•Lipid nanoparticles increased the retained amount of drug into the skin.•The enhancing effect of penetration was also dependent on oleic acid concentration.•Lipid nanoparticles were ...biocompatible.•NLC presented potent antitumoral effect.•The presence of oleic acid in the NLC seems to potentialize the antitumoral effect.
The objective of this study was to develop and characterize lipid nanoparticles (LNs) containing chloroaluminum phthalocyanine (ClAlPc) to reduce the aggregation of the drug and improve its skin penetration and its antitumor effect. LNs were prepared and characterized by using stearic acid (SA) as solid lipid and oleic acid (OA) as liquid lipid in different proportions. in vitro and in vivo skin penetration was evaluated using modified Franz diffusion cells and fluorescence microscopy, respectively. in vitro biocompatibility and Photodynamic Therapy (PDT) were performed using L929-fibroblasts cell line and A549 cancer cell line and melanoma BF16-F10, respectively. OA promoted the increase in the encapsulation efficiency and drug loading, reaching values of 95.8% and 4%, respectively. The formulation with 40% OA (NLC 40) showed a significantly higher (p < 0.01) amount of drug retained in the skin compared to other formulations. All formulations developed were considered biocompatible. PDT evidenced the antitumor efficacy of NLC 40 with reduced cell viability for approximately 10% of cancer cells, demonstrating that the presence of OA in the NLC seems to potentialize this antitumor effect. PDT in BF16-F10 melanoma using NLC 40 resulted in a reduction in mean cell viability of approximately 99%. According to the results obtained, the systems developed may be promising for the incorporation of ClAlPc in the treatment of skin cancer by photodynamic therapy.
•Cinnamomum essential oil from bark (CZEO_B) was the most effective essential oil.•Microemulsion (ME) containing CZEO_B and Olivem 300 was obtained.•Synergism between Olivem 300 and CZEO_B was ...observed in the ME.•ME was also able to significantly decrease the cytotoxicity of CZEO_B.•ME containing Olivem 300 and CZEO_B can be a promising formulation for skin lightening.
The present work aimed to develop and characterize a microemulsion containing an essential oil with potential skin-lightening activity. Initially, Cinnamomum zeylanicum Blume essential oils (CZEO) extracted from bark and leaf, and the essential oils of Citrus sinensis and Syzygium aromaticum, were characterized and the tyrosinase inhibitory activity was determined. Thereafter, microemulsions were obtained through the Pseudoternary Phase Diagram using a mixture of Tween 80®: Propylene glycol (2:1) as surfactant and co-surfactant, respectively, Olivem 300® as oily phase and water as aqueous phase. The CZEO from the bark showed higher tyrosinase inhibitory activity and was incorporated into the selected microemulsions: one o/w microemulsion (B7) and three bicontinuous microemulsions (B5, B6 and C6). Microemulsion B5 was able to incorporate a greater amount of essential oil and the tyrosinase inhibitory activity of this formulation was determined. Microemulsions with and without the essential oil were isotropic with a droplet diameter lower than 60 nm and Newtonian behavior. Microemulsion B5 showed significant greater tyrosinase inhibition activity and lower cytotoxicity than did the isolated oil. According to the results, the microemulsions containing the CZEO obtained from the bark may be promising in formulations for skin lightening using natural active agents.
This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using ...α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
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•Microemulsions (ME) containing α-bisabolol presented antileishmanial activity.•ME showed a 2.5-fold increase in the permeation of α-bisabolol.•ME showed greater activity against promastigote and amastigote than α-bisabolol.•F5E25 ME showed IC50 of 3.37 μg. mL−1, 50 times lower than α-bisabolol.•F5E25 ME presented high SI, approximately 15.
Lipid nanoparticles, both solid lipid nanoparticles and nanostructured lipid carriers (NLC), containing tacrolimus (FK) were obtained by solvent diffusion method associated with ultrasonication using ...stearic acid (SA) or beeswax as solid lipid. The oleic acid was used as liquid lipid in the NLC. Lipid nanoparticles were characterized by determining the drug loading, particle size, polydispersity index (PDI) and zeta potential (ZP). Analysis by differential scanning calorimetry and X-ray diffraction were performed. Lipid nanoparticles presented nano-sized from 139 to 275 nm. The PDI results show the particles present from 0.3 to 0.5, and ZP was higher than |25| mV. Drug loading ranged of 2.3–3.2%. SA nanoparticles presented better ZP, average size and distribution. However, beeswax nanoparticles showed higher drug loading. Results suggest there are no incompatibilities between FK and the raw materials. Polymorphic modifications were not observed. The results presented show that lipid nanoparticles using both lipids were successfully obtained and may represent promising delivery system of FK in topical formulations.
Supra-amphiphiles are a new class of building blocks that are fabricated by means of noncovalent forces. In this work, we studied the formation of supra-amphiphiles by combining hydrophilic meglumine ...(MEG) with hydrophobic maleated castor oils (MACO). Spectroscopic analysis demonstrated that ionic interactions are the main driving force in the fabrication of these materials. Subsequently, supra-amphiphile/water systems were examined for their structure and water behavior by polarized optical microscopy (POM), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). Micellar and lamellar liquid crystalline phases were observed. Finally, we observed that the supra-amphiphiles produced using an excess of MEG retain a large amount of water. As bound water plays an important role in biointerfacial interactions, we anticipate that these materials will display a pronounced potential for biomedical applications.
Supramolecular gels are soft materials formed mainly by low molecular weight units held together by intermolecular interactions. Stabilizing these kinds of materials is quite a challenge due to the ...influence of multiple factors interfering with the integrity of the supramolecular structure. In our previous studies, we have shown that the aminocarbohydrate meglumine (MEG) interacts with organic acids by ion-pairing leading to the formation of MEG–carboxylate adducts. These adducts undergo supramolecular polymerization by heat treatment, but the macromolecular assembly was stable for a short period due to hydrogen bond (H-bond) breakup. Herein, we attempt to study the influence of hydrophobic building blocks on the formation of these compounds aiming to stabilize H-bonds to produce polymerizable supra-amphiphiles in water. Oleic acid and stearic acid are two analogous fatty acids differing only in the presence of unsaturation that were used in our studies. Results demonstrated that the presence of unsaturation hinders gelation in water by interfering with the self-assembly behavior of supra-amphiphiles. Thus, unsaturated supra-amphiphiles behave like traditional surfactants and gelify water at high concentrations (above 30% w/w). On the other hand, supramolecular gels with a polymer-like behavior could be produced with a saturated supra-amphiphile in water (above 4% w/w). The material was characterized by a lamellar arrangement that facilitates the alignment of H-bonds necessary to stabilize the self-assembled structure. These results have pivotal importance on the design of polymerizable supra-amphiphiles and demonstrate that the double bond of hydrophobic building blocks is an important design factor to be considered by scientists studying similar materials.
Objectives Zidovudine is the antiretroviral drug most frequently used for the treatment of AIDS. Although its effectiveness is recognized, it undergoes extensive first‐pass metabolism and exhibits ...poor oral bioavailability. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first‐pass effect. There are some mechanisms that limit intranasal absorption, such as mucociliary clearance, which rapidly removes the formulation from the nasal cavity. To improve the nasal residence time of zidovudine on the nasal mucosa, we aimed to develop a mucoadhesive surfactant system for zidovudine nasal administration.
Methods Systems composed of PPG‐5‐CETETH‐20 as surfactant, oleic acid and water were characterized by polarized light microscopy, small‐angle X‐ray scattering and rheological measurements. Mucoadhesion was investigated by phase behaviour studies, rheological synergism and mucoadhesive strength determination.
Key findings Results indicate that the original formulations were microemulsions that displayed phase transition to a lamellar phase when brought into contact with aqueous nasal simulated mucus. The phase transition was accompanied by an increase in system elasticity and, irrespective of phase behaviour, all the systems showed a good mucoadhesive force. Thus, a viscous and mucoadhesive liquid crystalline matrix could be formed when the formulations were in contact with simulated mucus, which may prolong the residence time of zidovudine in the nasal cavity.
Conclusions These findings indicate a potentially useful system for nasal administration of zidovudine.
Zidovudine (AZT) and lamivudine (3TC) are drugs commonly used in the treatment of acquired immune deficiency syndrome; however, these drugs have low bioavailability and short biological half-life. ...These factors contribute to the emergence of various side effects and lack of patient adherence to treatment. Therefore, the study of drug delivery systems is of extreme interest. In this context, this study intends to develop hydroxypropylmethylcellulose films (HPMC) containing AZT and films containing 3TC, and assess the existence of drug/polymer interactions by means of thermal analysis techniques differential scanning calorimetry (DSC) and thermogravimetry (TG)/derivative TG (DTG), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD), contributing to the optimization of antiretroviral therapy. The films produced showed drying uniformity and drug distribution. DSC curves indicated that these drugs may be in an amorphous form dispersed in the polymeric matrix. Thermal decomposition profiles obtained in the TG/DTG studies of films containing drugs showed similarities with the curves of their respective physical mixtures. The FTIR spectra showed the characteristic bands conservation of AZT and 3TC isolated in the films with drugs. The results indicate that these drugs did not undergo a process of degradation or chemical interaction with the polymer that would lead to the modification or alteration of their chemical structures. XRD studies confirmed that these drugs were homogenously dispersed in the polymeric matrix. These results also showed that there was no drug/polymer incompatibility in HPMC films.
Solid lipid nanoparticles (SLN) without drug and SLN loaded with chloroaluminum phthalocyanine (AlClPc) were prepared by solvent diffusion method in aqueous system and characterized by thermal ...analyses and X-ray diffraction (XRD) in this study. Determination of particle size, zeta potential (ZP), and encapsulation efficiency were also evaluated. SLN containing AlClPc of nanometer size with high encapsulation efficiency and ZP were obtained. The results indicated that the size of SLN loaded with AlClPc is larger than that of the inert particle, but ZP is not changed significantly with incorporation of the drug. In differential scanning calorimetry (DSC) curves, it was observed that the melting point of stearic acid (SA) isolated and in SLN occurred at 55 and 64 °C, respectively, suggesting the presence of different polymorphs. DSC also shows that the crystallinity state of SLN was much less than that of SA isolated. The incorporation of drug in SLN may have been favored by this lower crystallinity degree of the samples. XRD techniques corroborated with the thermal analytic techniques, suggesting the polymorphic modifications of stearic acid.
Antimicrobial resistance is a current public health concern, limiting the available therapeutic options used for the treatment of common bacterial infections. The development of new drug entities via ...biotechnological processes is however expensive and time-consuming. Therefore, old antimicrobial agents have been recovered for clinical use. An example of these drugs is polymyxin, which is known for its serious adverse side effects, such as nephrotoxicity, neurotoxicity and promotion of skin pigmentation. To overcome these limitations, the use of biodegradable nanoparticles has been proposed to allow site-specific targeting, increasing the drug's bioavailability and decreasing its side effects. The aim of this work was the development of an optimized pharmaceutical formulation composed of solid lipid nanoparticles (SLN) loading polymyxin B sulphate (PLX) for the treatment of bacterial infections. The PLX-loaded SLN were produced by a double emulsion method (w/o/w), obtaining particles with a mean size of approximately 200nm, polydispersity of 0.3 and zeta potential of −30mV. The encapsulation efficiency reached values above 90% for all developed formulations. SLN remained stable for a period of 6months of storage at room temperature. The occlusive properties of the SLN was shown to be dependent on the type of lipid, while the antimicrobial properties of PLX-loaded SLN were effective against resistant strains of Pseudomonas aeruginosa. Results from the differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and small angle X-ray scattering (SAXS) analyses confirmed the crystallinity of the inner SLN matrices, suggesting the capacity of these particles to modify the release profile of the loaded drug.
PLX-loaded SLN produced by a double emulsion method (w/o/w), obtaining unilamelar versus multilamelar particles with a crystalline matrix confirmed by X-ray diffraction. Display omitted
