Toward a Platform for the Treatment of Burns: An Assessment of Nanoemulsions vs. Nanostructured Lipid Carriers Loaded with Curcumin.

Curcumin is a highly promising substance for treating burns, owing to its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. However, its therapeutic use is restricted due to its hydrophobic nature and low bioavailability. This study was conducted to address these limitations; it developed and tested two types of lipid nanocarriers, namely nanoemulsions (NE-CUR) and nanostructured lipid carriers (NLC-CUR) loaded with curcumin, and aimed to identify the most suitable nanocarrier for skin burn treatment. The study evaluated various parameters, including physicochemical characteristics, stability, encapsulation efficiency, release, skin permeation, retention, cell viability, and antimicrobial activity. The results showed that both nanocarriers showed adequate size (~200 nm), polydispersity index (~0.25), and zeta potential (~>-20 mV). They also showed good encapsulation efficiency (>90%) and remained stable for 120 days at different temperatures. In the release test, NE-CUR and NCL-CUR released 57.14% and 51.64% of curcumin, respectively, in 72 h. NE-CUR demonstrated better cutaneous permeation/retention in intact or scalded skin epidermis and dermis than NLC-CUR. The cell viability test showed no toxicity after treatment with NE-CUR and NLC-CUR up to 125 µg/mL. Regarding microbial activity assays, free curcumin has activity against P. aeruginosa, reducing bacterial growth by 75% in 3 h. NE-CUR inhibited bacterial growth by 65% after 24 h, and the association with gentamicin had favorable results, while NLC-CUR showed a lower inhibition. The results demonstrated that NE-CUR is probably the most promising nanocarrier for treating burns.

Effect of Hydrogel Containing Achyrocline satureioides (Asteraceae) Extract-Loaded Nanoemulsions on Wound Healing Activity.

Achyrocline satureioides (Lam.) DC extract-loaded nanoemulsions have demonstrated potential for wound healing, with promising effects on keratinocyte proliferation. We carried out the first in vivo investigation of the wound healing activity of a hydrogel containing A. satureioides extract-loaded nanoemulsions. We prepared hydrogels by adding the gelling agent (Carbopol® Ultrez) to extract-loaded nanoemulsions (~250 nm in diameter) obtained by spontaneous emulsification. The final flavonoid content in formulation was close to 1 mg/mL, as estimated by ultra-fast liquid chromatography. Permeation/retention studies using porcine ear skin showed that flavonoids reached deeper layers of pig ear skin when it was damaged (up to 3.2 µg/cm² in the dermis), but did not reach the Franz-type diffusion cell receptor fluid. For healing activity, we performed a dorsal wound model using Wistar rats, evaluating the lesion size, anti-inflammatory markers, oxidative damage, and histology. We found that extract-loaded formulations promoted wound healing by increasing angiogenesis by ~20%, reducing inflammation (tumor necrosis factor α) by ~35%, decreasing lipid damage, and improving the re-epithelialization process in lesions. In addition, there was an increase in the number of blood vessels and hair follicles for wounds treated with the formulation compared with the controls. Our findings indicate that the proposed formulation could be promising in the search for better quality healing and tissue reconstruction.

Nanoemulsion Improves the Neuroprotective Effects of Curcumin in an Experimental Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. Recent studies have shown that curcumin (CUR) has neuroprotective effects in PD experimental models. However, its efficacy is limited due to low water solubility, bioavailability, and access to the central nervous system. In this study, we compared the effects of new curcumin-loaded nanoemulsions (NC) and free CUR in an experimental model of PD. Adult Swiss mice received NC or CUR (25 and 50 mg/kg) or vehicle orally for 30 days. Starting on the eighth day, they were administered rotenone (1 mg/kg) intraperitoneally until the 30th day. At the end of the treatment, motor assessment was evaluated by open field, pole test, and beam walking tests. Oxidative stress markers and mitochondrial complex I activity were measured in the brain tissue. Both NC and CUR treatment significantly improved motor impairment, reduced lipoperoxidation, modified antioxidant defenses, and prevented inhibition of complex I. However, NC was more effective in preventing motor impairment and inhibition of complex I when compared to CUR in the free form. In conclusion, our results suggest that NC effectively enhances the neuroprotective potential of CUR and is a promising nanomedical application for PD.

In vivo toxicity evaluation of nanoemulsions for drug delivery.

Lipid nanocarriers (LNs), for example nanoemulsions (NE), are an emerging tool for drug delivery due to their ability to incorporate drugs, protect the drug from degradation, improve bioavailability, and control release. Although LNs are widely studied and applied, especially in the pharmaceutical field, knowledge about their toxicity is scarce. Moreover, the majority of studies focus on their efficiency rather than safety. Thus, the aim of this study was to evaluate the possible toxic effects of NE in vivo. Male Wistar rats (2 months old, 250 g) were treated once daily for 21 days with NE via oral or intraperitoneal delivery at 200, 400 or 800 mg lipid/kg body weight. At the end of the experiment, biochemical, hematological, oxidative stress, and genotoxicity parameters were analyzed. Our results showed that treatment with NE did not modify organ weight or biochemical parameters when compared to controls. The highest NE dose (800 mg/kg) via intraperitoneal injection caused changes in hematological parameters, namely increased plasma proteins, platelets, total leukocytes, and neutrophils, findings that suggest an inflammatory reaction. Further, the same dose evoked lipid peroxidation in the liver. Taken together, the results from this study suggest that NEs can be considered safe for oral administration, but high doses via the parenteral route can cause toxic effects. This study contributes to knowledge about NE toxicity and provides important data about their safe use in the pharmaceutical field.

Healing activity of hydrogel containing nanoemulsified ß-caryophyllene.

ß-caryophyllene is a sesquiterpene present in the oil of many plant species, such as Copaifera sp., which has been shown to possesses potent anti-inflammatory action; however, its healing activity remains under study. The objectives of the present study were to produce a nanoemulsion containing ß-caryophyllene followed by a hydrogel containing nanoemulsified ß-caryophyllene, to evaluate the permeation profile in vitro, and to assess the in vivo healing activity, which is so far unexplored in the literature for pure ß-caryophyllene and in pharmaceutical formulation. The nanoemulsion was obtained through high-pressure homogenization and the hydrogel by direct dispersion with hydroxyethylcellulose. Both formulations were characterized according to droplet size, polydispersity index, volume-weighted mean diameters, particle distribution, droplets diameters tracking, zeta potential, viscosity and bioadhesion behavior. ß-caryophyllene content was determined by gas chromatography coupled with mass spectrometry (GC/MS). Both formulations presented a nanometric droplet size, negative zeta potential, high ß-caryophyllene content, and were stable for 60 days. In agreement with the viscosity results, the hydrogel containing the ß-caryophyllene nanoemulsion showed superior bioadhesiveness than the nanoemulsion. The skin permeation study in Franz cells demonstrated that isolated ß-caryophyllene was unable to cross the stratum corneum and that its nanoemulsification promoted its permeation. On the other hand, in the simulated deeply wounded skin (dermis), no significant differences were observed between the formulations and isolated ß-caryophyllene with respect to the amount of marker retention in the dermis, suggesting saturation of this skin layer. For the study of healing activity, the dorsal wound model was performed with an evaluation of the lesion size, anti-inflammatory markers, and antioxidant activity. The initial closure of the wound was achieved sooner in the group treated with the hydrogel containing the ß-caryophyllene nanoemulsion, indicating its anti-inflammatory effect. The histological analysis indicated that on day 12 day of the lesion, the hydrogel presented similar results to those of the positive control group (Dersani® oil), proving effectiveness in cutaneous tissue repair.

Reflexões bioéticas acerca da inovação em Nanomedicamentos / Reflexiones bioéticsa acerca de la innovación en Nanomedicamentos / Bioethical Reflections on Innovation in Nanomedicines / Reflexions bioètiques sobre la innovació en nanomedicaments

A nanotecnologia vem se desenvolvendo de forma exponencial na área farmacêutica, prometendo grandes benefícios, entretanto, pode estar sujeita a riscos intrínsecos relacionados a esta ciência. Neste artigo é realizada uma reflexão acerca dos desafios enfrentados pelos órgãos regulatórios em função da ausência, ou ainda, incipiente legislação, especialmente no Brasil, visto que os documentos disponíveis em relação a regulamentação, não incluem especificações para nanomedicamentos, os quais apresentam alterações na dimensão e constituição, e consequentemente comportamento diferente de medicamentos convencionais. A contingência envolvendo o desenvolvimento de nanomedicamentos e a gestão dos riscos para a vida humana e o meio ambiente fazem com que a bioética seja invocada de forma a analisar quais os impactos decorrem deste proceso

Nanotechnology has been developing exponentially in the pharmaceutical area, promising great benefits, however, it may be subject to intrinsic risks related to this science. In this article, a reflection is made on the challenges faced by regulatory agencies due to the absence or incipient legislation, especially in Brazil, since the available documents in relation to regulation do not include specifications for nanomedicine, which present changes in the dimension and constitution, and consequently different behavior of conventional drugs. The contingency involving the development of nanomedicine and the management of the risks for human life and the environment, cause bioethics to be invoked in order to analyze the impacts of this process

La nanotecnología se está desarrollando de forma exponencial en el área farmacéutica, prometiendo grandes beneficios, sin embargo, puede estar sujeta a riesgos intrínsecos relacionados a esta ciencia. En este artículo se reflexiona sobre los desafíos enfrentados por los órganos regulatorios en función de la ausencia, o aún incipiente legislación, especialmente en Brasil, ya que los documentos disponibles en relación a la reglamentación, no incluyen especificaciones para nanomedicamentos, los cuales presentan alteraciones en la dimensión y la constitución, y consecuentemente un comportamiento diferente de los medicamentos convencionales. La contingencia que involucra el desarrollo de nanomedicamentos y la gestión de los riesgos para la vida humana y el medio ambiente hacen que la bioética sea invocada para analizar qué impactos se derivan de este proceso

La nanotecnologia s'està desenvolupant de forma exponencial en l'àrea farmacèutica, prometent grans beneficis; no obstant això, pot estar subjecta a riscos intrínsecs relacionats amb aquesta ciència. En aquest article es reflexiona sobre els desafiaments que enfronten els òrgans reguladors en funció de l'absència, o d’una legislació incipient, especialment al Brasil, ja que els documents disponibles en relació a la reglamentació no inclouen especificacions per a nanomedicaments, els quals presenten alteracions en la seva dimensió i constitució, i conseqüentment presenten un comportament diferent al dels medicaments convencionals. La contingència que involucra el desenvolupament de nanomedicaments i la gestió dels riscos per a la vida humana i el medi ambient fan que la bioètica hagi de jugar un paper a fi d’analitzar quins impactes es deriven d'aquest procés