Nanocarriers significantly augment the absorption of ocular-delivered drugs: A comparative meta-analysis study.

This study presents a meta-analysis that compiles information collected from several studies aiming to prove, by evidence, that nanocarriers out-perform conventional formulations in augmenting the bioavailability of ocular topically administered drugs. Data was further categorized into two subgroups; polymeric-based nanocarriers versus their lipid-based counterparts, as well as, naturally-driven carriers versus synthetically-fabricated ones. After normalization, the pharmacokinetic factor, area under the curve (AUC), was denoted as the "effect" in the conducted study, and the corresponding Forest plots were obtained. Our meta-analysis study confirmed the absorption enhancement effect of loading drugs into nanocarriers as compared to conventional topical ocular dosage forms. Interestingly, no significant differences were recorded between the polymeric and lipidic nanocarriers included in the study, while naturally-driven nanoplatforms were proven superior to the synthetic alternatives.

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 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.

Insightful exploring of advanced nanocarriers for the topical/transdermal treatment of skin diseases.

Dermatological products constitute a big segment of the pharmaceutical market. From conventional products to more advanced ones, a wide variety of dosage forms have been developed till current date. A representative of the advanced delivery means is carrier-based systems, which can load large number of drugs for treatment of dermatological diseases, or simply for cosmeceutical purposes. To make them more favorable for topical delivery, further incorporation of these carriers in a topical vehicle, such as gels or creams is made. Therefore in this review article, an overview is compiled of the most commonly encountered novel carrier based topical delivery systems; namely lipid based (nanoemulsions, microemulsions, solid lipid nanoparticles [SLNs] and nanostructured lipid carriers [NLCs]), and vesicular carriers (non-deformable, such as liposomes, niosomes, emulsomes and cerosomes, and deformable, such as transfersomes, ethosomes, transethosomes, and penetration enhancer vesicles), with special emphasis on those loaded in a secondary gel vehicle. A special focus was made on the commonly encountered dermatological diseases, such as bacterial and fungal infections, psoriasis, dermatitis, eczema, vitiligo, oxidative damage, aging, alopecia, and skin cancer.

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.

Coenzyme Q10 phospholipidic vesicular formulations for treatment of androgenic alopecia: ex vivo permeation and clinical appraisal.

INTRODUCTION: Coenzyme Q10 (CoQ10) is an antioxidant molecule with anti-aging activity on human hair, and because of its pharmaceutical limitations such as large molecular weight, high lipophilicity and poor water solubility, its therapeutic effectiveness has been hampered. Therefore, different vesicular nanocarriers were developed in the current work, for enhancement of the skin penetration of CoQ10 for treatment of androgenic alopecia. AREAS COVERED: In order to overcome the poor skin penetration of CoQ10, it was formulated in liposomes, transfersomes, ethosomes, cerosomes and transethosomes using the thin-film hydration method. Results revealed that transethosomes were the carrier of choice for CoQ10, in which it displayed a particle size of 146 nm, zeta potential -55 mV and entrapment efficiency of 97.63%. Transethosomes also achieved the highest deposition percentage for CoQ10, exceeding 95% in the different skin layers. Upon clinical examination in patients suffering from androgenic alopecia, CoQ10 transethosomes displayed better clinical response than the administration of CoQ10 solution, which was further confirmed by dermoscopic examination. EXPERT OPINION: Findings of this study further prove that loading antioxidants such as CoQ10 in nanocarriers maximizes their therapeutic efficiency, and opens many opportunities for their application in treatment of several other topical diseases.

Chrysin nanocapsules with dual anti-glycemic and anti-hyperlipidemic effects: Chemometric optimization, physicochemical characterization and pharmacodynamic assessment.

Chrysin is a flavonoid with various biological and therapeutic properties. However, its poor oral bioavailability and solubility are challenging barriers against its therapeutic use, which can be circumvented via encapsulation in a suitable nanocarrier. Therefore, the aim of this work was to prepare polymeric chrysin nanocapsules based on polylactic-glycolic acid PLGA with improved oral therapeutic potential, by optimization of their physicochemical properties using response surface methodology. Diabetes was induced in an animal model using streptozotocin to assess the anti-hyperglycemic activity of the selected formulation, and hyperlipidemia was induced in another animal model using a high fat diet to assess its anti-hyperlipidemic activity. Results revealed that the selected chrysin nanocapsular formulation exhibited particle size of 176 ± 2.10 nm, polydispersity index of 0.22 ± 0.01, negative zeta potential, drug entrapment efficiency of 87.10% ± 6.71, a controlled release of chrysin over a period of 24 h, and a significant physical stability after storage for 3 months. Compared to chrysin suspension, the selected nanocapsular formulation exhibited marked anti-hyperglycemic effect for up to 24 h, as well as superior anti-hyperlipidemic potential for 28 days. These improvements in chrysin therapeutic action after its encapsulation into polymeric nanocapsules delineate it as a promising remedy for oral treatment of diabetes and hyperlipidemia.

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.

A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route.

The use of nanocarrier delivery systems for direct nose to brain drug delivery shows promise for achieving increased brain drug levels as compared to simple solution systems. An example of such nanocarriers is emulsomes formed from lipid cores surrounded and stabilised by a corona of phospholipids (PC) and a coating of Tween 80, which combines the properties of both liposomes and emulsions. Oxcarbazepine (OX), an antiepileptic drug, was entrapped in emulsomes and then localized in a poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer thermogel. The incorporation of OX emulsomes in thermogels retarded drug release and increased its residence time (MRT) in rats. The OX-emulsome and the OX-emulsome-thermogel formulations showed in vitro sustained drug release of 81.1 and 53.5%, respectively, over a period of 24 h. The pharmacokinetic studies in rats showed transport of OX to the systemic circulation after nasal administration with a higher uptake in the brain tissue in case of OX-emulsomes and highest MRT for OX-emulsomal-thermogels as compared to the IN OX-emulsomes, OX-solution and Trileptal® suspension. Histopathological examination of nasal tissues showed a mild vascular congestion and moderate inflammatory changes around congested vessels compared to saline control, but lower toxic effect than that reported in case of the drug solution.

Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies.

Lipid-based nanovectors offer effective carriers for brain delivery by improving drug potency and reducing off-target effects. Emulsomes are nano-triglyceride (TG) carriers formed of lipid cores supported by at least one phospholipid (PC) sheath. Due to their surface active properties, PC forms bilayers at the aqueous interface, thereby enabling encapsulated drug to benefit from better bioavailability and stability. Emulsomes of oxcarbazepine (OX) were prepared, aimed to offer nanocarriers for nasal delivery for brain targeting. Different TG cores (Compritol(®), tripalmitin, tristearin and triolein) and soya phosphatidylcholine in different amounts and ratios were used for emulsomal preparation. Particles were modulated to generate nanocarriers with suitable size, charge, encapsulation efficiency and prolonged release. Cytotoxicity and pharmacokinetic studies were also implemented. Nano-spherical OX-emulsomes with maximal encapsulation of 96.75% were generated. Stability studies showed changes within 30.6% and 11.2% in the size and EE% after 3 months. MTT assay proved a decrease in drug toxicity by its encapsulation in emulsomes. Incorporation of OX into emulsomes resulted in stable nanoformulations. Tailoring emulsomes properties by modulating the surface charge and particle size produced a stable system for the lipophilic drug with a prolonged release profile and mean residence time and proved direct nose-to-brain transport in rats.

Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery.

Transfersomes are highly efficient edge activator (EA)-based ultraflexible vesicles capable of, non-invasively, trespassing skin by virtue of their high, self-optimizing deformability. This investigation presents different approaches for the optimization of Transfersomes for enhanced transepidermal delivery of Diclofenac sodium (DS). Different methods of preparation, drug and lipid concentrations and vesicle compositions were employed, resulting in ultraflexible vesicles with diverse membrane characteristics. Evaluation of Transfersomes was implemented in terms of their shapes, sizes, entrapment efficiencies (EE%), relative deformabilities and in vitro skin permeation. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% (Span 85>Span 80>Na cholate>Na deoxycholate>Tween 80). Whereas, those prepared using 85:15% (w/w) ratio showed highest deformability (Tween 80 was superior to bile salts and spans). Transfersomes were proved significantly superior in terms of, the amount of drug deposited in the skin and the amount permeated, with an enhancement ratio of 2.45, when compared to a marketed product. The study proved that the type and concentration of EA, as well as, the method of preparation had great influences on the properties of Transfersomes. Hence, optimized Transfersomes can significantly increase transepidermal flux and prolong the release of DS, when applied non-occlusively.