Nanocapsule Suspensions Research Articles

Development of a hydrogel containing bisabolol-loaded nanocapsules for the treatment of atopic dermatitis in a Balb/c mice model

α-Bisabolol (αBIS), a plant-derived compound with anti-inflammatory properties, is potentially a therapeutic agent for Atopic dermatitis. However, its poor water solubility and photoinstability limit its topical application. Therefore, the present study, aimed to develop cationic polymeric nanocapsules of αBIS to improve its skin delivery, photostability, and therapeutic efficacy. The αBIS-loaded nanocapsules were prepared using the solvent displacement technique. A Box-Behnken (BB) design was employed to statistically optimize formulation variables and αBIS-loaded nanocapsules characterized by particle size, surface charge and encapsulation efficiency. The optimal formulation was selected, and the spherical shape of the nanocapsules was confirmed by scanning electron microscopy (SEM). Furthermore, hydrogel containing αBIS-loaded nanocapsules was prepared by thickening of nanocapsule suspension with Carbopol 934 and evaluated for rheology, in vitro drug release and skin permeation. Furthermore, a mice model of atopic dermatitis was used to evaluate the anti-inflammatory potential of the hydrogels. The optimal formulation displayed a spherical morphology under scanning electron microscopy (SEM) with an optimum particle size of 133.00 nm, polydispersity index (PDI) of 0.12, high EE% of 93 %, and improved optical stability of αBIS in the prepared nanocapsules compared to the free drug. The nano-based hydrogels demonstrated non-Newtonian pseudoplastic behavior and an increased αBIS in vitro release profile without causing skin irritation in rabbits. Drug retention within the dermis and epidermis layers significantly surpassed that of drug-free hydrogel. Moreover, in vivo histopathological studies and myeloperoxidase (MPO) enzyme activity, revealed that hydrogel containing bisabolol nanocapsules exhibited The best anti-inflammatory effect. The results showed that hydrogels containing bisabolol nanocapsules markedly alleviated dermatitis-related inflammation and reduced skin thickness in Balb/c mice. Our findings support nanocapsules as an effective drug delivery system to enhance αBIS stability, bioavailability, and therapeutic efficacy in AD treatment.

4-(Phenylselanyl)-2H-chromen-2-one-Loaded Nanocapsule Suspension-A Promising Breakthrough in Pain Management: Comprehensive Molecular Docking, Formulation Design, and Toxicological and Pharmacological Assessments in Mice.

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients' quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa β. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation.

Co-encapsulation of chloroquine plus colchicine in cationic nanocapsule suspensions: Technological development and toxicological evaluation

This study aimed to co-nanoencapsulate chloroquine (CQ) and colchicine (CC) and evaluate the toxicity of the drug combination as a potential treatment for malaria. A pre-formulation chemical compatibility study was carried out to evaluate the feasibility of co-nanoencapsulation of drugs with excipients. Nanocapsules containing CQ + CC (1 + 0.5 mg/mL, respectively) were prepared with Eudragit RS®100 and developed using the nanoprecipitation method and then characterized. The in vitro release of the drug was tested at pH 7.4 using a dialysis bag, and acute in vivo toxicity was evaluated at doses of 5 and 20 mg/kg of CQ and 2.5 and 10 mg of CC, with free solution and nanoformulation groups, in male Wistar rats. Locomotor activity, motor coordination, leukocyte count, biochemical profile, tissue oxidative stress, histopathology, and relative weight of all organs were determined. Differential scanning calorimetry and thermogravimetric analyses revealed minimal interaction between drugs and the excipients. Cationic nanocapsules presented 238 ± 6 nm, +15.8 ± 1.1 mV, and 4.6 ± 0.1 pH and drug content (%) close to theoretical values, remaining stable for 90 days. The nanoencapsulation controlled the release of both drugs, showing a biexponential kinetics. No signs of toxicity were observed in animals treated with free or nanoencapsulated drugs at both doses. Therefore, the co-nanoencapsulated CQ plus CC is a promising candidate for antimalarial testing.

Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150nm with a narrow size distribution, the zeta potential was around + 6mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

Oxybenzone-loaded Polymeric Nanocapsule Gel: Strategy to Reduce Skin Penetration and Drug-induced Irritation

Aim: This work aimed to determine whether the oxybenzone-loaded nanocapsule gel (NC gel) can reduce the degree of skin penetration and, thereby, the skin irritation caused by the drug. Background: Sunscreens must be retained on the uppermost skin surface, forming a protective film throughout the entire UV exposure period. Skin penetration and/or light-induced decomposition of sunscreens is undesirable as this would decrease the expected UV protection. The changes in colour and appearance of the sunscreen, as well as the possible increase in the phototoxicity and allergenic potential of sunscreen breakdown products, are also of concern. : Furthermore, exposure to UVB radiation leads to impairment in the stratum corneum and hence enhances the skin's penetration of sunscreen actives, leading to systemic absorption. Currently, available sunscreen agents are low-molecular-weight lipophilic molecules, which make them capable of penetrating the skin and being systemically absorbed. : Oxybenzone is an organic compound widely used in commercial sunscreen preparations. The low molecular weight and lipophilic nature of oxybenzone facilitate penetration through the stratum corneum, leading to irritation and allergic reactions. : Polymeric nanocapsules (NCs) have been developed to ensure a controlled release of pharmaceutical and cosmetic agents and/or exert a preventive effect against the harmful side effects induced by direct contact of tissues with high amounts of the drug. Hence, we hypothesised that encapsulating the oxybenzone polymeric nanocapsule system would reduce the irritation and its allergic potential upon topical application. Objective: The current study aimed to develop a polymeric nanocapsule-based gel of oxybenzone and investigate its skin deposition by ex vivo permeation studies. Methods: The polymeric nanocapsules were prepared by the solvent displacement method using a combination of Eudragit RSPO and Eudragit RLPO polymers. Further nanocapsules were incorpo-rated into the xanthan gum gel base. It was evaluated for particle size, PDI, zeta potential, drug con-tent, in vitro release, ex vivo permeation, sunscreen efficacy and skin irritation potential by the HET CAM test. Results: Particle size, PDI, zeta potential, percent encapsulation, and loading of drug-loaded nanocap-sule suspension were found to be 237.1 nm, 0.189 + 58.4 mV, 852 + 0.5%, and 19.45 + 0.94%, re-spectively. DSC results indicate the suitability of selected excipients. In vitro release studies indicated 68.99% oxybenzone release from NC suspension, while NC gel showed 58.87% at the end of 24 hrs. Ex vivo permeation results showed significantly higher drug permeation from plain oxybenzone gel than NC gel. Permeation flux and reduction ratio suggest a three-fold reduction in skin permeation by NC gel. The gel offered medium-level sun protection with an SPF value of 22.12. According to the HET CAM study, there was no evidence of skin irritation caused by NC gel. Conclusion: It is concluded that the encapsulation of oxybenzone prevents direct interaction with the skin, reducing the chances of skin irritation and penetration. Results suggest that nanocapsules in gel bases can provide a promising formula for safer topical delivery of sunscreen.

Copper-coated phase change nanocapsules with improved thermal properties synthesized by a green method

This study aims to develop an eco-friendly method for synthesizing phase change nanocapsules with improved thermal properties. It focuses on coating nanocapsules with highly thermal conductive Cu, using a non-toxic reducing agent. The morphology, microstructure, crystal structure, element compositions, and thermal stability of the Cu-coated nanocapsules were analyzed to ensure successful nanoencapsulation and coating. Melting-solidifying cycling experiments were conducted to assess the thermal reliability of the nanocapsules and the thermal conductivity of their suspensions was measured. The results indicated that the nanocapsules were continuously coated with Cu under appropriate reaction conditions. The optimal preparation conditions were determined, resulting in a phase change enthalpy of 77.42 kJ/kg. The SiO2 shell and Cu coating increased the thermal stability of the nanocapsules, with a mere 7.59 kJ/kg reduction in melting enthalpy after 250 melting-solidifying cycles. The thermal conductivity of the Cu-coated nanocapsule suspension increased by 26.67 % compared to that of the uncoated nanocapsules.

Cationic nanocapsule suspension as an alternative to the sublingual delivery of nifedipine

Nifedipine (NIFE) is a calcium channel blocker drug used to treat cardiovascular diseases, angina, and hypertension. However, NIFE is photolabile, has a short biological half-life, low aqueous solubility, and undergoes an intense first-pass effect, compromising its oral bioavailability. Thus, this study aimed to develop NIFE-loaded nanocapsules for sublingual administration. Nanocapsule suspensions of Eudragit® RS100 and medium chain triglycerides containing NIFE were prepared by the interfacial deposition of preformed polymer technique. The developed formulations showed particle size around 170 nm, polydispersity index below 0.2, positive zeta potential, and acid pH. The NIFE content was 0.98 ± 0.03 mg/mL, and the encapsulation efficiency was 99.9%. The natural light photodegradation experiment showed that the nanocapsules were able to provide NIFE photoprotection. The nanocapsules reduced the cytotoxicity of NIFE and showed no genotoxic effects in the Allium cepa model. Through the HET-CAM test, the formulations were classified as non-irritating. The developed nanocapsule suspension demonstrated a controlled release of NIFE and mucoadhesive potential. The in vitro permeation assay showed that the nanocapsules favored the NIFE permeation to the receptor compartment. In addition, the nanocapsules provided greater drug retention in the mucosa. Thus, the development of polymeric nanocapsule suspensions showed that this system could be a promising platform for NIFE sublingual administration.

Development of Guar Gum Hydrogel Containing Sesamol-Loaded Nanocapsules Designed for Irritant Contact Dermatitis Treatment Induced by Croton Oil Application.

Irritant contact dermatitis is usually treated with corticosteroids, which cause expressive adverse effects. Sesamol is a phenolic compound with anti-inflammatory and antioxidant properties. This study was designed to evaluate a hydrogel containing sesamol-loaded ethylcellulose nanocapsules for the treatment of irritant contact dermatitis. The nanocapsules presented a size in the nanometric range, a negative zeta potential, a sesamol content close to the theoretical value (1 mg/mL), and a 65% encapsulation efficiency. Nanoencapsulation protected sesamol against UVC-induced degradation and increased the scavenging activity assessed by ABTS and DPPH radicals. The hydrogels were prepared by thickening the nanocapsule suspensions with guar gum (2.5%). The hydrogels maintained the nanometric size of the nanocapsules and a sesamol content of approximately 1 mg/g. The HET-CAM assay classified the hydrogels as nonirritating. The in vitro release of the hydrogel containing sesamol in the nanoencapsulated form demonstrated an initial burst effect followed by a prolonged sesamol release and a lower skin permeation in comparison with the hydrogel containing free sesamol. In addition, it exhibited the best anti-inflammatory effect in the irritant contact dermatitis model induced by croton oil, reducing ear edema and inflammatory cells infiltration, similar to dexamethasone (positive control). Therefore, the hydrogel containing sesamol in the nanoencapsulated form seemed to have a therapeutic potential in treating irritant contact dermatitis.

Locust bean gum-based hydrogel containing nanocapsules for 3,3′-diindolylmethane delivery in skin inflammatory conditions

A hydrogel based on polymeric nanocapsules containing 3,3′-diindolmethane (DIM) was developed for the treatment of skin inflammatory disorders. Nanocapsule suspensions were prepared by interfacial deposition of preformed polymer method and thickened using locust bean gum (3%) to obtain hydrogels. The hydrogels showed satisfactory DIM content (1 mg/g), pH in the neutrality range (6.59–6.82), particle size in nanometric scale (around 140 nm) and non-Newtonian pseudoplastic behavior. In addition, nano-based formulations showed a greater amount of DIM released in vitro, and a smaller amount of active in the dermis was observed in the evaluation of skin permeation. The HET-CAM assay classified the hydrogels as non-irritating. Finally, the performance of hydrogels in two in vivo models of skin inflammation was evaluated. The evaluation of the anti-inflammatory effect in a model induced by croton oil showed that the nano-based hydrogels maintained the DIM activity, reducing ear edema and leukocyte infiltration. Regarding the UVB radiation-induced inflammation model, only nano-based hydrogels prolonged the in vivo anti-inflammatory effect of DIM up to 48 h, indicating a prolonged effect for nanocapsules. Therefore, the nano-based hydrogels demonstrate advantageous characteristics that may enhance the effects of DIM when applied to the skin, which may be of interest in the treatment of cutaneous inflammatory disorders.

Locust Bean Gum Nano-Based Hydrogel for Vaginal Delivery of Diphenyl Diselenide in the Treatment of Trichomoniasis: Formulation Characterization and In Vitro Biological Evaluation.

Trichomoniasis is the most common nonviral sexually transmitted infection in the world, but its available therapies present low efficacy and high toxicity. Diphenyl diselenide (PhSe2) is a pharmacologically active organic selenium compound; however, its clinical use is hindered by its lipophilicity and toxicity. Nanocarriers are an interesting approach to overcome the limitations associated with this compound. This study designed and evaluated a vaginal hydrogel containing PhSe2-loaded Eudragit® RS100 and coconut oil nanocapsules for the treatment of trichomoniasis. Nanocapsules presented particle sizes in the nanometric range, positive zeta potential, a compound content close to the theoretical value, and high encapsulation efficiency. The nanoencapsulation maintained the anti-Trichomonas vaginalis action of the compound while improving the scavenger action in a DPPH assay. The hydrogels were prepared by thickening nanocapsule suspensions with locust bean gum (3%). The semisolids maintained the nanometric size of the particles and the PhSe2 content at around the initial concentration (1.0 mg/g). They also displayed non-Newtonian pseudo-plastic behavior and a highly mucoadhesive property. The chorioallantoic membrane method indicated the absence of hemorrhage, coagulation, or lysis. The compound, from both non-encapsulated and nano-based hydrogel delivery systems, remained on the surface of the bovine vaginal mucosa. Therefore, the formulations displayed the intended properties and could be a promising alternative for the treatment of trichomoniasis.

One-Step Construct Responsive Lignin/Polysaccharide/Fe Nano Loading System Driven by Digestive Enzymes of Lepidopteran for Precise Delivery of Pesticides.

A strategy that relies on the differences in feeding behavior between pests and natural enemies to deliver insecticides precisely was proposed. After proving that the digestive enzymes in Lepidopteran pests can act as triggers for lignin-based controlled-release carriers, a novel multiple-enzyme-responsive lignin/polysaccharide/Fe nanocarrier was constructed by combining the electrostatic self-assembly and chelation and loaded with lambda-cyhalothrin (LC) to form a nanocapsule suspension loading system. The nanocapsules were LC@sodium lignosulfonate/chitosan/Fe (LC@SL/CS/Fe) and LC@sodium lignosulfonate/alkyl polyglycoside quaternary ammonium salt/Fe (LC@SL/APQAS/Fe). LC@SL/APQAS/Fe was more stable than LC@SL/CS/Fe because it adsorbs more Fe3+, and the half-lives of LC in LC@SL/APQAS/Fe under UV irradiation were prolonged at 4.02- and 6.03-folds than those of LC@SL/CS/Fe and LC emulsifiable concentrate (LC EC), respectively. Both LC@SL/APQAS/Fe and LC@SL/CS/Fe have responsive release functions to laccase and cellulase, and the release rate of the former was slower. The insecticidal activity of LC@SL/APQAS/Fe against Agrotis ipsilonis was similar to those of LC@SL/CS/Fe and LC EC, while the toxicity of LC@SL/APQAS/Fe to the natural enemy was 2-3 times less than those of LC@SL/CS/Fe and LC EC. Meanwhile, the organic solvent component in the nanocapsule suspension was 94% less than that in the EC preparation. Therefore, the nano loading system based on SL/APQAS/Fe is a promising nanoplatform with the advantages of high efficiency, low toxicity, and environmental friendliness.

Redispersible 3D printed nanomedicines: An original application of the semisolid extrusion technique

Semisolid extrusion is a layer-by-layer 3D printing technique that produces objects from gels or pastes. This process can be carried out at room temperature, without using a light source, and has been explored in pharmaceutics in the last few years. In this regard, our group hypothesized its suitability for the production of three-dimensional (3D) printed nanomedicines containing drug-loaded organic nanocarriers. In this study, the original application of the semisolid extrusion was evaluated to produce redispersible 3D printed oral solid forms containing drug-loaded polymeric nanocapsules. A carboxymethyl cellulose hydrogel containing resveratrol and curcumin co-encapsulated in nanocapsules was prepared, and the nanocapsules did not change its complex viscosity and yield stress. Homogeneous and yellow cylindrical-shaped solid forms were printed, with a mean weight of 0.102 ± 0.015 g, a polyphenol content of approximately 160 μg/unit, disintegration time of <45 min, and recovery of the nanosized carriers. The polyphenols were completely released from the solid forms after 8 h, although part of them remained encapsulated in the nanocapsules. This study represents a proof of concept concerning the use of semisolid extrusion to produce 3D printed forms composed of polymeric nanocapsules in a one-step process. It proposes an original platform for the development of solid nanomedicines from liquid aqueous nanocapsule suspensions.

Development and validation of a fluorimetric method to determine quassin in polymeric nanocapsule suspension

A simple, rapid, and sensitive fluorimetric method was developed and validated to quantify quassia in polymeric nanocapsule suspensions and non polymeric suspensions, using acetonitrile as a solvent. The excitation and emission wavelengths were set at 397 nm and 465 nm, respectively. The calibration graph was linear from 0.05 to 0.25 µg/mL with a correlation coefficient of 0.9892. The detection and quantitation limits were 2.4 and 0.8 µg/mL, respectively. The validation results confirmed that the developed method is specific, linear, accurate, and precise for its intended use. The current method was successfully applied to the evaluation of curcumin content in lipid and polymeric nanocapsule suspensions during the early stage of formulation development.

Ferulic acid-loaded nanocapsules: Evaluation of mucosal interaction, safety and antioxidant activity in human mononucleated cells

Ferulic acid (FA) is a phenolic compound that has antioxidant, anti-inflammatory and anticarcinogenic properties besides presenting cytoprotective activity. It has limited oral bioavailability what is a challenge to its therapeutic application. In this way, this investigation aimed to develop FA-loaded nanocapsule suspensions (NC-FA) prepared with ethylcellulose and evaluate their in vitro release profile, mucoadhesion and irritation potential; scavenging capacity, cytotoxicity, cytoprotection and genoprotection against hydrogen peroxide-induced damage in hMNC (human Mononucleated Cells) culture. The nanocapsules presented physicochemical characteristics compatible with colloidal systems (NC-FA: 112 ± 3 nm; NC-B (without FA): 107 ± 3 nm; PdI < 0.2; Span<2.0 and negative zeta potential). In addition, the nanoparticulate system promoted the FA controlled release, increasing the half-life twice through the in vitro dialysis method. NC-FA and NC-B were able to interact with mucin, which is an indicative of mucoadhesive properties and the association of FA with nanocapsules showed decreased irritation by HET-CAM method. Besides, the NC-FA did not present cytotoxicity in hMNC and improved the ATBS radical scavenging capacity. Besides, it prevented, treated and reversed oxidative conditions in a H2O2-induced model in hMNC. Thus, this nanocarrier formulation is promising to perform more preclinical investigations focusing on diseases involving oxidative mechanisms.

Mucoadhesive gellan gum hydrogel containing diphenyl diselenide-loaded nanocapsules presents improved anti-candida action in a mouse model of vulvovaginal candidiasis

The aim of this study was to evaluate the in vitro antifungal action of a diphenyl diselenide-loaded poly(ε-caprolactone) nanocapsules suspension (NC-1) and incorporate it into a gellan gum hydrogel formulation in order to assess its in vivo efficacy in an animal model of vulvovaginal candidiasis. Nanocapsules suspensions containing the compound (NC-1 ∼ 5 mg/mL) or not (NC-B) were prepared by the interfacial deposition of preformed polymer method. To estimate in vitro antifungal effect, the broth microdilution test was applied. The results showed that NC-1 had equal or lower MIC values when compared to free compound against fifteen Candida strains. Following, the hydrogel was prepared by direct thickening of the nanocapsules suspension by gellan gum addition. The animal model of vulvovaginal candidiasis was induced by infecting female Swiss mice with Candida albicans strains. The animals were topically treated with 20 µL of hydrogels (NC-1 and free compound - 0.1 mg of diphenyl diselenide/once a day for seven days) and then the total fungal burden was assessed after the euthanasia. The results showed that the hydrogels presented pH in the acidic range, compound content close to theoretical value, homogeneous particle distribution with nanometric size, high physicochemical and microbiological stability as well as great bioadhesive property. The nano-based presented superior pharmacological action in comparison to the hydrogel containing non-encapsulated diphenyl diselenide. The results demonstrated that the nanoencapsulation maintained the effective antifungal action of diphenyl diselenide. The nano-based hydrogel formulation may be considered a promising approach against vulvovaginal candidiasis.

Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing

The skin aging process in women is accelerated due to decreases in serum estrogen levels triggered by the menopause process. Hence, poly(L-lactic acid) lipid-core nanocapsules containing ursolic acid (NPLA-UA) were developed using the interfacial deposition of the preformed polymer methodology as a strategy to reduce damages to the healing process caused by hormonal deficiency in ovariectomized rats. The colloidal suspensions of nanocapsules presented adequate size and morphology (254 and 375 nm), negative zeta potential (-31 and −37 mV), high encapsulation efficiency (99.89 %), and amorphous character.The analyses performed in an in vivo healing trial showed that the treatment with NPLA-UA resulted in faster wound retraction with less inflammatory response. In addition, the angiogenic process was stimulated increased synthesis of dermal collagen occurred. Ursolic acid-loaded, lipid-core nanocapsules are suitable for treating skin changes triggered by decreased estrogen in menopause.

Development of a nanotechnological-based hydrogel containing a novel benzofuroazepine compound in association with vitamin E: An in vitro biological safety and photoprotective hydrogel

This study aimed to evaluate the potential DNA photoprotection of nano-based hydrogels containing a novel benzofuroazepine molecule. Photoprotective property of three benzofuroazepine derivative compounds was assessed by determining a UV light absorptive profile. Nanocapsule suspensions (Eudragit® RS 100 as polymeric wall and medium-chain triglyceride or vitamin E as oil core) containing the benzofuroazepine compound that had the best UV spectral absorption were developed and physicochemically characterized. Photostability assay, bioadhesive property as well as preliminary toxicity parameters (HET-CAM and Artemia salina lethality assays) for free or nanoencapsulated forms were assessed. Among the molecules, the UV absorbance spectrum of free MBBA showed a broad and high intensity absorbance at UVB and UVA ranges. MBBA-nanocapsule suspensions had nanometric and homogeneous size distribution, bioadhesiveness property, and increased the UV light scattering in comparison to the free compound. Besides, all formulations triggered no irritative responses and the nanoencapsulation mitigated the toxic effect to Artemia salina observed to free MBBA. Following, hydrogels were prepared by thickening nanocapsule suspensions with gellan gum and their DNA photoprotection properties were determined by the exposure of DNA samples to the UVB and UVA radiation. Hydrogels showed acid pH values, compound content close to the theoretical value (3 mg/g), particle size in nanometric range, and spreadability profile suitable for cutaneous application. All MBBA hydrogels were effective against photoproducts formation induced by UVB and UVA radiation. In conclusion, these data show the identification of a compound with promising UV absorptive potential and the preparation of a final nano-based hydrogel for cutaneous application.

Incorporation of nanocapsules into gellan gum films: A strategy to improve the stability and prolong the cutaneous release of silibinin

This study aimed to develop gellan gum films containing silibinin-loaded nanocapsules as a novel approach for cutaneous administration of this flavonoid. The nanocapsule suspensions were prepared and presented mean size around 140 nm with homogenous distribution, negative zeta potential and silibinin encapsulation efficiency close to 100%. Then, these suspensions were converted into gellan gum films by solvent casting method. The films were transparent, flexible and maintained the gellan gum hydrophilicity. Nanocapsules provided the silibinin homogenous distribution in the films and prolonged its release, as well as improved the gellan gum occlusion potential. Besides, the nanosuspensions conversion into films improved the silibinin stability. Additionally, the nano-based films presented a swelling index 1.5 times higher than films containing non-nanoencapsulated silibinin. Microscopic analysis evidenced the homogeneous surface of the nano-based films, while films containing non-nanoencapsulated silibinin presented small cracks. The in vitro skin permeation profile confirmed the silibinin gradual release from the nano-based films and its greater retention in the dermis when the skin is damaged. Finally, the formulations presented no irritant effect in the HET-CAM assay. Therefore, the conversion of silibinin-loaded nanocapsule suspensions into films might be considered a promising platform for skin delivery of this flavonoid.

Nanoencapsulation potentiates the cutaneous anti-inflammatory effect of p,p′-methoxyl-diphenyl diselenide: Design, permeation, and in vivo studies of a nanotechnological-based carrageenan gum hydrogel

This study aimed to investigate the feasibility of preparing a hydrogel based on (OMePhSe)2-loaded poly(Ɛ-caprolactone) nanocapsules using carrageenan gum as a gel-forming agent. Furthermore, the anti-inflammatory action of hydrogel was assessed in an animal model of skin lesion induced by ultraviolet B (UVB) radiation in mice. Nanocapsules were prepared using the interfacial deposition of preformed polymer technique. The hydrogels were obtained by the direct addition of nanocapsules suspension in carrageenan gum (3%). Formulations with free compound, vehicle, and blank nanocapsules were also produced. The hydrogels were characterized by pH, compound content, diameter, spreadability, rheological behavior, and permeation profile. The pharmacological performance was assessed in an animal model of skin injury induced by UVB-radiation in male Swiss mice. All hydrogels had pH around 7.0, compound content close to the theoretical value (2.5 mg/g), an average diameter in nanometric range (around 350 nm), non-Newtonian flow with pseudoplastic behavior, and suitable spreadability factor. The nano-based hydrogel increased the compound content in the epidermis and dermis layers in comparison to the formulation prepared with non-encapsulated (OMePhSe)2. Stability studies revealed that the hydrogels of nanoencapsulated compound had superior physicochemical stability in comparison to the formulation of free (OMePhSe)2. Moreover, topical treatment with the hydrogel containing (OMePhSe)2 loaded-nanocapsules was more effective in reducing ear thickness and the inflammatory process induced by UVB radiation in mice. Herein, a polysaccharide was applied as a gel-forming agent using a simple and low-cost method. Besides, a superior permeation profile and improved pharmacological action were achieved by the compound encapsulation.

Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells.

Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (−33 to −41 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer.