Non-invasive caffeinated-nanovesicles as adipocytes-targeted therapy for cellulite and localized fats.

Caffeine (CAF) is a non-selective adenosine A1 receptor antagonist which predominates in fat cells. When CAF binds to adenosine receptors, it increases cyclic adenosine monophosphate; inhibiting adipogenesis and inducing fat lipolysis. Resveratrol (RSV) is an antioxidant polyphenol possessing different anti-obesity mechanisms. Topical application of both hydrophilic CAF and lipophilic RSV is limited. This study aimed to develop novel caffeinated-resveratrol bilosomes (CRB) and caffeine-bilosomes (CB) that could non-invasively target and deposit in fat cells. RSV bilosomes (RB) were prepared as a non-targeted system for comparison. CRB showed nanosize (364.1 nm ±6.5 nm) and high entrapment for both active compounds. Rats treated topically with CRB revealed a significant decrease (P = 0.039) in body weight. Histological analysis of the excised skin demonstrated a reduction in the subcutaneous fatty layer thickness and a decrease in the size of connective tissue-imbedded fat cells. Kidney histological examination of RB-treated rats showed subcapsular tubular epithelial cells with cytoplasmic vacuolation. This reflects a systemic effect of RSV from the non-targeted RB compared to CRB, which had a targeting effect on the adipose tissue. In conclusion, CAF in CRB significantly enhanced RSV deposition in adipose tissue and assisted its local-acting effect for managing obesity and cellulite.

Rhein methotrexate-decorated solid lipid nanoparticles altering adjuvant arthritis progression through endoplasmic reticulum stress-mediated apoptosis.

Methotrexate (MTX) and diacerein (DIA) are two of the most potent disease-modifying anti-rheumatic drugs used for the treatment of rheumatoid arthritis (RA). DIA has reflected some GIT and hepatobiliary manifestations in numerous cases. It undergoes biotransformation in the liver into the active metabolite rhein (RH) which is characterized by its excellent anti-inflammatory activity and lower side effects. However, RH's hydrophobic nature and low bioavailability do not encourage its use in RA. The current study aims to use RH in combination with MTX in targeted solid lipid nanoparticles (RH-MTX-SLNs) for better effectiveness and shadowing light on its possible mechanistic pathways. RH-MTX-SLNs were prepared and assessed for their quality attributes. The effect of the formulation was assessed in-vivo in an adjuvant arthritis animal model investigating the role of the endoplasmic reticulum stress (ERS)-induced apoptosis. Results revealed that RH-MTX-SLNs were in the suitable nanosized range with high negative zeta potential indicating good stability. In-vivo, RH-MTX-SLNs significantly improved all measured inflammatory and arthritic markers, confirmed by electron microscopy and histology examination of the joints. Besides, the formulation was able to alter the ERS-mediated apoptosis. In conclusion, RH-MTX-SLNs can represent a promising therapeutic approach for RA showing significant anti-arthritic activity.

Fucoidan/hyaluronic acid cross-linked zein nanoparticles loaded with fisetin as a novel targeted nanotherapy for oral cancer.

Fisetin (FS) is an anticancer drug having potential role in oral tumors management. However, its clinical application is limited due to its hydrophobicity and instability. Bioactive polymers-based nanosystems have a great potential in cancer therapy. Herein, different biopolymers were selected for their anticancer activity and targeting ability for nanoparticles preparation namely; fucoidan (FU), zein (Zn) and hyaluronic acid (HA). The selected FS-loaded cross-linked Zn nanoparticles (ZFH) which contains HA& FU for Zn nanoparticles stabilization showed the most suitable particle size (196 ± 6.53 nm), mean surface net charge (-38.8 ± 1.47 mV) and entrapment efficiency (98 ± 1.2 %). This is the first study to utilize both HA &FU not only for stabilization but also for dual targeting effect due to their targeting ability to multiple tumor targets. In-vitro anticancer activity of ZHF revealed remarkable uptake by SCC-4 cells with significant cytotoxic action. Further, ZHF was appraised using 4-nitroquinoline 1-oxide (4-NQO)-induced oral cancer in-vivo; ZHF significantly reduced OSCC-specific serum biomarkers levels, histologic tumor grade and increased caspase-3 level. Moreover, potential of destroying two key tumor regulatory cells; TECs and CSCs, was evaluated using their specific markers. The elaborated ZFH nanoparticles could be considered as promising targeted nanotherapy for oral cancer treatment with enhanced efficacy and survival rate.

Novel mucoadhesive celecoxib-loaded cubosomal sponges: Anticancer potential and regulation of myeloid-derived suppressor cells in oral squamous cell carcinoma.

Oral squamous-cell carcinoma (OSCC) is a widespread health problem. Myeloid-derived suppressor cells (MDSCs) are major tumor microenvironment (TME) population that govern many carcinogenesis aspects by establishing immunosuppressive milieu favoring tumor aggressiveness and treatment resistance. Cyclooxygenase-2 (COX-2) regulates MDSCs activity, hence, COX-2-selective inhibition by celecoxib (CXB) showed good anticancer effect at relatively high doses with possible subsequent cardiovascular complications. Therefore, targeted CXB delivery to MDSCs may represent a promising OSCC treatment strategy. Novel mucoadhesive-cubosomal buccal sponges were prepared for MDSCs targeting and were evaluated for their in-vitro quality attributes, ex-vivo mucoadhesion using buccal chicken-mucosa. Optimally-selected formulation showed considerable uptake by CD33+/11b+MDSCs in human OSCC cell-line (SCC-4) when quantitatively analyzed by flow-cytometry and examined using confocal-laser microscope. Optimum formulations loaded with low CXB doses (12 mg) were promoted to in-vivo studies via local application, using 4-nitroquinoline-1-oxide-induced OSCC in rats, and compared to their corresponding CXB gels. SP16 revealed the highest ability to decrease MDSC activation, recruitment and TME-immunosuppression in the isolated tumors. Consequently, SP16 exerted the greatest capacity to reduce histologic tumor grade, the OSCC-specific serum tumor markers levels, cancer hallmarks and stemness markers. CXB-loaded cubosomal sponges preferentially target MDSCs with noticeable anticancer potential and may exemplify novel mucoadhesive nanocarriers for OSCC treatment.

Surface modified genistein phytosome for breast cancer treatment: In-vitro appraisal, pharmacokinetics, and in-vivo antitumor efficacy.

Based on phytosomes advantages over liposomes, hyaluronic acid (HA) with/out pegylated phospholipid was used to develop surface-modified genistein (Gen) phytosome as Gen pegylated hyaluophytosomes (G-PHA) and Gen hyaluophytosomes (G-HA) as novel delivery systems for breast cancer treatment. In this study, in-vitro characterization of G-HA and G-PHA shows PS 144.2 ±1.266 nm and 220.3 ±2.51 nm, ZP -30.9 ±0.75 and -32.06 ±0.305 respectively. Morphological elucidation shows HA covers the surface of G-HA and the presence of a transparent layer of PEG surrounding G-PHA. In-vitro release shows a significant slow Gen release from G-HA, and G-PHA compared to Gen solution and Gen phytosomes. In-vivo bioavailability data shows improvement in bioavailability for G-HA and G-PHA compared to Gen suspension (AUC0-t: 3.563 ± 0.067, 2.092 ± 0.058, 0.374 ± 0.085 µg/ml*h respectively). Therapeutic evaluation of the prepared targeted formulations was carried out by subcutaneous injection in an EAC-induced breast cancer model in mice. G-HA and G-PHA show a promising chemotherapeutic effect in terms of lowering the tumor size and tumor biomarkers (CEA: -34.6, -44.7 & CA15.3: -77.8, -81.6, respectively). This reduction in their values compared to Gen phytosomes, Gen suspension, and the control group is attributed to high Gen accumulation at the target organ owing to targeting properties of HA that are used in phytosomal surface modification in G-HA. Additionally, the presence of MPEG2000-DSPE in G-PHA tends to improve interstitium lymphatic drainage following SC administration, resulting in maximizing the therapeutic benefits of breast cancer despite the difference in pharmacokinetics behavior compared to G-HA. These formulations can be further studied for metastatic breast cancer.

Oral genistein-loaded phytosomes with enhanced hepatic uptake, residence and improved therapeutic efficacy against hepatocellular carcinoma.

Genistein (Gen) is one of the most potent soy isoflavones used for hepatocellular carcinoma (HCC) treatment. Low aqueous solubility and first-pass metabolism are the main obstacles resulting in low Gen oral bioavailability. The current study aims to introduce phytosomes as an approach to improve Gen solubility, protect it from metabolism by complexation with phospholipids (PL), and get used to PL in Gen lymphatic delivery. Different forms of PL namely: Lipiod® S100, Phosal® 53 MCT, and Phosal®75 SA were used in phytosomes preparation GP, GPM, and GPL respectively. The effect of formulation components on Gen absorption, metabolism, and liver accumulation was evaluated following oral administration to rats. Cytotoxicity and cellular uptake studies were applied on HepG2 cells and in-vivo anti-tumor studies were applied to the DEN-mice model. Results revealed that GP and GPL remarkably accumulated Gen aglycone in hepatic cells and minimized the metabolic effect on Gen. They significantly increased the intracellular accumulation of Gen in its complex form in HepG2 cells. Their cytotoxicity is time-dependent according to the complex stability. The enhanced in-vivo anti-tumor effect was observed for GP and GPL compared to Gen suspension on DEN-induced HCC in mice. In conclusion, Gen-phytosomes can represent a promising approach for liver cancer treatment.

Smart Ultrasound-Triggered Doxorubicin-Loaded Nanoliposomes With Improved Therapeutic Response: A Comparative Study.

Doxorubicin (DOX) effectiveness in cancer treatment is hampered by its nonspecific accumulation in organs. Ultrasound (US) is a promising noninvasive targeting approach. Currently, studies focus on developing more DOX-loaded US-triggered formulations with different composition, DOX doses, and US intensities. No studies were emerged to compare and select the most effective approach to endure. The aim of this study is to prepare and comparatively address the therapeutic potential of 2 different US-tunable nanosized liposomes while minimizing DOX dose and US intensity. One of the liposomes is tailored to be responsive for US non-thermal effects (DOX-USLs) and the other is designed to be thermoresponsive (DOX-TSLs). Both systems were compared in terms of cellular uptake, cell viability and apoptosis using HeLa cells as a cancer model. The IC50 of DOX-USLs and DOX-TSLs was 2.5-5 times lower than that of free DOX. IC50 reflected the significant superior cytotoxicity of DOX-TSLs (0.1 µg/mL) over DOX-USLs (0.2 µg/mL). Cellular uptake indicated that DOX-TSLs were inside the nucleus while DOX-USLs were accumulated everywhere in the intracellular space with lower fluorescent intensity inside the nucleus. However, both showed enhanced apoptosis in terms of enhanced caspase-3 activity, reduced glutathione levels and DNA fragmentation when compared to free DOX treatment.

Oral vitamin-A-coupled valsartan nanomedicine: High hepatic stellate cell receptors accessibility and prolonged enterohepatic residence.

So far, liver fibrosis still has no clinically-approved treatment. The loss of stored vitamin-A (VA) in hepatic stellate cells (HSCs), the main regulators to hepatic fibrosis, can be applied as a mechanism for their targeting. Valsartan is a good candidate for this approach; it is a marketed oral-therapy with inverse- and partial-agonistic activity to the over-expressed angiotensin-II type1 receptor (AT1R) and depleted nuclear peroxisome proliferator-activated receptor-gamma (PPAR-γ), respectively, in activated HSCs. However, efficacy on AT1R and PPAR-γ necessitates high drug permeability which is lacking in valsartan. In the current study, liposomes were used as nanocarriers for valsartan to improve its permeability and hence efficacy. They were coupled to VA and characterized for HSCs-targeting. Tracing of orally-administered fluorescently-labeled VA-coupled liposomes in normal rats and their fluorescence intensity quantification in different organs convincingly demonstrated their intestinal entrapment. On the other hands, their administration to rats with induced fibrosis revealed preferential hepatic, and less intestinal, accumulation which lasted up to six days. This indicated their uptake by intestinal stellate cells that acted as a depot for their release over time. Confocal microscopical examination of immunofluorescently-stained HSCs in liver sections, with considerable formula accumulation, confirmed HSCs-targeting and nuclear uptake. Consequently, VA-coupled valsartan-loaded liposomes (VLC)-therapy resulted in profound re-expression of hepatic Mas-receptor and PPAR-γ, potent reduction of fibrogenic mediators' level and nearly normal liver function tests. Therefore, VLC epitomizes a promising antifibrotic therapy with exceptional extended action and additional PPAR-γ agonistic activity.

Gel in core carbosomes as novel ophthalmic vehicles with enhanced corneal permeation and residence.

Carbopol is a good bio-adhesive polymer that increases the residence time in the eye. However, the effect of blinking and lacrimation still reduce the amount of polymer and the incorporated drug available for bioadhesion. Gel-core liposomes are advanced systems offering benefits making it a good tool for improved ocular drug delivery and residence time. Incorporation of carbopol in gel-core liposomes and their potential in ocular delivery have not so far been investigated. Fluconazole (FLZ) was selected as a challenging important ocular antifungal suffering from poor corneal permeation and short residence time. In this study, gel-core carbosomes have been elaborated as novel carbopol-based ophthalmic vehicles to solve ocular delivery obstacles of FLZ and to sustain its effect. Full in vitro appraisal was performed considering gel-core structure, entrapment efficiency, particle size and stability of the vesicles as quality attributes. Structure elucidation of the nanocarrier was performed using optical, polarizing and transmission electron microscopy before and after Triton-X100 addition. Ex-vivo ocular permeation and in vivo performance were investigated on male albino rabbits. Optimized formulation (CBS5) showed gel-core structure, nanosize (339.00 ±â€¯5.50 nm) and not defined before (62.00% ±â€¯1.73) entrapment efficiency. Cumulative amount of CBS5 permeated ex-vivo after 6 h, was 2.43 and 3.43 folds higher than that of conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of CBS5 showed significantly higher AUC0-24 h (487.12 ±â€¯74.80) compared to that of FLZ suspension (204.34 ±â€¯7.46) with longer residence time in the eye lasts for more than 18 h. In conclusion, novel gel-core carbosomes could successfully be used as a promising delivery system for chronic ocular diseases.

Bioadhesive Chitosan-Coated Cationic Nanoliposomes With Improved Insulin Encapsulation and Prolonged Oral Hypoglycemic Effect in Diabetic Mice.

Oral administration of insulin is hampered by the lack of carriers that can efficiently achieve high encapsulation, avoid gastric degradation, overcome mucosal barriers, and prolong the hypoglycemic effect. Chitosan (CS)-coated insulin-loaded cationic liposomes have been developed and optimized for improved oral delivery. Liposomes were prepared cationic to improve insulin encapsulation. CS was selected as a mucoadhesive coat to prolong the system's residence and absorption. The performance of CS-coated liposomes compared with uncoated liposomes was examined in vitro, ex vivo, and in vivo in streptozotocin-induced diabetic mice. Free uncoated liposomes showed high positive zeta potential of +58.8 ± 2.2 mV that reduced (+29.9 ± 1.4 mV) after insulin encapsulation, confirming the obtained high entrapment efficiency of 87.5 ± 0.6%. CS-coated liposomes showed nanosize of 439.0 ± 12.3 nm and zeta potential of +60.5 ± 1.9 mV. In vitro insulin release was limited to 18.9 ± 0.35% in simulated gastric fluid, whereas in simulated intestinal fluid, 73.33 ± 0.68% was released after 48 h from CS-coated liposomes. Ex vivo intestinal mucoadhesion showed increased tissue residence of CS-coated liposomes compared with uncoated liposomes. A striking reduction in the glucose level was observed 1 h after oral administration of CS-coated liposomes and maintained up to 8 h (p <0.01 vs. insulin solution or uncoated liposomes) within the normal value 129.29 ± 3.15 mg/dL. In conclusion, CS-coated insulin-loaded cationic liposomes improved loading efficiency with promising prolonged pharmacological effect.

Hyalugel-integrated liposomes as a novel ocular nanosized delivery system of fluconazole with promising prolonged effect.

Fungal infections need long-term therapy with the proper antifungal agent. Despite effectiveness, Fluconazole (FLZ) ocular delivery is constrained by limited penetration, short residence time, in addition to the common barriers of the eye. Hyalugel-integrated liposomes were designed as novel ocular delivery systems integrating hyaluronic acid (HA) inside and surrounding vesicles by a simple preparation technique. The impact of combining HA hydrogel and liposomes was investigated in a series of different formulations. Full in-vitro optimization was performed regarding; HA and FLZ concentration, entrapment efficiency, particle size and stability to select the formula with the best characteristics. Structure elucidation of gel integration was done using polarizing and transmission electron microscopes before and after Triton-X100 addition. Corneal deposition and permeation were examined ex-vivo and in-vivo on male albino rabbits. Selected formulation (HYS7) showed gel-integrated structure, nanosize (218.50±4.50nm) and % EE 42.81%±1.66. Ex-vivo cumulative corneal permeation of FLZ after 6h from HYS7, was 2.99 and 4.18 folds higher than conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of HYS7 showed unprecedented sustained effect of FLZ reaching 24h. In conclusion, novel hyalugel-integrated liposomes significantly enhanced corneal permeability compared to conventional liposomes and FLZ suspension. They would be promising alternates for eye drops; decreasing frequency of administration and increasing patients' compliance.

Hepatic stellate cell-targeted imatinib nanomedicine versus conventional imatinib: A novel strategy with potent efficacy in experimental liver fibrosis.

Liver fibrosis is a global health problem without approved treatment. Imatinib inhibits two key profibrotic pathways; platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-ß) and thus can be used to treat liver fibrosis. However, conventional imatinib therapy is hampered by low concentration at target tissue and increased toxicity to other tissues especially heart, lung and liver. Since hepatic stellate cells (HSCs) are the main contributors to liver fibrosis pathogenesis and sole hepatic vitamin A (VA) storage cells, they can be actively targeted by coupling liposomes to VA. In this study, novel VA-coupled imatinib-loaded liposomes (ILC) were prepared and optimized regarding VA-coupling efficiency, imatinib entrapment efficiency, and particle size. Preferential accumulation of the selected formula in liver was proved by tracing intraperitoneally (i.p.)-injected VA-coupled liposomes loaded with Nile Red (LCNR) to rats with CCl4-induced liver fibrosis using live animal imaging. Co-localization of LCNR with immunofluorescently-labeled PDGFR-ß in frozen liver tissue sections confirmed HSCs targeting. ILC bio-distribution, following single i.p. injection, revealed 13.5 folds higher hepatic accumulation than conventional imatinib in addition to limited bio-distribution to other organs including heart and lung reflecting diminished adverse effects. ILC therapy resulted in a potent inhibition of phosphorylated PDGFR-ß expression when compared to conventional imatinib. Subsequently, there was a statistically significant improvement in liver function tests and reversal of hepatotoxicity along with liver fibrosis. Anti-fibrotic effect was evident from histopathologic Ishak score reduction as well as normalization of the level of profibrotic mediators (hydroxyproline, TGF-B and matrix metalloproteinase-2). Thus, HSC-targeted imatinib therapy shows outstanding anti-fibrotic effects with reduced cytotoxicity compared to conventional imatinib. It can represent a promising novel approach for liver fibrosis treatment.

Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges.

Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.

Novel curcumin-loaded gel-core hyaluosomes with promising burn-wound healing potential: Development, in-vitro appraisal and in-vivo studies.

Despite its effectiveness, curcumin (Curc) dermal delivery is handicapped by hydrophobicity, high metabolism and poor skin permeation. In this work, the potential of novel self-assembled nanogels, namely gel-core hyaluosome (GC-HS) to enhance Curc delivery to wound sites, enhance healing rate and decrease scar formation was evaluated. Curc-GC-HS were prepared using film hydration technique and evaluated regarding size, zeta potential (ZP), entrapment efficiency (% EE), and in vitro release. Structure elucidation was performed using light, polarizing and transmission electron microscopy (TEM). In-vivo burn-wound healing potential, skin deposition ability and histological study were evaluated using female Sprague Dawley rats. Curc-GC-HS were compared to conventional transfersomal gel (Curc-T-Pl gel), and other conventional gels. Curc-GC-HS showed nanosize (202.7 ± 0.66 nm), negative ZP (-33 ± 2.6 mV) and % EE (96.44 ± 1.29%). TEM revealed discrete vesicles with characteristic bilayer structure. Polarizing microscopy proposed liquid crystalline consistency. Burn-wound healing study showed that Curc-GC-HS was the only system exhibiting marked improvement at day 7 of treatment. At 11th day, Curc-GC-HS treated wounds showed almost normal skin with no scar confirmed by histological analysis. Curc-GC-HS showed five folds higher skin deposition compared to conventional Curc-T-Pl gel. To conclude, novel gel-core hyaluosomes elaborated are promising nanogels able to increase Curc skin penetration and dermal localization while protecting it against degradation. Future perspective encompasses assessing potential of novel nanocarrier for skin cancer therapy.

Novel Self-assembled, Gel-core Hyaluosomes for Non-invasive Management of Osteoarthritis: In-vitro Optimization, Ex-vivo and In-vivo Permeation.

PURPOSE: Hyaluronic acid (HA) is an imperative biomaterial with desirable rheological properties to alleviate symptoms of osteoarthritis. Nevertheless, scantly percutaeous permeation of this macromolecule handicaps its effective use for orthopedics and triggers intra-articular injection as the only surrogate. This study presents novel self-assembeld HA-based gel core elastic nanovesicles, (hyaluosomes; GC-HS), for non-invasive transdermal delivery of HA. METHODS: GC-HS were prepared with 1% HA using simple film hydration technique. Their size, zeta potential, percentage entrapment efficiency (% EE), elasticity, and ex-vivo transdermal permeation were evaluated compared to conventional liposomes CL. Structure elucidation of the formed novel system was performed using light, polarizing and transmission electron microscopy. In-vivo permeation of GC-HS through knee joints of female Sprague Dawley rats was compared to CL and HA alone. RESULTS: GC-HS showed nanosize (232.8 ± 7.2), high negative zeta potential (-45.1 ± 8.3) and higher elasticity (size alteration 5.43%) compared to CL. This novel system has self-penetration enhancing properties compared to CL and plain gel. GC-HS showed self-assembled properties and high physically stable for at least 6 months at 4°C. Ex-vivo permeation of HS was significantly higher than CL and plain HA gel alone. In-vivo study exhibited significant six folds increase in transdermal permeation of HA to knee joints from GC-HS compared to plain HA gel. CONCLUSION: Novel GC-HS are promising nanogels for topical management of osteoarthritis surrogating the need for intra-articular injection.

Lecithin-based nanostructured gels for skin delivery: an update on state of art and recent applications.

Conventional carriers for skin delivery encounter obstacles of drug leakage, scanty permeation and low entrapment efficiency. Phospholipid nanogels have recently been recognized as prominent delivery systems to circumvent such obstacles and impart easier application. The current review provides an overview on different types of lecithin nanostructured gels, with particular emphasis on liposomal versus microemulsion gelled systems. Liposomal gels investigated encompassed classic liposomal hydrogel, modified liposomal gels (e.g. Transferosomal, Ethosomal, Pro-liposomal and Phytosomal gels), Microgel in liposomes (M-i-L) and Vesicular phospholipid gel (VPG). Microemulsion gelled systems encompassed Lecithin microemulsion-based organogels (LMBGs), Pluronic lecithin organogels (PLOs) and Lecithin-stabilized microemulsion-based hydrogels. All systems were reviewed regarding matrix composition, state of art, characterization and updated applications. Different classes of lecithin nanogels exhibited crucial impact on transdermal delivery regarding drug permeation, drug loading and stability aspects. Future perspectives of this theme issue are discussed based on current laboratory studies.