Quality by design (QbD) based approach for development of itraconazole loaded transferosomes for skin cancer: In vitro, ex vivo and cell line studies.

OBJECTIVE: Itraconazole (ITZ), a widely used systemic antifungal drug, has been ingeniously repurposed for its antitumor effects. In the present work, we have prepared and optimized the ITZ-loaded transferosomes by Quality by Design (QbD) approach and repurposed them for skin cancer. METHODS: The transferosomal formulation was optimized by employing a QbD approach with the design of experiment. A combination of screening and optimization design was used for formulation optimization. The optimized formulation was characterized by particle size, PDI, zeta potential, FTIR, XRD, and surface morphology using TEM. In vitro and ex vivo studies were performed using Franz diffusion cells. An in vitro cell line study was performed on the human melanoma A375 cell line. RESULTS: The optimized formulation has a particle size of 192.37 ± 13.19 nm, PDI of 0.41 ± 0.03, zeta potential -47.80 ± 3.66, and an entrapment efficiency of 64.11 ± 3.75%. In vitro release studies showed that ITZ encapsulated transferosomes offer higher and sustained release than pure drugs. Ex vivo drug penetration and retention studies show that the penetration and retention of transferosomes are more visible in the skin than in the drug. The cell viability study confirms that ITZ encapsulated transferosomes have almost 2-fold more potency against the A375 cell line than pure drug. CONCLUSION: ITZ encapsulated transferosomes were successfully prepared and optimized using a combination of screening and optimization designs. Based on ex vivo and cell line studies, we conclude that ITZ-loaded transferosomes could aid melanoma management alongside standard therapies.

Recombinant human epidermal growth factor-loaded liposomes and transferosomes for dermal delivery: Development, characterization, and cytotoxicity evaluation.

Recombinant human epidermal growth factor (rhEGF) is widely utilized as an antiaging compound in wound-healing therapies and cosmetic purposes. However, topical administration of rhEGF has limited treatment outcomes because of its poor percutaneous penetration and rapid proteinase degradation. To overcome these obstacles, this study aims to develop and characterize rhEGF-containing conventional liposomes (rhEGF-CLs) and transferosomes (rhEGF-TFs) as efficient dermal carriers. Physicochemical characterization such as particle size, zeta potential (ZP), morphology, encapsulation efficiency (EE%), and release properties of nanocarriers as well as in vitro cytotoxicity in human dermal fibroblast (HDF) and human embryonic kidney (HEK293) cell lines were investigated. rhEGF-TFs at the rhEGF concentration ranging from 0.05 to 1.0 µg/mL were chosen as the optimum formulation due to the desired release profile, acceptable EE%, optimal cell proliferation, and minimal cytotoxicity compared to the control and free rhEGF. However, higher concentrations caused a decrease in cell viability. The ratio 20:80 of Tween 80 to lipid was optimal for rhEGF-TFs-2, which had an average diameter of 233.23 ± 2.64 nm, polydispersity index of 0.33 ± 0.05, ZP of -15.46 ± 0.29 mV, and EE% of 60.50 ± 1.91. The formulations remained stable at 5°C for at least 1 month. TEM and SEM microscopy revealed that rhEGF-TFs-2 had a regular shape and unilamellar structure. In vitro drug release studies confirmed the superiority of rhEGF-TFs-2 in terms of optimal cumulative release of rhEGF approximately 82% within 24 h. Franz diffusion cell study showed higher rhEGF-TFs-2 skin permeation compared to free rhEGF solution. Taken together, we concluded that rhEGF-TFs can be used as a promising formulation for wound healing and skin regeneration products.

Liposomes like advanced drug carriers: from fundamentals to pharmaceutical applications.

AIMS: There are around 24 distinct lipid vesicles described in the literature that are similar to vesicular systems such as liposomes. Liposome-like structures are formed by combining certain amphiphilic lipids with a suitable stabiliser. Since their discovery and classification, self-assembled liposome-like structures as active drug delivery vehicles captured researchers' curiosity. METHODOLOGY: This comprehensive study included an in-depth literature search using electronic databases such as PubMed, ScienceDirect and Google Scholar, focusing on studies on liposome and liposomes like structure, discussed in literature till 2024, their sizes, benefits, drawback, method of preparation, characterisation and pharmaceutical applications. RESULTS: Pharmacosomes, cubosomes, ethosomes, transethosomes, and genosomes, all liposome-like structures, have the most potential due to their smaller size with high loading capacity, ease of absorption, and ability to treat inflammatory illnesses. Genosomes are futuristic because of its affinity for DNA/gene transport, which is an area of focus in today's treatments. CONCLUSION: This review will critically analyse the composition, preparation procedures, drug encapsulating technologies, drug loading, release mechanism, and related applications of all liposome-like structures, highlighting their potential benefits with enhanced efficacy over each other and over traditional carriers by paving the way for exploring novel drug delivery systems in the Pharma industry.

Unravelling the success of transferosomes against skin cancer: Journey so far and road ahead.

Skin cancer remains one of the most prominent types of cancer. Melanoma and non-melanoma skin cancer are commonly found together, with melanoma being the more deadly type. Skin cancer can be effectively treated with chemotherapy, which mostly uses small molecular medicines, phytoceuticals, and biomacromolecules. Topical delivery of these therapeutics is a non-invasive way that might be useful in effectively managing skin cancer. Different skin barriers, however, presented a major obstacle to topical cargo administration. Transferosomes have demonstrated significant potential in topical delivery by improving cargo penetration through the circumvention of diverse skin barriers. Additionally, the transferosome-based gel can prolong the residence of drug on the skin, lowering the frequency of doses and their associated side effects. However, the choice of appropriate transferosome compositions, such as phospholipids and edge activators, and fabrication technique are crucial for achieving improved entrapment efficiency, penetration, and regulated particle size. The present review discusses skin cancer overview, current treatment strategies for skin cancer and their drawbacks. Topical drug delivery against skin cancer is also covered, along with the difficulties associated with it and the importance of transferosomes in avoiding these difficulties. Additionally, a summary of transferosome compositions and fabrication methods is provided. Furthermore, topical delivery of small molecular drugs, phytoceuticals, and biomacromolecules using transferosomes and transferosomes-based gel in treating skin cancer is discussed. Thus, transferosomes can be a significant option in the topical delivery of drugs to manage skin cancer efficiently.

Fabrication and application of targeted ciprofloxacin nanocarriers for the treatment of chronic bacterial prostatitis.

Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 v/v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1ß, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.

Development of engineered transferosomal gel containing meloxicam for the treatment of osteoarthritis.

OBJECTIVE: .In this study, we investigated the potential of meloxicam (MLX) developed as transferosomal gel as a novel lipidic drug delivery system to address osteoarthritis (OTA), a degenerative joint disease that causes pain and stiffness. By incorporating meloxicam into a transferosomal gel, our aim was to provide a targeted and efficient delivery system capable of alleviating symptoms and slowing down the progression of OTA. MATERIAL AND METHODS: Classical lipid film hydration technique was utilized to formulate different transferosomal formulations. Different transferosomal formulations were prepared by varying the molar ratio of phospholipon-90H (phosphodylcholine) to DSPE (50:50, 60:40, 70:30, 80:20, and 90:10) and per batch, 80mg of total lipid was used. The quality control parameters such as entrapment efficiency, particle size and morphology, polydispersity and surface electric charge, in vitro drug release, ex vivo permeation and stability were measured. RESULTS: The optimized transferosomal formulations revealed a small vesicle size (121±12nm) and greater MLX entrapment (68.98±2.3%). Transferosomes mediated gel formulation MLX34 displayed pH (6.3±0.2), viscosity (6236±12.3 cps), spreadability (13.77±1.77 gm.cm/sec) and also displayed sustained release pattern of drug release (81.76±7.87% MLX released from Carbopol-934 gel matrix in 24h). MLX34 revealed close to substantial anti-inflammatory response, with ∼81% inhibition of TNF-α in 48h. Physical stability analysis concluded that refrigerator temperature was the preferred temperature to store transferosomal gel. CONCLUSION: MLX loaded transferosomes containing gel improved the skin penetration and therefore resulted into increased inhibition of TNF-α level.

Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma in situ.

Aims: This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with an enhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.

Despite progress, breast cancer remains a significant cause of death. This study aimed to revolutionize the treatment of noninvasive ductal carcinoma in situ, a type of breast cancer, by developing a special gel that can be applied directly to the breast. The developed gel was in the nanoform, a 'nanotransfersomal' gel that contained erlotinib, a potent drug for breast cancer. To ensure its effectiveness, we evaluated the erlotinib-loaded transfersomal gel through various tests. The results confirmed that the gel was nano-sized and loaded with a high amount of erlotinib. Animal studies were conducted to check if the prepared gel caused any skin irritation and interestingly, there was no irritation observed on the animals' skin. Furthermore, we treated breast cancer cells with the developed gel using a method called MTT assay and the results showed improved cell-killing activity in comparison to plain drug. In conclusion, this special gel represents a breakthrough in breast cancer treatment. It offers hope for better outcomes in the fight against this disease. This innovative approach involves directly applying the gel on the affected area topically to increase patient compliance and decreasing side effects of drugs. This could potentially transform ductal carcinoma in situ breast cancer treatment, bringing us closer to improved treatments and outcomes.

Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

A Comprehensive Review on Polyphenols Based Nanovesicular System for Topical Delivery.

BACKGROUND: Polyphenols are naturally occurring compounds having more than one hydroxy functional group. They are ubiquitous secondary plant metabolites possessing a wide range of pharmacological activity. Brightly colored fruits and vegetables are the natural source of polyphenols. Majorly, they possess antioxidant, anti-inflammatory and antimicrobial properties which make them suitable candidates to target skin related disorders. OBJECTIVE: This study is focused to explore the potential of polyphenols loaded nanovesicles for skin related disorders. The aim of the study is to review the applicability and efficacy of different vesicular systems encapsulated with various classes of polyphenols for skin related disorders, thus opening the opportunity for future studies based on these drug delivery systems. METHOD: Web of Science, PubMed, Scopus database, and the search engine Google Scholar were accessed for the literature search. The results were then filtered based on the titles, abstracts, and accessibility of the complete texts. RESULTS: The expository evaluation of the literature revealed that various nanovesicles like liposomes, niosomes, ethosomes and transferosomes incorporating polyphenol have been formulated to address issues pertaining to delivery across the skin. These developed nano vesicular systems have shown improvement in the physicochemical properties and pharmacological action. CONCLUSION: Polyphenol based nano-vesicular formulations have proved to be an effective system for topical delivery and henceforth, they might curtail the use of other skin therapies having limited applicability.

Transferosomes stabilized hydrogel incorporated rhodomyrtone-rich extract from Rhodomyrtus tomentosa leaf fortified with phosphatidylcholine for the management of skin and soft-tissue infections.

Rhodomyrtus tomentosa leaf (RT)-incorporated transferosomes were developed with lecithin and cholesterol blends with edge activators at different ratios. RT-transferosomes were characterized and employed in transferosomal gel formulations for the management of skin and soft-tissue infections. The optimized formulation entrapped up to 81.90 ± 0.31% of RT with spherical vesicles (405.3 ± 2.0 nm), polydispersity index value of 0.16 ± 0.08, and zeta potential of - 61.62 ± 0.86 mV. Total phenolic and flavonoid contents of RT-transferosomes were 15.65 ± 0.04 µg GAE/g extract and 43.13 ± 0.91 µg QE/g extract, respectively. RT-transferosomes demonstrated minimum inhibitory and minimum bactericidal concentrations at 8-256 and 64-1024 µg/mL, respectively. Free radical scavenging assay showed RT-transferosomes with high scavenging activity against DPPH and ABTS radicals. Moreover, RT-transferosomes demonstrated moderate activity against mushroom tyrosinase, with IC50 values of 245.32 ± 1.32 µg/mL. The biocompatibility results against L929 fibroblast and Vero cells demonstrated IC50 at 7.05 ± 0.17 and 4.73 ± 0.13 µg/mL, respectively. In addition, nitric oxide production significantly decreased by 6.78-88.25% following the treatment with 31.2-500 ng/mL RT-transferosomes (p < 0.001). Furthermore, the freeze-thaw stability study displayed no significant change in stability in the sedimentation and pH of gel fortified with RT-transferosomes. The results suggested that RT-transferosome formulation can be effectively employed as natural biomedicines for scar prevention and the management of skin soft-tissue infections.

Thyme Oil-Containing Fluconazole-Loaded Transferosomal Bigel for Transdermal Delivery.

The objective of the present research was to develop fluconazole-loaded transferosomal bigels for transdermal delivery by employing statistical optimization (23 factorial design-based). Thin-film hydration was employed to prepare fluconazole-loaded transferomal suspensions, which were then incorporated into bigel system. A 23 factorial design was employed where ratios of lipids to edge activators, lipids (soya lecithin to cholesterol), and edge activators (sodium deoxycholate to Tween 80) were factors. Ex vivo permeation flux (Jss) of transferosomal bigels across porcine skin was analyzed as response. The optimal setting for optimized formulation (FO) was A= 4.96, B= 3.82, and C= 2.16. The optimized transferosomes showed 52.38 ± 1.76% DEE, 76.37 nm vesicle size, 0.233 PDI, - 20.3 mV zeta potential, and desirable deformability. TEM of optimized transferosomes exhibited a multilamelar structure. FO bigel's FE-SEM revealed a globule-shaped vesicular structure. Further, the optimized transferosomal suspension was incorporated into thyme oil (0.1% w/w)-containing bigel (TO-FO). Ex vivo transdermal fluconazole permeation from different transferosomal bigels was sustained over 24 h. The highest permeation flux (4.101 µg/cm2/h) was estimated for TO-FO bigel. TO-FO bigel presented 1.67-fold more increments of antifungal activity against Candida albicans than FO bigel. The prepared thyme oil (0.1% w/w)-containing transfersomal bigel formulations can be used as topical delivery system to treat candida related fungal infections.

Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2.

Purpose: Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs. Methods: Transferosomes were developed by using 33 screening layouts. The phospholipid concentration as well as the concentration and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels. Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay (CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits. Results: The optimized preparation displayed a particle size of 664.3 ± 69.3 nm, EE% of 82.8 ± 0.02%, ZP of -11.23 ± 2.5 mV, and PDI of 0.6 ± 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively high lung accumulation after intranasal administration. Conclusion: This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated further in preclinical and clinical studies.

Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model.

Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER's antidepressant activity, a QER-loaded transferosome (QER-TFS) thermosensitive gel for intranasal administration was formulated and optimized. The therapeutic effectiveness of the optimized formulation was assessed in a depressed rat model by conducting a behavioral analysis. Behavioral study criteria such as immobility, swimming, climbing, sucrose intake, number of crossed lines, rearing, active interaction, and latency to feed were all considerably enhanced by intranasal treatment with the QER-TFS in situ gel in contrast to other formulations. A nasal histopathological study indicated that the QER-TFS thermosensitive gel was safe for the nasal mucosa. An immunohistochemical analysis showed that the animals treated with the QER-TFS thermosensitive gel had the lowest levels of c-fos protein expression, and brain histopathological changes in the depressed rats were alleviated. According to pharmacodynamic, immunohistochemical, and histopathological experiments, the intranasal administration of the QER-TFS thermosensitive gel substantially alleviated depressive symptoms in rats. However, extensive preclinical investigations in higher animal models are needed to anticipate its effectiveness in humans.

Improved skin permeation of transferosomes containing Eulophia macrobulbon extract.

Eulophia macrobulbon (EM) extract-loaded transferosomes represent an advanced approach for enhancing skin permeation of bioactive compounds. The formulations improving skin permeation and characterizations of transferosomes were studied, including morphology, entrapment efficiency (EE), vesicle size, polydispersity index (PDI), zeta potential, and skin permeation in the Strat-M® synthetic membrane. Vesicle size increased with increasing transition temperature (Tm) of phosphatidylcholine and the hydrophilic-lipophilic balance (HLB) of the surfactant used as an edge activator. EM extract-loaded transferosomes with varying amounts of phosphatidylcholine, surfactants, and EM extract showed non-significant differences in EE, PDI, and zeta potential. The results demonstrated that the EM extract-loaded transferosomes improved membrane permeability better than the EM solution. The EM solution exhibited a shorter lag time. Considering the advantages of the EM extract-loaded transferosomes and EM solutions, a combination of both formulations was developed in this study. The results showed that the lag time decreased and membrane permeation increased. This study highlights a novel system combining EM extract-loaded transferosomes and an EM solution, exhibiting considerable improvement in skin permeation and presenting the potential for an efficient transdermal drug delivery system for natural bioactive compounds.

Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: I. Optimization, Characterization, Brain Localization, and Cytotoxic Studies.

Numerous neurological disorders have a pathophysiology that involves an increase in free radical production in the brain. Quercetin (QER) is a nutraceutical compound that shields the brain against oxidative stress-induced neurodegeneration. Nonetheless, its low oral bioavailability diminishes brain delivery. Therefore, the current study aimed to formulate QER-loaded transferosomal nanovesicles (QER-TFS) in situ gel for QER brain delivery via the intranasal route. This study explored the impacts of lipid amount, edge activator (EA) amount, and EA type on vesicle diameter, entrapment, and cumulative amount permeated through nasal mucosa (24 h). The optimum formulation was then integrated into a thermosensitive gel after its physical and morphological characteristics were assessed. Assessments of the optimized QER-TFS showed nanometric vesicles (171.4 ± 3.4 nm) with spherical shapes and adequate entrapment efficiency (78.2 ± 2.8%). The results of short-term stability and high zeta potential value (-32.6 ± 1.4 mV) of QER-TFS confirmed their high stability. Compared with the QER solution, the optimized QER-TFS in situ gel formulation exhibited sustained release behavior and augmented nasal mucosa permeability. CT scanning of rat brains demonstrated the buildup of gold nanoparticles (GNPs) in the brains of all treatment groups, with a greater level of GNPs noted in the rats given the transferosomal gel. Additionally, in vitro studies on PCS-200-014 cells revealed minimal cytotoxicity of QER-TFS in situ gel. Based on these results, the developed transferosomal nanovesicles may be a suitable nanocarrier for QER brain targeting through the intranasal route.

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. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses suggest 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 exposure.Inizio modulo.

Fabrication, Optimization, and Evaluation of Transdermal Patch: As an Alternative and Effective Transdermal Delivery System for Nebivolol HCl.

BACKGROUND: Nebivolol HCl is a unique third-generation beta blocker that has less oral bioavailability and exhibits various adverse effects like gastrointestinal disturbance and abdominal pain. OBJECTIVE: This study aimed to formulate and evaluate nebivolol HCl transferosomal transdermal patches to reduce the problems associated with oral delivery of the drug and enhancement of drug permeation through the skin. METHODS: Nebivolol HCl loaded transferosomes were prepared by thin film hydration method. Eight formulations were prepared based on the two independent variables, type of surfactant (Tween 80 and Span 80) and Phospholipid: Edge activator ratio and were evaluated for their vesicle size, PDI, and entrapment efficiency. The optimized formulations were incorporated into transdermal patches, which were evaluated for physicochemical properties, in-vitro and ex-vivo permeation, skin irritancy, and stability studies. RESULTS: The vesicle size of the transferosomes ranged from 49nm to 93nm, and EE% varied from 39% to 79%. Vesicles formed with Span 80 as an edge activator showed smaller vesicle size and greater EE% as compared to Tween 80. Based on the results, TW4 and SP4 were selected as the optimized formulations for further incorporation into the transdermal patches. In-vitro and ex-vivo permeation studies showed permeation in the order F2 > F3 > F1, indicating that transferosomal formulations showed superior permeation of the drug compared to plain Nebivolol HCl patches. Span 80 transferosomes showed a slightly better permeation than Tween 80. Stability studies showed that transferosomes and the transdermal patches demonstrated good stability under proper storage conditions. CONCLUSION: The study concluded that transferosomal patches of Nebivolol HCl could be used as a potential approach with effective transdermal delivery for the management of hypertension.

DOE-Assisted Formulation, Optimization, and Characterization of Tioconazole-Loaded Transferosomal Hydrogel for the Effective Treatment of Atopic Dermatitis: In Vitro and In Vivo Evaluation.

The present study was performed to determine the therapeutic effects of tioconazole (Tz)-loaded novel transferosome carriers (TFs) for the treatment of atopic dermatitis (AD). METHOD: Tioconazole transferosomes suspension (TTFs) was formulated and optimized using a 32 factorial design. After that, the optimized batch of TTFs loaded into Carbopol 934 and sodium CMC was prepared with hydrogel and noted as TTFsH. Subsequently, it was evaluated for pH, spread ability, drug content, in vitro drug release, viscosity, in vivo scratching and erythema score, skin irritation, and histopathology study. RESULT: The optimized batch of TTFs (B4) showed the values of vesicle size, flux, and entrapment efficiency to be 171.40 ± 9.03 nm, 48.23 ± 0.42, and 93.89 ± 2.41, respectively. All batches of TTFsH showed sustained drug release for up to 24 h. The F2 optimized batch released Tz in an amount of 94.23 ± 0.98% with a flux of 47.23 ± 0.823 and followed the Higuchi kinetic model. The in vivo studies provided evidence that the F2 batch of TTFsH was able to treat atopic dermatitis (AD) by reducing the erythema and the scratching score compared to that of the marketed formulation (Candiderm cream, Glenmark). The histopathology study supported the result of the erythema and scratching score study with intact skin structure. It showed that a formulated low dose of TTFsH was safe and biocompatible to both the dermis and the epidermis layer of skin. CONCLUSION: Thus, a low dose of F2-TTFsH is a promising tool that effectively targeted the skin for the topical delivery of Tz to treat atopic dermatitis symptoms.

Unraveling the pharmaceutical and clinical relevance of the influence of syringic acid loaded linoleic acid transferosomes on acne.

Natural medicines are promising platforms for competent topical treatment modalities benefiting the cosmetic implementation and proffering solutions to the current remedies. Therefore, the objective of this study was to formulate syringic acid (SA), well-known for its multilateral anti-inflammatory, antimicrobial and antioxidant potentials, in newly developed linoleic acid (LA) transferosomes as an anti-acne nano-form remedy. Herein, LA was incorporated in transferosomes owing to its antimicrobial effect and dermal penetrability. Comprehensive appraisal through physicochemical, antioxidant and dermal deposition investigations was conducted. Clinical assessment was also performed in acne patients and compared with the marketed product (Adapalene® gel). The relevant investigations of the optimum formula indicated stable vesicles with a small-sized diameter (147.46 nm), surface charge (-26.86 mV), spherical architecture, reasonable entrapment (76.63%), considerable antioxidant activity (IC50 = 11.1 µg/mL) and remarkable skin deposition (78.72%).More importantly, LA based transferosomes enclosing SA exhibited inflammation lessening in acne sufferers as manifested by greater reduction in the total count of the acne lesions reaching 79.5% in contrast to Adapalene® gel with only 18.7% reduction in acne lesions. Interestingly, no irritation and erythema were reported for the proposed transferosomes. Inclusively, the cosmetic formulation practice could reap benefits of the development of such vesicles.

Skin drug delivery using lipid vesicles: A starting guideline for their development.

Lipid vesicles can provide a cost-effective enhancement of skin drug absorption when vesicle production process is optimised. It is an important challenge to design the ideal vesicle, since their properties and features are related, as changes in one affect the others. Here, we review the main components, preparation and characterization methods commonly used, and the key properties that lead to highly efficient vesicles for transdermal drug delivery purposes. We stand by size, deformability degree and drug loading, as the most important vesicle features that determine the further transdermal drug absorption. The interest in this technology is increasing, as demonstrated by the exponential growth of publications on the topic. Although long-term preservation and scalability issues have limited the commercialization of lipid vesicle products, freeze-drying and modern escalation methods overcome these difficulties, thus predicting a higher use of these technologies in the market and clinical practice.