Lipid-Based Nanosystems for the Topical Application of Ferulic Acid: A Comparative Study

In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Ad-ditionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses sug-gest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O3 exposur

Energy requirements for pregnant dairy cows.

This study aimed to estimate energy requirements of pregnant Holstein × Gyr cows. Different planes of nutrition were established by two feeding regimens: ad libitum or maintenance. Sixty-two nonlactating cows with average body weight of 480 ± 10.1 kg and an age of 5 ± 0.5 years were used. Cows were divided into three groups: pregnant (n = 44), non-pregnant (n=12), and baseline reference (n = 6). The 56 pregnant and non-pregnant cows were randomly allocated into a feeding regimen: ad libitum or maintenance. To evaluate the effects of days of pregnancy, pregnant and non-pregnant animals were slaughtered at 140, 200, 240, and 270 days of pregnancy. Energy requirements for maintenance differed between pregnant and non-pregnant cows, thus two equations were developed. Net energy and metabolizable energy requirements for maintenance of non-pregnant cows were 82 kcal/kg empty body weight0.75/day and 132 kcal/kg empty body weight0.75/day, respectively. The efficiency of use of metabolizable energy for maintenance of non-pregnant cows was 62.4%. Net energy and metabolizable energy for maintenance of pregnant cows were 86 kcal/kg empty body weight0.75/day and 137 kcal/kg empty body weight0.75/day, respectively. Efficiency of use of metabolizable energy for maintenance of pregnant cows was 62.5%. The efficiency of use of metabolizable energy for gain was 41.9%. The efficiency of use of metabolizable energy for pregnancy was 14.1%. Furthermore, net energy requirement for pregnancy was different from zero from day 70 of pregnancy onwards. In conclusion, net energy and metabolizable energy requirements for maintenance of non-pregnant cows are different from pregnant cows. Furthermore, we believe that the proposed non-linear equations to estimate net energy requirements for pregnancy are more adequate than current NRC equation, and should be recommended for Holstein × Gyr cows

Liposomal and ethosomal gels: from design to application

editoria

Production and characterization of clotrimazole liposphere gel for candidiasis treatment

This study describes the design and characterization of a liposphere gel containing clotrimazole for the treatment of Candida albicans. Lipospheres were produced by the melt-dispersion technique, using a lipid phase constituted of stearic triglyceride in a mixture with caprylic/capric triglyceride or an alkyl lactate derivative. The latter component was added to improve the action of clotrimazole against candida. The liposphere morphology and dimensional distribution were evaluated by scanning electron microscopy. Clotrimazole release kinetics was investigated by an in vitro dialysis method. An anticandidal activity study was conducted on the lipospheres. To obtain formulations with suitable viscosity for vaginal application, the lipospheres were added to a xanthan gum gel. The rheological properties, spreadability, leakage, and adhesion of the liposphere gel were investigated. Clotrimazole encapsulation was always over 85% w/w. The anticandidal study demonstrated that the encapsulation of clotrimazole in lipospheres increased its activity against Candida albicans, especially in the presence of the alkyl lactate derivative in the liposphere matrix. A dialysis method demonstrated that clotrimazole was slowly released from the liposphere gel and that the alkyl lactate derivative further controlled clotrimazole release. Adhesion and leakage tests indicated a prolonged adhesion of the liposphere gel, suggesting its suitability for vaginal application

Lipid-based nanosystems as a tool to overcome skin barrier.

Skin may be affected by many disorders that can be treated by topical applications of drugs on the action site. With the advent of nanotechnologies new efficient delivery systems have been developed. Particularly, lipid-based nanosystems such as liposomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers, cubosomes and monoolein aqueous dispersions, have been proposed for cutaneous application, reaching in some cases the market or clinical trials. This review aims to provide an overview of the different lipid-based nanosystems, focusing on their use for topical application. Particularly, the description of biocompatible nanosystems able to dissolve lipophilic compounds and to control the release of carried drug possibly reducing side effects is outlined. Notably, the rationale to topically administer antioxidant molecules by lipid nanocarriers is described. Indeed, the structural similarity between the nanosystem lipid matrix and the skin lipids allows the achievement of a transdermal effect. Surely more research is required to better understand the mechanism of interaction between li-pid-based nanosystems and skin. However, this attempt to summarize and highlight the possibilities offered by lipid-based nanosystems could help the scientific community to take advantage of the benefits derived from this kind of nanosystem

Lipid nanostructures for antioxidant delivery: a comparative preformulatory study

This investigation aims to generate new lipid nanoparticles for cutaneous antioxidant delivery. Indeed, several molecules, such as α-tocopherol and retinoic acid, have been shown to improve skin condition and even counteract the effects of exogenous challenges such as smoking on skin aging. Particularly solid lipid nanoparticles and nanostructured lipid carriers have been investigated. Solid glyceride lipids, such as tristearin, precirol, compritol and suppocire have been employed in the absence and in the presence of miglyol. A comparative study has been conducted in order to evaluate the effect of different lipid compositions on presence of agglomerates, dimensional distribution, morphology and encapsulation efficiency of lipid nanoparticles. After production of nanoparticles by ultrasound homogenization, their dimensional distribution was measured by photon correlation spectroscopy and evaluated until 90 days from production. Since nanostructured lipid carriers enabled to reduce the agglomerate formation and to control their dimensional stability with respect to solid lipid nanoparticles, they have been selected for antioxidant encapsulation. Once nanostructured lipid carriers have been produced in the presence of α-tocopherol and retinoic acid, their external and inner structure have been characterized by cryogenic transmission electron microscopy and x-ray spectroscopy respectively. Antioxidant encapsulation efficiency was evaluated by HPLC upon disaggregation of nanostructured lipid carriers. Apart from suppocire, that lead to formation of spherical vesicles, the other lipids resulted in irregular shaped nanoparticles. A doubling in the lipid phase amount enabled to double the α-tocopherol loading within the nanoparticles, controlling the drug stability up to 3 months. To evaluate the protective properties of the nanostructured lipid carriers loaded with α-tocopherol, human skin explants pretreated with nanostructures were exposed to cigarette smoke, afterwards protein levels of the stress inducible enzyme heme oxygenase were analyzed in skin homogenates. Interestingly, it was found that the pretreatment avoided heme oxygenase upregulation, suggesting a protective effect of the nanoparticles

Nanomedicines to treat skin pathologies with natural molecules

The skin and mucous membranes are subjected to many disorders and pathological conditions. Nature offers a wide range of molecules with antioxidant activity able to neutralize, at least in part, the formation of free radicals and therefore to counteract the phenomena of cellular aging. Since synthetic drugs for the treatment of skin diseases can induce resistance, it is particularly interesting to use compounds of plant origin, transporting them in pharmaceutical forms capable of controlling their release and absorption. This review provides an overview of new findings about the use of lipid-based nanosystems for the delivery of natural molecules useful on the topical treatment of skin disorders. Several natural molecules encapsulated in lipid nanosystems have been considered in the treatment of some skin pathologies or diseases. Particularly, the use of rosemary and eucalyptus essential oil, saffron derivatives, curcumin, eugenol, capsaicin, thymol and lycopene has been reported. The molecules have been alternatively encapsulated in viscous systems, such as the organogels, or in liquid systems, such as ethosomes, transferosomes, solid lipid nanoparticles and monoolein based dispersions thickened by inclusion in carbomer gels. The nanostructured forms have been in vitro and in vivo investigated for the treatment of skin disorders due to dehydration, inflammation, melanoma, wound healing, fungal infections or psoriasis. The data reported in the different studies have suggested that the cutaneous application of lipid nanosystems allows a deep interaction between lipid matrix and skin strata, promoting a prolonged release and efficacy of the loaded natural molecules. This review suggests that the application of natural molecules onto the skin by lipid-based nanosystems can provide numerous clinician benefits in dermatology and cosmetics

Manganese in diagnostics: A preformulatory study

This investigation aims to find out lipid-based nanosystems as a tool to deliver manganese for diagnostic purpose in multimodal imaging techniques. Particularly, the study describes the production and characterization of aqueous dispersions of anionic liposomes, as delivery systems for two model manganese-based compounds, namely manganese chloride and manganese acetylacetonate. Negatively charged liposomes were obtained using four different anionic surfactants, namely sodium docusate (SD), N-lauroylsarcosine (NLS), Protelan AG8 (PAG) and sodium lauroyl lactylate (SLL). Liposomes were produced by direct hydration method followed by extrusion and characterized in terms of size, polydispersity, surface charge and stability over time. After extrusion, liposomes are homogeneous and monodispersed with an average diameter not exceeding 200 nm and a negative surface charge as confirmed by ζ potential measurement. Moreover, as indicated by atomic absorption spectroscopy analyses, the loading of manganese-based compounds was almost quantitative. Liposomes containing NLS or SLL were the most stable over time and the presence of manganese-based compounds did not affect their size distribution. Liposomes containing PAG and SD were instable and therefore discarded. The in vitro cytotoxicity of the selected anionic liposomes was evaluated by MTT assay on human keratinocyte. The obtained results highlighted that the toxicity of the formulations is dose-dependent

L-dopa co-drugs in nanostructured lipid carriers: a comparative study

This paper describes the production and characterization of nanostructured lipid carriers (NLC) containing four different levodopa (LD) co-drugs (PD), named PDA (3,4-diacetyloxy-LD-caffeic acid co-drug), PDB (lipoic aciddopamine co-drug), PDC (lipoic acid-3,4-diacetoxy-dopamine co-drug), and PDD(dimeric LDco-drug containing an alkyl linker),with therapeutic potential in Parkinson's disease. These co-drugswere producedwith the aimof prolonging the pharmacological activity of LD, enhancing its absorption and protecting it frommetabolism. These compoundswere characterized by very lowwater solubility that limits their systemic administration. To improve the solubility of these LDPD, NLC were considered. The obtained NLC showed acceptable particle size and a good stability up to two months from preparation. Cryo- TEM morphological characterization revealed no substantial differences between unloaded and co-drug loaded NLC. In vitro studies showed that the LDPD loaded NLC provided a controlled drug release. Moreover, the enhancement of LDPD stability on the hydrolysis catalysed by foetal calf serum (FCS) esterases or in the presence of lipases was evaluated as compared to a labrasol solution. In presence of esterases PDA-NLC and PDD-NLC showed half-lives higher N3-fold as compared to the corresponding aqueous micellar solution. In the case of PDB-NLC it was found that the stability exceeds the 19 h. It can be concluded that NLC represent good strategies to encapsulate lipophilic LD co-drugs, although further studies aimed to deeply evaluate anti-parkinsonian effects in vivo have to be carried on

Antisense oligonucleotides conjugated with lipophilic compounds: synthesis and in vitro evaluation of exon skipping in duchenne muscular dystrophy

Our groups previously reported that conjugation at 3′-end with ursodeoxycholic acid (UDCA) significantly enhanced in vitro exon skipping properties of ASO 51 oligonucleotide targeting the human DMD exon 51. In this study, we designed a series of lipophilic conjugates of ASO 51, to explore the influence of the lipophilic moiety on exon skipping efficiency. To this end, three bile acids and two fatty acids have been derivatized and/or modified and conjugated to ASO 51 by automatized solid phase synthesis. We measured the melting temperature (Tm) of lipophilic conjugates to evaluate their ability to form a stable duplex with the target RNA. The exon skipping efficiency has been evaluated in myogenic cell lines first in presence of a transfection agent, then in gymnotic conditions on a selection of conjugated ASO 51. In the case of 5′-UDC-ASO 51, we also evaluated the influence of PS content on exon skipping efficiency; we found that it performed better exon skipping with full PS linkages. The more efficient compounds in terms of exon skipping were found to be 5′-UDC- and 5′,3′-bis-UDC-ASO 51