse skin using Franz diffusion cells [105]. ...
... were used [105]. The formulated HC-HT CSNPs significantly reduced the corresponding flux (17.04 μg/ cm 2 /h) and permeation coefficient (3.4 × 10 − 3 cm/h) of HC across full-thickness NC/Nga mouse skin using Franz diffusion cells [105]. Delivery of HC in the co-loaded CSNPs also showed higher epidermal (1560 ± 31 μg/g of skin) and dermal (880 ± 28 μg/g of skin) accumulation of HC compared to commercial HC formulation [105]. ...
Atopic dermatitis (AD) is a complex, relapsing inflammatory skin disease with a considerable social and economic burden globally. AD is primarily characterized by its chronic pattern and it can have important modifications in the quality of life of the patients and caretakers. One of the fastest-growing topics in translational medicine today is the exploration of new or repurposed functional biomaterials into drug delivery therapeutic applications. This area has gained a considerable amount of research which produced many innovative drug delivery systems for inflammatory skin diseases like AD. Chitosan, a polysaccharide, has attracted attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine, and has been considered a promising candidate for AD treatment due to its antimicrobial, antioxidative, and inflammatory response modulation properties. The current pharmacological treatment for AD involves prescribing topical corticosteroid and calcineurin inhibitors. However, the adverse reactions associated with the long-term usage of these drugs such as itching, burning, or stinging sensation are also well documented. Innovative formulation strategies, including the use of micro- and nanoparticulate systems, biopolymer hydrogel composites, nanofibers, and textile fabrication are being extensively researched with an aim to produce a safe and effective delivery system for AD treatment with minimal side effects. This review outlines the recent development of various chitosan-based drug delivery systems for the treatment of AD published in the past 10 years (2012–2022). These chitosan-based delivery systems include hydrogels, films, micro-, and nanoparticulate systems as well as chitosan textile. The global patent trends on chitosan-based formulations for the AD are also discussed.
... Increasing the formulation ratio between β-arbutin and CS leads to an improvement in entrapment efficiency due to the formation of larger particles with reduced surface area, resulting in a reduced diffusion of the drug out of the system [38][39][40][41]. Increasing CS concentration reduces the encapsulation efficiency of β-arbutin [42,43] and increasing CS concentration to 4 mg/mL hinders encapsulation [44,45] due to the higher solution viscosities resulting from higher CS concentrations. ...
Background: There has been an increase in demand for cosmetic skin-whitening products with efficacy toward lightening skin tone. β-arbutin is an inhibitor of tyrosinase enzyme activity within the skin’s melanocytes, and so has shown considerable promise as a skin-lightening agent. It is, however, both hydrophilic and hygroscopic, which hinders its penetration of the skin to reach these melanocytes. Chitosan (CS) possesses considerable penetration-enhancing properties when utilized in topical delivery formulations. The strong affinity of positively charged chitosan nanoparticles toward negatively charged biological membranes can be exploited to achieve site-specific targeting. Objective: To investigate the use of chitosan nanoparticles (CSNPs) as carrier units to enhance the topical delivery of β-arbutin. Method: CSNPs containing β-arbutin were prepared using an ionic cross-linking method, and entrapment efficiency and loading capacity were evaluated at numerous β-arbutin concentrations. Further characterization involved using FTIR, XRD, TEM, and TGA, and in vitro permeation studies were conducted using in vitro Franz diffusion cells. Results: β-arbutin chitosan nanoparticles were successfully formulated with a size range of 211–289 d.nm, a polydispersity index between 0.2–0.3, and zeta potential in the range 46.9–64.0 mV. The optimum encapsulation efficiency (EE) and loading capacity (LC) of β-arbutin were 68% and 73%, respectively. TEM revealed the nanoparticles to be spherical in shape. FTIR spectra revealed characteristic chitosan-related peaks appearing at 3438.3 cm−1 (-OH stretching) and 3320 cm−1 (-CH stretching), together with 1598.01 cm−1 (-NH2) specific to β-arbutin nanoparticles. XRD analysis revealed an increase in crystallinity and TGA analyses identified increasing thermal stability with increasing β-arbutin concentration. In vitro studies indicated higher permeation and improved penetration of β-arbutin loaded in CSNPs compared to its free form. Conclusion: CSNPs present considerable promise as effective carriers for improved topical delivery of β-arbutin.
... In line with these findings, previous studies reported the promising anti-inflammatory effect of hydrogels containing nanoencapsulated SB in a model of contact dermatitis induced by croton oil [7] or DNCB [8]. In addition, specifically for AD, the better performance of polymeric nanoparticles in attenuating the inflammatory and immunological effects of the disease is well documented in the literature when compared to non-nanoencapsulated substances [56,72]. Recently our research group demonstrated that pullulan films incorporated with pomegranate seed oil NC presented better biological effects than this free vegetable oil or associated into nanoemulsions against the same mice model of AD used here, highlighting the superiority of NC formulations [18]. ...
In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules was developed for topical treatment of atopic dermatitis (AD). The bilayer films were produced by applying a pullulan layer on a gellan gum layer incorporated with silibinin nanocapsules by two-step solvent casting method. The bilayer formation was confirmed by microscopic analysis. In vitro studies showed that pullulan imparts bioadhesitvity for the films and the presence of nanocapsules increased their occlusion factor almost 2-fold. Besides, the nano-based film presented a slow silibinin release and high affinity for cutaneous tissue. Moreover, this film presented high scavenger capacity and non-hemolytic property. In the in vivo study, interestingly, the treatments with vehicle film attenuated the scratching behavior and the ear edema in mice induced by 2,4-dinitrochlorobenzene (DNCB). However, the nano-based film containing silibinin modulated the inflammatory and oxidative parameters in a similar or more pronounced way than silibinin solution and vehicle film, as well as than hydrocortisone, a classical treatment of AD. In conclusion, these data suggest that itself gellan gum/pullulan bilayer film might attenuate the effects induced by DNCB, acting together with silibinin-loaded nanocapsules, which protected the skin from oxidative damage, improving the therapeutic effect in this AD-model.
