Skin Permeation Research Articles

In vitro human skin absorption of ethyl salicylate, pentyl salicylate, and (Z)-3-hexenyl salicylate from topical formulations: Effects on permeation and distribution.

In vitro human skin permeation and distribution of the fragrance materials ethyl salicylate (CAS 118-61-6, ES), (Z)-3-hexenyl salicylate (CAS 65405-77-8, HS) and pentyl salicylate (CAS 2050-08-0, PS) from separate 0.5 % (w/w) cream formulations were determined under unoccluded and occluded conditions for 24 h. For PS only, a 0.5 % (w/v) solution in 70/30 (v/v) ethanol/water was also assessed. Consumer relevant finite formulation doses were applied (5 mg/cm2 or 5 μl/cm2) with salicylate application of ~25 μg/cm2. Although specifically assessing metabolism was not an aim, the common hydrolysis product salicylic acid (SA) was also quantified and included in overall test compound absorption values. For ES, absorbed doses (mean ± standard error, SE) were 12.0 ± 1.0 and 24.7 ± 1.3 % applied dose under unoccluded and occluded conditions, respectively. For HS these values were 7.28 ± 0.52 and 11.1 ± 0.7 % applied dose. For the PS cream, corresponding values were 4.43 ± 0.48 and 7.52 ± 0.63 % applied dose. Whilst for the PS solution values were 8.26 ± 0.31 and 16.1 ± 0.7 % applied dose. The salicylate structure, application vehicle and level of occlusion impacted on the observed skin absorption. Considering salicylates are commonly used fragrance ingredients and have limited skin absorption data, the current research will be helpful in risk assessment to determine systemic exposure that is realistic and fill data gaps.

Assessment of in vitro skin permeation and accumulation of phenolic acids from honey and honey-based pharmaceutical formulations

BackgroundHoney has been successfully used in wound care and cosmetics because of its effective biological properties, including antibacterial, antioxidant, and anti-inflammatory activities. Polyphenols, particularly phenolic acids, are key honey components responsible for these beneficial effects. In recent years, there has been a growing demand for natural, ecologically friendly, and biodegradable products in the modern cosmetics and wound care market. This study aimed to identify and quantify phenolic acids in four Polish honey samples of different botanical origins (heather, buckwheat, linden and rapeseed) and to assess for the first time the permeation of the identified phenolic acids through the skin and their accumulation after the application of pure honey samples, as well as honey-based hydrogel and emulsion formulations.MethodsThe honey samples’ antioxidant activity and total phenolic content were determined using the DPPH and ABTS assays and the Folin–Ciocalteu method, respectively. Phenolic acids and volatile compounds were identified and quantified in honey samples using the HPLC-UV and GC-MS method, respectively. The biocompatibility of the honey samples was evaluated using a murine fibroblast cell line (L929). A Franz-type vertical diffusion cell with porcine skin was used to assess phenolic acid’s permeation and skin accumulation from different honey-based pharmaceutical formulations. The biodegradability of the prepared formulations was also characterised.ResultsGallic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, coumaric acid, and 3-hydroxybenzoic acid were identified and quantified in the honey samples. Heather honey exhibited significantly higher antioxidant activity and total polyphenol content than the other honey samples. Heather, linden and buckwheat honey samples significantly decreased cell viability at concentrations of 5% and 2.5%, while rapeseed honey sample markedly reduced fibroblast viability only at 5%. Among the tested formulations - pure honey, hydrogel, and emulsion - higher skin permeation and accumulation rates of phenolic acids were observed with the prepared honey-based hydrogels than with the pure honeys and emulsions. Additionally, the prepared formulations were classified as partially biodegradable.ConclusionsThe obtained results confirmed the effectiveness of two pharmaceutical formulations in the form of a hydrogel or emulsion containing honey after applied topically. The inclusion of honey in the vehicle, in particular hydrogel increased the penetration of phenolic acids through the skin.

In Vitro Drug Release and Ex Vivo Dermal Drug Permeation Studies of Selected Commercial Benzoyl Peroxide Topical Formulations: Correlation Between Human and Porcine Skin Models.

In vitro release testing (IVRT) serves as a crucial tool to assess the quality, physicochemical behavior, and performance of semisolid formulations already available on the market. In vitro skin permeation studies (IVPT) are widely used to evaluate the safety and efficacy profiles of topical drugs, utilizing biological membranes prepared from ex vivo human and porcine skin tissues. This study aimed to develop and validate a discriminative IVRT method to evaluate various marketed topical benzoyl peroxide formulations. Additionally, IVPT was employed to assess skin permeation and retention profiles of these formulations, comparing porcine skin results with those obtained by using ex vivo human skin tissues. Physicochemical differences among the evaluated benzoyl peroxide formulations were identified, with the poloxamer-based formulation exhibiting a higher release rate. IVPT using both porcine and human skin differentiated retention and skin permeation profiles, with the poloxamer-based formulation demonstrating greater skin retention capacity compared to the other formulations evaluated. Similar conclusions on benzoyl peroxide retention and cutaneous permeation were drawn from both porcine and human skin IVPT tests, confirming the correlation between the two models.

Insights into Dermal Permeation of Skin Oil Oxidation Products from Enhanced Sampling Molecular Dynamics Simulation.

The oxidation of human sebum, a lipid mixture covering our skin, generates a range of volatile and semivolatile carbonyl compounds that contribute largely to indoor air pollution in crowded environments. Kinetic models have been developed to gain a deeper understanding of this complex multiphase chemistry, but they rely partially on rough estimates of kinetic and thermodynamic parameters, especially those describing skin permeation. Here, we employ atomistic molecular dynamics simulations to study the translocation of selected skin oil oxidation products through a model stratum corneum membrane. We find these simulations to be nontrivial, requiring extensive sampling with up to microsecond simulation times, in spite of employing enhanced sampling techniques. We identify the high degree of order and stochastic, long-lived temporal asymmetries in the membrane structure as the leading causes for the slow convergence of the free energy computations. We demonstrate that statistical errors due to insufficient sampling are substantial and propagate to membrane permeabilities. These errors are independent of the enhanced sampling technique employed and very likely independent of the precise membrane model.

Optimized Mesoporous Silica Nanoparticles for Delivery of Curcumin and Quercetin: Enhanced Skin Permeation and Cytotoxicity Against A375 Melanoma Cells

Optimized Mesoporous Silica Nanoparticles for Delivery of Curcumin and Quercetin: Enhanced Skin Permeation and Cytotoxicity Against A375 Melanoma Cells

AI-Driven Innovation in Skin Kinetics for Transdermal Drug Delivery: Overcoming Barriers and Enhancing Precision

Transdermal drug delivery systems (TDDS) offer an alternative to conventional oral and injectable drug administration by bypassing the gastrointestinal tract and liver metabolism, improving bioavailability, and minimizing systemic side effects. However, widespread adoption of TDDS is limited by challenges such as the skin’s permeability barrier, particularly the stratum corneum, and the need for optimized formulations. Factors like skin type, hydration levels, and age further complicate the development of universally effective solutions. Advances in artificial intelligence (AI) address these challenges through predictive modeling and personalized medicine approaches. Machine learning models trained on extensive molecular datasets predict skin permeability and accelerate the selection of suitable drug candidates. AI-driven algorithms optimize formulations, including penetration enhancers and advanced delivery technologies like microneedles and liposomes, while ensuring safety and efficacy. Personalized TDDS design tailors drug delivery to individual patient profiles, enhancing therapeutic precision. Innovative systems, such as sensor-integrated patches, dynamically adjust drug release based on real-time feedback, ensuring optimal outcomes. AI also streamlines the pharmaceutical process, from disease diagnosis to the prediction of drug distribution in skin layers, enabling efficient formulation development. This review highlights AI’s transformative role in TDDS, including applications of models such as Deep Neural Networks (DNN), Artificial Neural Networks (ANN), BioSIM, COMSOL, K-Nearest Neighbors (KNN), and Set Covering Machine (SVM). These technologies revolutionize TDDS for both skin and non-skin diseases, demonstrating AI’s potential to overcome existing barriers and improve patient care through innovative drug delivery solutions.

Formulation and clinical evaluation of hyaluronic acid nanogel in treatment of tear trough: nano-flipping from injectable fillers to topical nanofillers

Tear trough deformity (TTD) is a significant cosmetic concern, with current treatments relying primarily on invasive injectable fillers, which are costly and carry risks of complications. Despite the widespread use of hyaluronic acid (HA) in cosmetic applications, its poor dermal permeation has limited the development of effective topical fillers for TTD. This study aim to develop and evaluate a novel hyaluronic acid nanogel (nanofiller, NF) as a non-invasive topical filler for TTD. The hyaluronic acid NF was formulated and characterized for size, zeta potential, and skin permeation using the Franz diffusion method. The nanofiller demonstrated a particle size of 213.28 ± 4.15 nm and a zeta potential of −22.1 ± 1.07 mV, with a tenfold superior permeation compared to conventional HA gel. Thirty adult female patients aged 21–50 years with TTD were enrolled in a clinical trial and randomly assigned to receive either the NF or a conventional HA gel (control). Participants were randomly assigned to receive either the NF or a conventional HA gel (control). Clinical evaluation included subjective assessments and objective photomorphometric measurements of TTD parameters such as skin roughness (fine lines), indentation index, mean density, and percentage of the affected area. The NF group showed a significant improvement in TTD parameters, including up to a 40-fold reduction in skin roughness and indentation index, with 100% patient satisfaction and no adverse effects, compared to the control group. "To conclude; this study demonstrates the efficacy and safety of the HA nanofiller as the first effective topical treatment for TTD, offering a non-invasive alternative to injectable fillers.

Overcoming Skin Barrier with Transfersomes: Opportunities, Challenges, and Applications.

Transdermal drug delivery systems (TDDS) offer several advantages over traditional methods like injections and oral administration, including preventing first-pass metabolism, providing consistent and sustained activity, reducing side effects, enabling the use of short halflife drugs, improving physiological response, and enhancing patient convenience. However, the permeability of skin poses a challenge for TDDS, as it is impermeable to large molecules and hydrophilic drugs but permeable to small molecules and lipophilic medications. To overcome this barrier, researchers have investigated vesicular systems, such as transfersomes, liposomes, niosomes, and ethosomes. Among these vesicular systems, transfersomes are particularly promising for non-invasive drug administration due to their deformability and flexible membrane. They have been extensively studied for delivering anticancer drugs, insulin, corticosteroids, herbal medicines, and NSAIDs through the skin. Transfersomes have demonstrated efficacy in treating skin cancer, improving insulin delivery, enhancing site-specific corticosteroid delivery, and increasing the permeation and therapeutic effects of herbal medicines. They have also been effective in delivering pain relief with minimal side effects using NSAIDs and opioids. Transfersomes have been used for transdermal immunization and targeted drug delivery, offering site-specific release and minimizing adverse effects. Overall, transfersomes are a promising approach for transdermal drug delivery in various therapeutic applications. The aim of the present review is to discuss the various advantages and limitations of transfersomes and their mechanism to penetration across the skin, as well as their application for the delivery of various drugs like anticancer, antidiabetic, NSAIDs, herbal drugs, and transdermal immunization. Data we searched from PubMed, Google Scholar, and ScienceDirect. In this review, we have explored the various methods of preparation of transferosomes and their application for the delivery of various drugs like anticancer, antidiabetic, NSAIDs, herbal drugs, and transdermal immunization. In comparison to other vesicular systems, transfersomes are more flexible, have greater skin penetration capability, can transport systemic medicines, and are more stable. Transfersomes are capable of delivering both hydrophilic and hydrophobic drugs, making them suitable for transdermal drug delivery. The developed transfersomal gel could be used to improve medicine delivery through the skin.

Transdermal delivery of Acheta domesticus protein hydrolysate using nanostructured lipid carriers and Derma Stamp ― Does the combination of lipid-based formulation and a physical technique add value for permeation and retention?

Acheta domesticus protein hydrolysate (PH) is a natural anti-skin aging compound, but its effectiveness is hindered by poor skin penetration due to its hydrophilicity and high molecular weight. This study aimed to compare the enhancement of PH skin delivery by increasing lipophilicity with nanostructured lipid carriers (NLCs) and bypassing the skin barrier using physical techniques, including Derma Stamp and dissolving microneedles (MNs). Fluorescein isothiocyanate (FITC)-tagged PH was prepared to track the transdermal transport, and complexed with dioctyl sodium sulfosuccinate (DSS) to be encapsulated into NLCs, prepared using a melt emulsification method. Skin delivery was evaluated in terms of skin permeation and skin retention using Franz diffusion cells. The FITC-PH loaded NLCs had a particle size of 238.9 ± 0.8 nm, a polydispersity index of 0.3 ± 0.0, a zeta potential of −23.6 ± 1.0 mV, and an encapsulation efficiency of 65.1 ± 2.1%. The MNs, prepared with polyvinylpyrrolidone K30 and polyvinyl alcohol (38:15 weight ratio), had uniform sharp needles and a high FITC-PH loading capacity of 97.2 ± 1.9%. PH permeation was most effectively enhanced through physical barrier bypassing, particularly with the Derma Stamp, followed by MNs and finally due to incorporation into NLCs. Notably, when utilizing the Derma Stamp, converting the aqueous solution of PH into an NLC formulation added positive benefits by significantly improving skin retention. In conclusion, it was suggested that while physical enhancement methods are crucial for permeation of the PH, optimizing formulation characteristics, such as incorporation into NLCs, further increased the overall effectiveness of skin delivery.

CD44-targeted hyaluronic acid coated imiquimod lipid nanocapsules foster the efficacy against skin cancer: Attempt to conquer unfavorable side effects.

This study was executed to mitigate imiquimod (IMQ)-side effects and promote its anticancer potential against skin cancer via encapsulation in hyaluronic acid-coated lipid nanocapsules (HA-LNCs) for targeted topical delivery. The LNCs were prepared using the phase inversion technique. Optimized LNCs formulation was gained following 22 factorial design experiment to adjust the IMQ and CTAB concentrations. The two variables were found to significantly influence the dependent responses. The encapsulation efficiency of IMQ exceeded 97%. HA coating provided a sustained release of IMQ from LNCs, with 63.81±2.45% of IMQ released after 24h. Moreover, the ex-vivo human skin permeation study showed that 7.9-fold more IMQ was localized in all skin layers than that permeated. In vitro anticancer activity indicated that IMQ-HA-LNCs had higher cytotoxicity (IC50=22.39μg/mL) compared to free IMQ (IC50=97.94μg/mL). Further, in vivo studies revealed that encapsulation of IMQ in HA-LNCs enhanced its immunostimulatory potential and promoted its anti-tumor activity in competing skin cancer even in low doses compared to the untreated group and group treated with a brand product with no topical or systemic toxicity. The present study suggested that HA-LNCs with their mixed polymeric/lipophilic nature epitomize a promising strategy for safe topical delivery of poorly water-soluble candidates.

Design and characterization of κ-Carrageenan:PVA hydrogels to repurpose the topical delivery of betamethasone.

Atopic dermatitis (AD) is a severe inflammatory skin disorder, affecting children and adults worldwide, and despite the several existing treatments, it is necessary to find new alternative topical therapies. Hydrogels may represent a good tool to treat AD due to their high water content, making them excellent candidates for drug delivery vehicles in skin research. This work aimed to develop and characterize hybrid hydrogels composed of gel-forming polymers (k-carrageenan and polyvinyl alcohol) for cutaneous delivery of betamethasone (up to 0.2 mg mL-1) widely used to manage AD, with high skin retention. Bergamot oil and menthol essential oils were also incorporated into the hydrogels to study their effects on penetration and retention of the corticosteroid. Rheological properties revealed the pseudoplastic behavior of the hydrogels, a favorable characteristic for skin application. Cytocompatibility towards fibroblasts and keratinocytes was determined, revealing safe usage of the hydrogel blends up to 100 mg mL-1, corresponding to 20 µg mL-1 in betamethasone, but was compromised by the presence of the essential oils in the higher hydrogel tested concentrations (50 and 100 mg mL-1). The ex vivo pig ear skin permeation assay showed that hydrogels promote betamethasone retention up to 20 % of the added dose (c.a. 10 µg) even after 24 h of permeation, independently of the use of essential oils' use in the composition, showing that they might be a good strategy to treat AD skin.

The role of biophysical properties in defining the functional applications of alkyl esters of L-ascorbic acid.

Lipophilic derivatives of vitamin C, known as ascorbyl-6-O-alkanoates (ASCn), have been mainly developed for use in cosmetics, pharmaceuticals, and the food industry as antioxidant additives. These derivatives are of biotechnological interest due to their antioxidant properties, amphiphilic behavior, capacity to self-organize into nano- and micro-structures, anionic nature, and low cost of synthesis. In this review, we will focus on the commercial amphiphile, 6-O-palmitoyl L-ascorbic acid (ASC16), and the shorter acyl chains derivatives, such as 6-O-myristoyl (ASC14) and 6-O-lauroyl L-ascorbic acid (ASC12). The biophysical characteristics of the ASCn family members make them promising candidates for applications such as antioxidant additives, drug carriers in topical pharmaceutical formulations, skin permeation enhancers, and vaccine adjuvants. Furthermore, they exhibit antimicrobial and antibiofilm activities, drawing attention from new biotechnology frontiers. By exploring the biophysical properties of ASCn derivatives, this review highlights their potential applications and the fundamental mechanisms driving their functionality.

Serine-modified silver nanoparticle porous spray membrane: A novel approach to wound infection prevention and inflammation reduction.

Traditional wound care preparations frequently face challenges such as complex care protocols, poor patient compliance, limited skin permeability, lack of aesthetics, and inconvenience, in addition to the risk of bacterial infection. We developed a spray film preparation containing nanocellulose and L-serine modified nanosilver, capable of rapidly forming a transparent film on the skin within minutes of application. The incorporation of nanocellulose imparted protective, moisturizing, and breathable properties to the film, allowing for easy removal after use. Moreover, our innovative application of L-serine as a precursor for synthesizing silver nanoparticles not only overcomed the limitations of current silver nanoparticle synthesis methods but also enhanced antibacterial efficacy by leveraging the inherent antimicrobial properties and bacterial targeting capability of L-serine. Specifically, the addition of nanocellulose to the spray film forming system enhanced air permeability and drug carrying capacity by creating a lightweight porous structure, while also ensuring the antimicrobial and anti-inflammatory efficacy of serine modified silver nanoparticles. Mice treated with spray film formulations containing nanocellulose and silver nanoparticles demonstrated superior wound healing, normalization of keratin thickness, increased hair follicle count, and reduced inflammatory markers. In conclusion, our study developed a spray film that integrated excellent antimicrobial properties with user convenience. This research presented innovative strategies for clinical wound care, antibacterial infection management, and post laser cosmetic treatment, with the potential to substantially enhance wound care in practical application.

A novel quercetin-phospholipid complex gel for enhanced skin permeability and photoprotection - Ex vivo and in vivo studies

A novel quercetin-phospholipid complex gel for enhanced skin permeability and photoprotection - Ex vivo and in vivo studies

Dual-strategy microneedles of bio‑oxygen therapy and artificial enzyme anti-oxidation for psoriasis treatment.

Oxidative stress results from an imbalance between the production of free radicals by oxidants and their removal by antioxidants. Chronic oxidative stress is a key factor in inflammation, characterized by hypoxic microenvironments and elevated levels of reactive oxygen species (ROS). Psoriasis, a common chronic inflammatory skin disorder, profoundly impacts the physical and psychological well-being of affected individuals. In response to this, we have innovatively developed a core-shell structured Chlorella-Prussian Blue Complex (Z-PB), integrating dual therapeutic strategies of biological oxygen therapy and oxidative stress regulation to address psoriasis. The Z-PB leveraged the unique ability of Chlorella to generate dissolved oxygen under light, combined with the broad enzymatic activity of Prussian Blue (PB), to effectively ameliorate the oxidative stress in the chronic inflammatory microenvironment. Additionally, the Z-PB overcame challenges such as the survival of Chlorella in high ROS environments and the aggregation of nanoenzymes. The Z-PB-loaded hyaluronic acid microneedles (Z-PBHA/MNs) demonstrated excellent skin permeability, in vitro release profiles, and biocompatibility. These Z-PBHA/MNs had been shown to alleviate psoriasis induced by imiquimod (IMQ). Overall, the Z-PBHA/MNs incorporating both biological oxygen therapy and artificial enzyme antioxidants represented a promising and innovative therapeutic strategy for the treatment of psoriasis.

Potential of the Nano-Encapsulation of Antioxidant Molecules in Wound Healing Applications: An Innovative Strategy to Enhance the Bio-Profile

Naturally available antioxidants offer remarkable medicinal applications in wound healing. However, the encapsulation of these phytoactive moieties into suitable nano-scale drug delivery systems has always been challenging due to their inherent characteristics, such as low molecular weight, poor aqueous solubility, and inadequate skin permeability. Here, we provide a systematic review focusing on the major obstacles hindering the development of various lipid and polymer-based drug transporters to carry these cargos to the targeted site. Additionally, this review covers the possibility of combining the effects of a polymer and a lipid within one system, which could increase the skin permeability threshold. Moreover, the lack of suitable physical characterization techniques and the challenges associated with scaling up the progression of these nano-carriers limit their utility in biomedical applications. In this context, consistent progressive approaches for addressing these shortcomings are introduced, and their prospects are discussed in detail.

Hair follicle targeting via gelatin coated transferosomes loaded with tofacitinib citrate for enhanced treatment of alopecia areata: Clinical evaluation of alopecia areata patients.

Alopecia areata (AA) is a complex autoimmune disease that has a negative impact on the psychological well-being of patients. AA is associated with T-cells activation and cytokines release leading to collapse of immune privilege of hair follicles (HF). Tofacitinib, a JAK 1&3 inhibitor, exhibited effectiveness in AA treatment. The aim of this study was to develop gelatin-coated transferosomes (GLTS) to deliver tofactinib specifically to the HF to enhance the treatment of AA. GLTS were evaluated for ex vivo skin permeation, localization in skin layers by the tape stripping technique and Confocal microscopy. Finally, GLTS gel was applied topically for the treatment of AA patients, where seven AA patients with recalcitrant lesions (5 males and 2 females) were included in this study, then they were evaluated clinically and dermoscopically to assess the efficacy of treatment. GLTS of size 223.23 ± 16.43 nm, exhibited the highest HF localization by tape stripping (7.8561 ± 0.77 μg), and the highest mean fluorescence intensity in HF (84.63 ± 7.98 rfu). Additionally, hair regrowth in all AA patients was observed after 12 weeks with up to 80 % improvement. The present work proposed effective formulations for HF targeting of tofacitinib and proved enhanced clinical efficacy in recalcitrant AA patients with positive feedback.

Topical delivery performance of Pickering emulsions stabilized by differently charged spirulina protein isolate/Chitosan composite particles.

Pickering emulsions, stabilized by particulate particles, have emerged as a promising vehicle for topical delivery. Herein, Pickering emulsions stabilized by differently charged spirulina protein isolate - chitosan (SC) composite particles were studied for effective topical delivery of α-Bisabolol (ABS). The composite particles were synthesized via electrostatic assembly of spirulina protein isolate (SPI) and chitosan (CS), and their surface charge was assessed using zeta potential measurements. The Pickering emulsions stabilized by SC composite particles with different charges were all stable over 30 days and had a high encapsulation efficiency for ABS. In vitro skin permeation study revealed that positively charged emulsions significantly increased ABS retention within the skin, predominantly in the stratum corneum layer. The underlying delivery mechanism was further explored using attenuated total reflection Fourier transform infrared spectroscopy. Lastly, the influence of particle concentration and oil phase volume fraction on the topical delivery efficiency was conducted to optimize the Pickering formulations. This study provides insight into the role of particle charge in enhancing topical delivery of Pickering emulsions.

Skin microincision technique to enhance drug penetration for the treatment of keloid and hypertrophic scars.

The synergistic effect of corticosteroids and 5-fluorouracil (5-FU) for the treatment of pathological scarring is widely documented. While topical administration can be a painless, convenient way to convey the two active ingredients, physical enhancement techniques such as microneedling are required to deepen their skin penetration and achieve therapeutic effects. A novel approach to keloid and scar treatment is given by microincision, i.e., micrometric-sized columnar perforations which allow the drugs to diffuse into the skin and promote tissue proliferation in a more physiological structure. Combining the delivery of triamcinolone acetonide (TAC) and 5-FU with microincision is an innovative approach that could improve the speed and efficacy of regenerative treatments. This study evaluated the effectiveness of the skin treatment with a device combining microincisions and photobiomodulation, in the skin permeation of a combination of TAC and 5-FU. Increasing treatment times (4, 6, and 8 min) led to higher drug penetration compared to intact skin, with a more noticeable effect for 5-FU compared to TAC. Specifically, all treatment durations were significantly more effective (p < 0.05) than the control for 5-FU, while TAC showed less variation between treatments. Moreover, it was shown that in-vitro the permeation improvement given by the red-light treatment was mainly due to the mechanical massage which pushed the actives into the microchannels created by the treatment. The application of prolonged skin microincision times ensured much higher skin permeation of both TAC and 5-FU compared to microneedling on healthy excised skin.

Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule based hydrogel for transdermal delivery.

Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule hydrogel for transdermal delivery. A 33 Box-Behnken Design and numerical optimization was performed to obtain the optimized formulation. Subsequently, the optimized raloxifene hydrochloride loaded lipid nanocapsule was developed using phase inversion temperature and characterized for physicochemical properties. Furthermore, the optimized lipid nanocapsule was loaded into a hydrogel and evaluated for rheology, spreadability, ex-vivo skin permeation, deposition and irritation. The numerical optimization suggested an optimal formula with desirability value of 0.852 and low prediction errors. The optimized formulation showed good % drug entrapment efficiency (79.56 ± 2.34%), nanometer size (56.68 ± 1.2 nm), monodisperse nature (PDI = 0.176 ± 0.2), spherical morphology and good drug-excipient compatibility. The raloxifene hydrochloride loaded lipid nanocapsule hydrogel showed shear thinning properties, sustained drug delivery, dermal compatibility and significantly higher permeability (2-fold), retention (3.37) for raloxifene hydrochloride compared to the control. The present study showed a successful development of raloxifene hydrochloride loaded lipid nanocapsule hydrogel with improved skin permeation, retention, and good topical compatibility. This formulation may overcome the challenges associated with raloxifene hydrochloride oral delivery including low bioavailability.