Novel radioiodinated desvenlafaxine-loaded lipid nanocapsule for brain delivery.

Lipid nanocapsules (LNCs) are lipid nanocarriers developed for drug delivery enhancement. The antidepressant drug desvenlafaxine (DSV) was entrapped in LNC to improve its brain delivery. Different DSV-loaded LNCs formulae using different oils and surfactants were studied to obtain the optimum formula for further studies. In vivo biodistribution studies were done using Swiss albino mice by intravenous injection of DSV-loaded LNCs by radioiodination technique. The optimum DSV-loaded LNC formula was obtained by using Labrafil® M1944CS as the oil and Solutol® HS15 as the surfactant in the ratio of 1:1, with a particle size of 34.28 ± 0.41 nm, a polydispersity index of 0.032 ± 0.05, a zeta potential of -25.77 ± 1.41, and good stability for up to 6 months. The in vivo biodistribution and pharmacokinetics data ensure the bioavailability improvement for DSV brain delivery as Cmax and AUC(1-t) increased more than double for intravenously DSV-loaded LNCs compared with the DSV solution. In conclusion, the results obtained from this study give an insight into the great potential of using DSV-loaded LNC for the enhancement of brain delivery.

Polymeric Nanoparticles' Accumulation in Atopic Dermatitis: Clinical Comparison between Healthy, Non-Lesional, and Lesional Skin.

A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin.

The interplay of solvent-drug-protein interactions during albumin nanoparticles formulations for temozolomide delivery to brain cancer cells.

OBJECTIVES: Temozolomide (TMZ), the first line for glioma therapy, suffers from stability at physiological pH. TMZ was selected as a challenging model drug for loading into human serum albumin nanoparticles (HSA NPs). Our aim is to optimise the conditions for TMZ loading into HSA NPs while ensuring TMZ stability. METHODS: Blank and TMZ-HSA NPs were fabricated using the de-solvation technique and the effect of different formulation parameters was evaluated. KEY FINDINGS: For blank NPs, crosslinking time had no significant effect on NPs' size while acetone produced significantly smaller particles than ethanol. Upon drug loading, though TMZ was stable in acetone and ethanol as single agents yet, ethanol-based NPs showed misleadingly high EE% due to drug instability in ethanol formulations as evident by the UV spectrum.The optimum conditions for drug-loaded particles were: 10 mg/ml HSA, 4 mg TMZ using acetone, yielded NPs with 145 nm in diameter, ξ of -16.98 mV and 0.16% DL. The selected formula reduced the cell viabilities of GL261 glioblastoma cells and BL6 glioblastoma stem cells to 61.9% and 38.3%, respectively. CONCLUSIONS: Our results corroborated that careful manipulation of TMZ formulation processing parameters is crucial for encapsulating such chemically unstable dug while simultaneously ensuring its chemical stability.

Can Essential Oils/Botanical Agents Smart-Nanoformulations Be the Winning Cards against Psoriasis?

Although psoriasis remains one of the most devastating inflammatory disorders due to its huge negative impact on patients' quality of life, new "green" treatment approaches still need to be fully explored. The purpose of this review article is to focus on the utilization of different essential oils and active constituents of herbal botanical origin for the treatment of psoriasis that proved efficacious via both in vitro and in vivo models. The applications of nanotechnology-based formulations which displayed great potential in augmenting the permeation and delivery of these agents is also addressed. Numerous studies have been found which assessed the potential activity of natural botanical agents to overcome psoriasis. Nano-architecture delivery is applied in order to maximize the benefits of their activity, improve properties, and increase patient compliance. This field of natural innovative formulations can be a promising tool to optimize remediation of psoriasis while minimizing adverse effects.

Boosting the In Vivo Transdermal Bioavailability of Asenapine Maleate Using Novel Lavender Oil-Based Lipid Nanocapsules for Management of Schizophrenia.

Lipid nanocapsules (LNCs) are promising for transdermal drug delivery due to their higher permeability-enhancing effects compared to polymeric nanoparticles. Lavender oil is an essential oil consisting of several terpenes (primarily linalool and linalyl acetate) known for their profound permeation-enhancing action. In the present work, we successfully encapsulated asenapine maleate (a second-generation antipsychotic that is highly metabolized by the liver, reducing its oral bioavailability) into biocompatible LNCs for transdermal application using a novel oily phase, i.e., lavender oil (LO-LNCs). A comparative study was conducted to determine the effects of different oily phases (i.e., Miglyol® 812, Labrafil® M1944CS, and Labrafac™ PG) on the LNCs. Surfactant types (Kolliphor® HS15, Kolliphor® EL and Tween80) and oil:surfactant ratios were studied. Blank and asenapine-loaded LNCs were optimized for particle size, polydispersity index, zeta potential, drug content and ex vivo skin permeation. Lavender oil and Labrafil® showed smaller vesicular sizes, while LO-LNCs increased the permeation of ASP across rat skin. In vivo pharmacokinetics revealed that LO-LNCs could increase the ASP Cmax via transdermal application by fourfold compared to oral suspension. They increased the bioavailability of ASP by up to 52% and provided sustained release for three days. The pharmacokinetic profile of the LO-LNCs was compared to ASP-loaded invasomes (discussed in a previous study) to emphasize LNCs' transdermal delivery behavior.

Lipoproteins as Drug Carriers for Cyclosporine A: Optimization of the Entrapment.

Lipoproteins are natural nanostructures responsible for the transport of cholesterol and other lipids in the blood. They are characterized by having a lipophilic core surrounded by an amphiphilic shell composed of phospholipids, cholesterol and one or more apolipoproteins. Being endogenous carriers makes them suitable for drug delivery purposes. Here, we investigate the effect of lipoproteins' intricate composition on the entrapment efficiency of a model drug "Cyclosporine A" into the different types of lipoproteins, namely, HDL, LDL and VLDL. It was observed that the protein content of the lipoproteins had the highest effect on the entrapment of the drug with a correlation coefficient of 0.80, 0.81 and 0.96 for HDL, LDL and VLDL respectively. This was even confirmed by the effect of plasma on the association rate of lipoproteins and the drug. The second effective factor is the cholesterol concentration, while triglycerides and phospholipids had a negligible effect.

Skin targeting by chitosan/hyaluronate hybrid nanoparticles for the management of irritant contact dermatitis: In vivo therapeutic efficiency in mouse-ear dermatitis model.

Irritant contact dermatitis (ICD) is an inflammatory skin condition characterized by severe eczematous lesions. Nanoparticulate drug delivery is the most predominant way to improve dermal penetration and have gained remarkable recognition for targeted delivery of therapeutic payload and reduced off-target effects. Therefore, the current work aimed to fabricate polyelectrolyte complex nanoparticles (PENPs) containing two natural biodegradable polymers namely; chitosan (CS) and hyaluronic acid (HA) to deliver the non steroidal anti-inflammatory drug etoricoxib (ETX) to the deeper skin layers to alleviate any systemic toxicity and improve its therapeutic efficacy against ICD. ETX loaded-PENPs were prepared and optimized utilizing three independent variables; CS: HA mass ratio, chitosan solution pH and molecular weight of chitosan. Following the various physicochemical optimizations, the optimum ETX-loaded PENPs formulation (N1 0.15 %) exhibited spherical nature with an average diameter of 267.9 ± 9.4 nm, Polydispersity index of 0.366 ± 0.02, and positive zeta potential (+32.9 ± 0.47 mV). The drug was successfully entrapped and the entrapment efficiency reached 95 ± 0.2 %. N1 0.15 % formula showed efficient dermal targeting by significantly enhanced percentage of ETX permeated and retained in the various skin layers in comparison to ETX conventional gel during the ex-vivo skin permeation experiments. Furthermore, N1 0.15 % exhibited superior anti-inflammatory properties in vivo compared to ETX conventional gel in dithranol induced mice ear dermatitis. Conclusively, ETX-loaded PENPs could be a promising therapeutic approach for effecient management of ICD.

Boosting the anti-inflammatory effect of self-assembled hybrid lecithin-chitosan nanoparticles via hybridization with gold nanoparticles for the treatment of psoriasis: elemental mapping and in vivo modeling.

Gold nanoparticles are a promising drug delivery system for treatment of inflammatory skin conditions, including psoriasis, due to their small size and anti-inflammatory properties. The aim of this study was to conjugate gold nanoparticles with anti-psoriatic formulations that previously showed successful results in the treatment of psoriasis (tacrolimus-loaded chitosan nanoparticles and lecithin-chitosan nanoparticles) by virtue of their surface charges, then examine whether the hybridization with gold nanoparticles would enhance the anti-psoriatic efficacy in vivo. Successful formation of gold nanoparticles was examined by elemental mapping and selected area electron diffraction (SAED). Hybrid conjugates were examined in terms of particle size and zeta potential by dynamic light scattering (DLS). Morphological features were captured by transmission electron microscope (TEM) and X-ray diffraction (XRD) analysis was conducted, as well. All characterization was conducted for the conjugated nanoparticles and compared with their bare counterparts. The in vivo results on imiquimod (IMQ)-induced mouse model showed promising anti-psoriatic effects upon application of gold conjugated tacrolimus-loaded lecithin-chitosan hybrid nanoparticles with a significant difference from the bare hybrid nanoparticles in some of the inflammatory markers. The anti-inflammatory effect of the gold conjugate was also evident by a lower spleen to body weight ratio and a better histopathological skin condition compared to other tested formulations.

A natural protein based platform for the delivery of Temozolomide acid to glioma cells.

Glioblastoma is one of the most difficult to treat cancers with poor prognosis and survival of around one year from diagnosis. Effective treatments are desperately needed. This work aims to prepare temozolomide acid (TMZA) loaded albumin nanoparticles, for the first time, to target glioblastoma (GL261) and brain cancer stem cells (BL6). TMZA was loaded into human serum albumin nanoparticles (HSA NPs) using the desolvation method. A response surface 3-level factorial design was used to study the effect of different formulation parameters on the drug loading and particle size of NPs. The optimum conditions were found to be: 4 mg TMZA with 0.05% sodium cholate. This yielded NPs with particle size and drug loading of 111.7 nm and 5.5% respectively. The selected formula was found to have good shelf life and serum stability but with a relatively fast drug release pattern. The optimized NPs showed excellent cellular uptake with âˆ¼ 50 and 100% of cells were positive for NP uptake after 24 h incubation with both GL261 and BL6 glioblastoma cell lines, respectively. The selected formula showed high cytotoxicity with Ì´ 20% cell viability at 1 mM TMZA after 72 h incubation time. Finally, the fluorescently labelled NPs showed co-localization with the bioluminescent syngeneic BL6 intra-cranial tumour mouse model after intravenous administration.

Design of long acting invasomal nanovesicles for improved transdermal permeation and bioavailability of asenapine maleate for the chronic treatment of schizophrenia.

Asenapine Maleate (ASPM) is a second generation antipsychotic used for the management of schizophrenia but with very limited oral bioavailability due to its extensive first pass metabolism. Transdermal administration of ASPM using nanocarriers like invasomes might offer an excellent alternative to its oral administration with enhanced bioavailability and a sustained action. ASPM-loaded invasomes were successfully prepared by thin film hydration technique; meanwhile the penetration enhancing effect of terpenes (cineole and limonene) was compared to hydromiscible cosolvent (Transcutol®). Soft nanovesicles containing Transcutol® displayed smaller particle sizes than invasomes containing limonene and cineole while invasomes showed higher efficiency to encapsulate asenapine. Ex- vivo skin permeation revealed that invasomes with limonene are more efficient than those with cineole for the transdermal delivery of asenapine. The optimum nano-invasomes formulation contained 1% Limonene and showed particle size of 82 ± 0.6 nm, entrapment efficiency of 56.6 ± 1.5 % and transdermal flux of 3401.6 ± 604.2 (µg/h.cm2). Transmission electron microscopy of the selected formulation showed uniform spherical vesicles with intense outline and lighter core and FTIR study emphasized that ASPM was completely incorporated within the vesicles. The in- vivo pharmacokinetic study revealed that transdermal invasomes achieved 2 folds higher Cmax compared to oral suspension and delayed the Tmax from 1.5 h to around 4 h. The bioavailability of asenapine loaded invasomes after transdermal application was significantly improved to 54.5% compared to the 3.6 % achieved with the oral administration and exceeding the bioavailability of sublingual tablets currently available in the market and exhibited sustained release kinetics over 72 h which permits reduction of dosing frequency to increase patient adherence to medication.

Self-assembled tacrolimus-loaded lecithin-chitosan hybrid nanoparticles for in vivo management of psoriasis.

Lecithin-chitosan hybrid nanoparticles are emerging as a promising nanocarrier for topical drug delivery. They could achieve a maximized encapsulation of hydrophobic drugs due to the lipophilic nature of lecithin that comprises the core while enhancing retention in the upper skin layers using the positively charged polymeric coat of chitosan. The aim of this study is to incorporate tacrolimus; a hydrophobic anti-proliferative agent into lecithin chitosan hybrid nanoparticles by ethanolic injection technique using a suitable co-solvent to enhance encapsulation of the drug and allow a satisfactory release profile in the upper skin layers. Tacrolimus was successfully incorporated into the synthesized particles using olive oil and Tween 80 as co-solvents, with particle size (160.9 nm ± 15.9 and 118.7 nm ± 13.3, respectively) and EE (88.27% ± 4.3 and 66.72% ± 1.8, respectively). The in vitro drug release profile showed a faster release pattern for the Tween 80-containing particles over a 48-hour period (79.98% vs. 35.57%), hence, were selected for further investigation. The hybrid nanoparticles achieved significantly higher skin deposition than the marketed product (63.51% vs. 34.07%) through a 24-hour time interval, particularly, to the stratum corneum and epidermis skin layers. The in vivo results on IMQ-mouse models revealed superior anti-psoriatic efficacy of the synthesized nanoparticles in comparison to the marketed product in terms of visual observation of the skin condition, PASI score and histopathological examination of autopsy skin samples. Additionally, the in vivo drug deposition showed superior skin deposition of the nanoparticles compared to the marketed product (74.9% vs. 13.4%).

Tacrolimus-loaded chitosan nanoparticles for enhanced skin deposition and management of plaque psoriasis.

Tacrolimus is a natural macrolide that exhibits an anti-proliferative action by T-lymphocytic cells inhibition. Hence, it was tested as a potential topical treatment to improve and control psoriatic plaques. In this study, for the first time the lipophilic tacrolimus in chitosan nanoparticles was used to achieve the desired response and dermal retention of the drug using a modified ionic gelation technique. The hydrophobic drug, tacrolimus, was successfully encapsulated into the synthesized positively-charged particles (140.8 nm ± 50.0) and EE of (65.5% ± 1.3). Local skin deposition of the drug was significantly enhanced with 82.0% ± 0.6 of the drug retained in the skin compared to 34.0% ± 0.9 from tarolimus® ointment. An outstanding response to the prepared formula was the enhanced hair growth rate in the treated animals, which can be considered an excellent sign of the skin recovery from the induced psoriatic plaques after only three days of treatment.

Amelioration of murine experimental colitis using biocompatible cyclosporine A lipid carriers.

Lipoproteins are biodegradable and biocompatible natural carriers that can be utilized for the transport of hydrophobic drugs, such as cyclosporin A (CycloA), a calcineurin inhibitor utilized for the inflammatory bowel disease, such as ulcerative colitis. A major limitation in the drug treatment of inflammatory bowel disease is the inability to deliver the drug selectively toward the inflamed tissues. Nanotechnology-based drug delivery systems have led to an amelioration of the therapeutic selectivity, but still the majority of the entrapped drug is eliminated without exercising a therapeutic effect. The present study aimed to prepare three lipoprotein formulations (HDL-, LDL-, and VLDL-based) loaded with cyclosporin A for the treatment of colitis in a murine model. After an intravenous injection of a drug dose of 2 mg/kg, clinical activity (colon weight/length ratio) and therapeutic effects (evaluated by the inflammatory markers MPO and TNF-α) were compared with those of the untreated colitis control group. All CycloA-containing lipoproteins reduced clinical activity, with a significant decrease in the case of LDL-CycloA formulation, which also led to the higher therapeutic effect.

Tackling the various classes of nano-therapeutics employed in topical therapy of psoriasis.

Psoriasis is a dermatological chronic skin condition with underlying autoimmune etiology. It deeply affects patients' quality of life. Therefore, it was an interesting target for researchers throughout the past years. Conventionally, the treatment options include anti-inflammatory agents, immune suppressants, biologic treatment, and phototherapy. Nanotechnology offers promising characteristics that allow for tailoring a drug carrier to achieve dermal targeting, improved efficacy and minimize undesirable effects. Being the safest route, the first line of treatment and a targeted approach, we solely discussed the use of the topical route, combined with advanced drug delivery systems for the management of psoriasis in this article. Advanced systems include polymeric, metallic, lipidic and hybrid nanocarriers incorporating different active agents. All formerly mentioned types of drug delivery systems were investigated through the past decades for the purpose of topical application on psoriatic plaques. Scientists' efforts are promising to reach an optimized formula with a convenient dosage form to improve efficacy, safety, and compliance for the treatment of psoriasis. Accordingly, it will offer a better quality of life for patients.

Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs.

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-co-glycolic acid) (PLGA) NPs (155 ±â€¯10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 °C) or in normothermia (37 °C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.

A nanoparticle-based approach to improve the outcome of cancer active immunotherapy with lipopolysaccharides.

This study sought to develop a simple nanoparticle-based approach to enhance the efficiency and tolerability of lipopolysaccharide (LPS), a potent ligand of Toll-like Receptor 4 (TLR4), for immunotherapy in cancer. Despite holding promise within this context, the strong pro-inflammatory properties of LPS also account for its low tolerability given localized and systemic side effects, which restrict the administrable dosage. Herein, we investigated the effect of LPS decoration as a surface-active molecule on a polymeric matrix upon its efficiency and tolerability. The LPS-decorated nanoparticles (LPS-NP) were about 150 nm in size, with slightly negative zeta potential (about -15 mV) and acceptable LPS incorporation (about 70%). In vitro, the particles accounted for a higher induction of apoptosis in tumor cells cultured with murine splenocytes compared to LPS solution. When used for the treatment of a murine syngeneic colorectal tumor model, higher intratumoral deposition of the particle-bound LPS was observed. Furthermore, unlike LPS solution, which accounted for localized necrosis at high concentrations, treatment of tumor-bearing animals with equivalent doses of LPS-NP was well tolerated. We propose that the observed localized necrosis can be Shwartzman phenomenon, which, due to modulated 24-h post-injection systemic TNF-α and LPS concentrations, have been avoided in case of LPS-NP. This has in turn enhanced the therapeutic efficiency and enabled complete tumor regression at concentrations at which LPS solution was intolerable. The findings indicate that nanoparticles can serve as beyond carriers for the delivery of superficially decorated LPS molecules, but impact their overall efficiency and tolerability in cancer therapy.

Buccal delivery of low molecular weight heparin by cationic polymethacrylate nanoparticles.

Buccal delivery seems to be a very promising administration route for macromolecular drugs. Here, we explored the potential of cationic polymethacrylate nanoparticles (NPs) as a carrier system for the buccal delivery of low molecular weight heparin (LMWH). LMWH-loaded NPs were prepared by emulsification solvent diffusion method and the NPs were analyzed for their physiochemical properties, rheological evaluations and ex vivo transport studies across buccal mucosa. The prepared LMWH-loaded NPs showed a mean diameter between 400 and 500nm with unimodal size distribution with negative surface charge. Viscosity measurements revealed a positive rheological synergism between the prepared NPs and mucin when mixed under physiological conditions. After 4h, about 6.3±0.9% of LMWH was released in case of using Eudragit® RS (ERS); while Eudragit® RL (ERL) NPs released only 3.0±0.3 % of its LMWH content and this incomplete release was slightly ameliorated in the presence of mucin reaching to 7.2±0.3 % and 4.8±0.3 % for ERS and ERL, respectively. The ex-vivo permeability of heparin through the buccal mucosa was significantly increased after using polymetharylate NPs while no heparin permeation was detected from free heparin solution. Confocal laser scanning microscopy (CLSM) imaging indicated the mucoadhesive properties of the polymetharylate NPs where the drug-free NPs were detected in the superficial layers of buccal mucosa. LMWH-loaded NPs had less mucoadhesive properties showing significant deeper penetration of the mucosa. The results indicated that mucoadhesive cationic polymethacrylate NPs offer a possible approach for the buccal delivery of heparin.

In vivo skin penetration of macromolecules in irritant contact dermatitis.

Recently, a selective preferential accumulation of polymeric nanoparticles (in the size range around 100nm) has been observed in the follicular system of dermatitis skin. The present investigation aimed at clearly investigating the effect of irritant contact dermatitis on the barrier permeability for colloidal systems below this size range, namely quantum dots and hydrophilic macromolecules. Irritant dermatitis was induced in mice and the penetrability of quantum dots (5nm) and hydrophilic dextran molecules has been tracked in both healthy and inflamed skin using confocal laser scanning microscopy. The selective accumulation of the quantum dots was clearly observed in inflamed skin while hydrophilic dextran behaved similarly in both healthy and inflamed skin. The therapeutic potential for the transdermal delivery of peptide drugs through inflamed skin has been also tested in rats. Results revealed that the transdermal permeation of insulin and calcitonin was not significantly enhanced in dermatitis compared to healthy skin. On the other side, permeation through stripped skin was significantly higher. However, the effect was limited and shorter compared to the SC injection where tmin was 0.5h and 2h with a 70% and 46% reduction in blood glucose levels for the stripped skin and the SC injection respectively. Similarly, tmin was 4h and 8h with area under the curve of 161±65% and 350±97% for the stripped skin and the SC injection respectively. In conclusion, the changes in skin permeability accompanied with skin inflammation did not affect its permeability to peptide drugs. Our findings also underline that experiments with the tape stripped skin model as a surrogate for inflamed skin can risk misleading conclusions due to significant difference of skin permeability between the tape stripped skin and inflamed skin.

Stability of fluorescent labels in PLGA polymeric nanoparticles: Quantum dots versus organic dyes.

Polymeric nanoparticles (NPs) are currently being investigated for various therapeutic, diagnostic and drug delivery applications. The study of their interactions and fate in biological systems is frequently performed via their fluorescent labeling and following them using fluorescent microscopy. Quantum dots are proposed as stable fluorescent label and compared to other organic dyes (Nile red and DiI) in terms of their entrapment, diffusion in different aqueous or lipophilic media and photostability. In vitro transfer to hydrophilic PBS solution showed that after 8h, 4.2±2.2, 15.5±2.0 and 0.9±0.02% was released from the QDs, NR and DiI nanoparticles, respectively. However, higher diffusion rates were observed in the lipophilic medium chain triglyceride and artificial sebum for all the dyes used. Fluorescent intensity of the three different markers was found to be stable over a period of 24h. Continuous illumination with laser beam using a confocal laser scanning microscopy indicated the superior stability of quantum dots compared to the other organic dyes. Skin permeation experiments have shown that QDs were the most representative marker for the polymeric nanoparticles skin penetration.

Finite and infinite dosing: difficulties in measurements, evaluations and predictions.

Due to the increased demand for reliable data regarding penetration into and permeation across human skin, assessment of the absorption of xenobiotics has been gaining in importance steadily. In vitro experiments allow for determining these data faster and more easily than in vivo experiments. However, the experiments described in literature and the subsequent evaluation procedures differ considerably. Here we will give an overview on typical finite and infinite dose experiments performed in fundamental research and on the evaluation of the data. We will point out possible difficulties that may arise and give a short overview on attempts at predicting skin absorption in vitro and in vivo.