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Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across Porcine Skin and Possible Interaction with Fish Oil Fatty Acids

Zulfakar MH, Chan LM, Rehman K, Wai LK, Heard CM

AAPS PharmSciTech, 2018 Apr;19(3):1116-1123.
PMID: 29181705 DOI: 10.1208/s12249-017-0923-x

Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle, CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel, oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear skin was then evaluated. Furthermore, the effects of the omega-3 fatty eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from fish oil on skin permeation were investigated by means of nuclear magnetic resonance (NMR) and computerised molecular modelling docking experiments. The highest drug permeation was achieved with the bigel formulation that proved to be the most effective vehicle in delivering CoQ10 across the skin membrane due to a combination of its adhesive, viscous and lipophilic properties. Furthermore, the interactions between CoQ10 and fatty acids revealed by NMR and molecular modelling experiments likely accounted for skin permeability of CoQ10. NMR data showed dose-dependent changes in proton chemical shifts in EPA and DHA. Molecular modelling revealed complex formation and large binding energies between fatty acids and CoQ10. This study advances the knowledge about bigels as drug delivery vehicles and highlights the use of NMR and molecular docking studies for the prediction of the influence of drug-excipient relationships at the molecular level.

Matched MeSH terms: Skin/metabolism
Sea cucumber (Stichopus hermanii) based hydrogel to treat burn wounds in rats

Zohdi RM, Zakaria ZA, Yusof N, Mustapha NM, Abdullah MN

J Biomed Mater Res B Appl Biomater, 2011 Jul;98(1):30-7.
PMID: 21504052 DOI: 10.1002/jbm.b.31828

Malaysian sea cucumber was incorporated into hydrogel formulation by using electron beam irradiation technique and was introduced as novel cross-linked Gamat Hydrogel dressing. This study investigated whether Gamat Hydrogel enhanced repair of deep partial skin thickness burn wound in rats and its possible mechanism. Wounds were treated with either Gamat Hydrogel, control hydrogel, OpSite® film dressing or left untreated. Skin samples were taken at 7, 14, 21, and 28 days post burn for histological and molecular evaluations. Gamat Hydrogel markedly enhanced wound contraction and improved histological reorganization of the regenerating tissue. Furthermore, the dressing modulated the inflammatory responses, stimulated the activation and proliferation of fibroblasts, and enhanced rapid production of collagen fiber network with a consequently shorter healing time. The level of proinflammatory cytokines; IL-1α, IL-1β, and IL-6, were significantly reduced in Gamat Hydrogel treated wounds compared with other groups as assessed by reverse transcription-polymerase chain reaction (RT-PCR). In summary, our results showed that Gamat Hydrogel promoted burn wound repair via a complex mechanism involving stimulation of tissue regeneration and regulation of pro-inflammatory cytokines. The resultant wound healing effects were attributed to the synergistic effect of the hydrogel matrix and incorporated sea cucumber.

Matched MeSH terms: Skin/metabolism
Concentration-dependent effect of platelet-rich plasma on keratinocyte and fibroblast wound healing

Xian LJ, Chowdhury SR, Bin Saim A, Idrus RB

Cytotherapy, 2015 Mar;17(3):293-300.
PMID: 25456581 DOI: 10.1016/j.jcyt.2014.10.005

Platelet-rich plasma (PRP) has been found to contain a high concentration of growth factors that are present during the process of healing. Studies conducted found that application of PRP accelerates wound healing. In this study, we characterized the skin cell suspension harvested using the co-isolation technique and evaluated the effects of PRP (10% and 20%, v/v) on co-cultured keratinocytes and fibroblasts in terms of wound healing.

Matched MeSH terms: Skin/metabolism
Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery

Wong TW

J Control Release, 2014 Nov 10;193:257-69.
PMID: 24801250 DOI: 10.1016/j.jconrel.2014.04.045

Transdermal drug delivery is hindered by the barrier property of the stratum corneum. It limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500Da and melting point of less than 200°C. Active methods such as iontophoresis, electroporation, sonophoresis, magnetophoresis and laser techniques have been investigated for the past decades on their ability, mechanisms and limitations in modifying the skin microenvironment to promote drug diffusion and partition. Microwave, an electromagnetic wave characterized by frequencies range between 300MHz and 300GHz, has recently been reported as the potential skin permeation enhancer. Microwave has received a widespread application in food, engineering and medical sectors. Its potential use to facilitate transdermal drug transport is still in its infancy stage of evaluation. This review provides an overview and update on active methods utilizing electrical, magnetic, photomechanical and cavitational waves to overcome the skin barrier for transdermal drug administration with insights into mechanisms and future perspectives of the latest microwave technique described.

Matched MeSH terms: Skin/metabolism
Physicochemical modulation of skin barrier by microwave for transdermal drug delivery

Wong TW, Nor Khaizan A

Pharm Res, 2013 Jan;30(1):90-103.
PMID: 22890987 DOI: 10.1007/s11095-012-0852-z

PURPOSE: To investigate mechanism of microwave enhancing drug permeation transdermally through its action on skin.
METHODS: Hydrophilic pectin-sulphanilamide films, with or without oleic acid (OA), were subjected to drug release and skin permeation studies. The skins were untreated or microwave-treated, and characterized by infrared spectroscopy, Raman spectroscopy, thermal, electron microscopy and histology techniques.
RESULTS: Skin treatment by microwave at 2450 MHz for 5 min promoted drug permeation from OA-free film without incurring skin damage. Skin treatment by microwave followed by film loaded with drug and OA resulted in permeation of all drug molecules that were released from film. Microwave exerted spacing of lipid architecture of stratum corneum into structureless domains which was unattainable by OA. It allowed OA to permeate stratum corneum and accumulate in dermis at a greater ease, and synergistically inducing lipid/keratin fluidization at hydrophobic C-H and hydrophilic O-H, N-H, C-O, C=O, C-N regimes of skin, and promoting drug permeation.
CONCLUSION: The microwave technology is evidently feasible for use in promotion of drug permeation across the skin barrier. It represents a new approach in transdermal drug delivery.

Matched MeSH terms: Skin/metabolism*
Transcriptome analysis in the skin of Carassius auratus challenged with Aeromonas hydrophila

Wang R, Hu X, Lü A, Liu R, Sun J, Sung YY, et al.

Fish Shellfish Immunol, 2019 Nov;94:510-516.
PMID: 31541778 DOI: 10.1016/j.fsi.2019.09.039

Skin plays an important role in the innate immune responses of fish, particularly towards bacterial infection. To understand the molecular mechanism of mucosal immunity of fish during bacterial challenge, a de novo transcriptome assembly of crucian carp Carassius auratus skin upon Aeromonas hydrophila infection was performed, the latter with Illumina Hiseq 2000 platform. A total of 118111 unigenes were generated and of these, 9693 and 8580 genes were differentially expressed at 6 and 12 h post-infection, respectively. The validity of the transcriptome results of eleven representative genes was verified by quantitative real-time PCR (qRT-PCR) analysis. A comparison with the transcriptome profiling of zebrafish skin to A. hydrophila with regards to the mucosal immune responses revealed similarities in the complement system, chemokines, heat shock proteins and the acute-phase response. GO and KEGG enrichment pathway analyses displayed the significant immune responses included TLR, MAPK, JAK-STAT, phagosome and three infection-related pathways (ie., Salmonella, Vibrio cholerae and pathogenic Escherichia coli) in skin. To our knowledge, this study is the first to describe the transcriptome analysis of C. auratus skin during A. hydrophila infection. The outcome of this study contributed to the understanding of the mucosal defense mechanisms in cyprinid species.

Matched MeSH terms: Skin/metabolism*
Characterization and functional analysis of slc7a11 gene, involved in skin color differentiation in the red tilapia

Wang LM, Bu HY, Song FB, Zhu WB, Fu JJ, Dong ZJ

Comp Biochem Physiol A Mol Integr Physiol, 2019 10;236:110529.
PMID: 31310814 DOI: 10.1016/j.cbpa.2019.110529

Red tilapia has become more popular for aquaculture production in China in recent years. However, the pigmentation differentiation that has resulted from the process of genetic breeding and skin color variation during the overwintering period are the main problems limiting the development of commercial culture. The genetic basis of skin color differentiation is still not understood. Solute carrier family 7 member 11 (slc7a11) has been identified to be a critical genetic regulator of pheomelanin synthesis in the skin of mammals. However, little information is available about its molecular characteristics, expression, location and function in skin color differentiation of fish. In this study, three complete cDNA sequences (2159 bp, 2190 bp and 2249 bp) of slc7a11 were successfully isolated from Malaysian red tilapia, encoding polypeptides of 492, 525 and 492 amino acids respectively. Quantitative real-time PCR demonstrated that slc7a11 mRNA expression is high in the ventral skin of PR (pink with scattered red spots) fish. Immunofluorescence analysis revealed that xCT (the protein encoded by slc7a11) was concentrated mainly in the cytoplasm and nucleus of both the dorsal and ventral skin cells of fish. After RNA interference of slc7a11, slc7a11 and cbs mRNA expressions decreased, but the tyr mRNA expression increased in the skin of fish. Results suggest that slc7a11 plays an important role in skin color formation and differentiation of red tilapia through the melanogenesis pathway.

Matched MeSH terms: Skin/metabolism
Influence of omega fatty acids on skin permeation of a coenzyme Q10 nanoemulsion cream formulation: characterization, in silico and ex vivo determination

Tou KAS, Rehman K, Ishak WMW, Zulfakar MH

Drug Dev Ind Pharm, 2019 Sep;45(9):1451-1458.
PMID: 31216907 DOI: 10.1080/03639045.2019.1628042

Objective: The aim of this study was to develop a coenzyme Q10 nanoemulsion cream, characterize and to determine the influence of omega fatty acids on the delivery of coenzyme Q10 across model skin membrane via ex vivo and in silico techniques. Methods: Coenzyme Q10 nanoemulsion creams were prepared using natural edible oils such as linseed, evening primrose, and olive oil. Their mechanical features and ability to deliver CoQ10 across rat skin were characterized. Computational docking analysis was performed for in silico evaluation of CoQ10 and omega fatty acid interactions. Results: Linseed, evening primrose, and olive oils each produced nano-sized emulsion creams (343.93-409.86 nm) and exhibited excellent rheological features. The computerized docking studies showed favorable interactions between CoQ10 and omega fatty acids that could improve skin permeation. The three edible-oil nanoemulsion creams displayed higher ex vivo skin permeation and drug flux compared to the liquid-paraffin control cream. The linseed oil formulation displayed the highest skin permeation (3.97 ± 0.91 mg/cm2) and drug flux (0.19 ± 0.05 mg/cm2/h). Conclusion: CoQ10 loaded-linseed oil nanoemulsion cream displayed the highest skin permeation. The highest permeation showed by linseed oil nanoemulsion cream may be due to the presence of omega-3, -6, and -9 fatty acids which might serve as permeation enhancers. This indicated that the edible oil nanoemulsion creams have potential as drug vehicles that enhance CoQ10 delivery across skin.

Matched MeSH terms: Skin/metabolism
The effect of topical extract of Momordica charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with diabetes induced by streptozotocin

Teoh SL, Latiff AA, Das S

Clin Exp Dermatol, 2009 Oct;34(7):815-22.
PMID: 19508570 DOI: 10.1111/j.1365-2230.2008.03117.x

Momordica charantia (MC; bitter gourd) is a traditional herb commonly used for its antidiabetic, antioxidant, contraceptive and antibacterial properties. It is also used for the rapid healing of wounds.

Matched MeSH terms: Skin/metabolism
Effect of non-phospholipid-based cationic and phospholipid-based anionic nanosized emulsions on skin retention and anti-inflammatory activity of celecoxib

Tamilvanan S, Baskar R

Pharm Dev Technol, 2013 Jul-Aug;18(4):761-71.
PMID: 23668371 DOI: 10.3109/10837450.2011.586038

Celecoxib (CXB, 0.2 g)-loaded anionic and cationic nanosized emulsions were prepared by a well-established combined emulsification method.

Matched MeSH terms: Skin/metabolism
Fulltext The Role of Calcium in Wound Healing

Subramaniam T, Fauzi MB, Lokanathan Y, Law JX

Int J Mol Sci, 2021 Jun 17;22(12).
PMID: 34204292 DOI: 10.3390/ijms22126486

Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.

Matched MeSH terms: Skin/metabolism
Co-localization of LTBP-2 with FGF-2 in fibrotic human keloid and hypertrophic scar

Sideek MA, Teia A, Kopecki Z, Cowin AJ, Gibson MA

J Mol Histol, 2016 Feb;47(1):35-45.
PMID: 26644005 DOI: 10.1007/s10735-015-9645-0

We have recently shown that Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) has a single high-affinity binding site for fibroblast growth factor-2 (FGF-2) and that LTBP-2 blocks FGF-2 induced cell proliferation. Both proteins showed strong co-localisation within keloid skin from a single patient. In the current study, using confocal microscopy, we have investigated the distribution of the two proteins in normal and fibrotic skin samples including normal scar tissue, hypertrophic scars and keloids from multiple patients. Consistently, little staining for either protein was detected in normal adult skin and normal scar samples but extensive co-localisation of the two proteins was observed in multiple examples of hypertrophic scars and keloids. LTBP-2 and FGF-2 were co-localised to fine fibrous elements within the extracellular matrix identified as elastic fibres by immunostaining with anti-fibrillin-1 and anti-elastin antibodies. Furthermore, qPCR analysis of RNA samples from multiple patients confirmed dramatically increased expression of LTBP-2 and FGF-2, similar TGF-beta 1, in hypertrophic scar compared to normal skin and scar tissue. Overall the results suggest that elevated LTBP-2 may bind and sequester FGF-2 on elastic fibres in fibrotic tissues and modulate FGF-2's influence on the repair and healing processes.

Matched MeSH terms: Skin/metabolism*
A feasibility study: in vivo x-ray fluorescence of iron using 109Cd

Shukri A, Green S, Bradley DA

Appl Radiat Isot, 1995 6 1;46(6-7):625.
PMID: 7633384
Matched MeSH terms: Skin/metabolism
Fabrication and characterization of matrix type transdermal patches loaded with tizanidine hydrochloride: potential sustained release delivery system

Shahid N, Siddique MI, Razzaq Z, Katas H, Waqas MK, Rahman KU

Drug Dev Ind Pharm, 2018 Dec;44(12):2061-2070.
PMID: 30081679 DOI: 10.1080/03639045.2018.1509081

OBJECTIVE: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.
SIGNIFICANCE: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.
METHODS: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.
RESULTS: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.
CONCLUSIONS: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.

Matched MeSH terms: Skin/metabolism
Effect of limonene on permeation enhancement of ketoprofen in palm oil esters nanoemulsion

Sakeena MH, Elrashid SM, Muthanna FA, Ghassan ZA, Kanakal MM, Laila L, et al.

J Oleo Sci, 2010;59(7):395-400.
PMID: 20513974

This study sets out to investigate the in vitro permeation of ketoprofen from the formulated nanoemulsions through excised rat skin. In vitro permeation of ketoprofen nanoemulsion through rat skin was evaluated in Franz diffusion cells and compared with marketed product (Fastum gel). Limonene which has been reported to be a good enhancer for ketoprofen was selected. Moreover the effects of limonene which was added to the nanoemulsion formulations at levels of 1%, 2%, 3% and on rat skin permeation of ketoprofen were also evaluated. The selected optimized formulation was further studied for skin irritation. Utilization of limonene as a penetration enhancer increased the permeation of ketoprofen from the formulated nanoemulsion with increasing concentrations of limonene. The results obtained showed that nanoemulsion with 3% limonene produced similar and comparable skin permeation of ketoprofen with marketed formulation and the skin irritation study on rats showed the optimized formulation prepared was safe.

Matched MeSH terms: Skin/metabolism*
Expanding the applications of microneedles in dermatology

Sabri AH, Ogilvie J, Abdulhamid K, Shpadaruk V, McKenna J, Segal J, et al.

Eur J Pharm Biopharm, 2019 Jul;140:121-140.
PMID: 31059780 DOI: 10.1016/j.ejpb.2019.05.001

Since the first patent for microneedles was filed in the 1970s, research on utilising microneedles as a drug delivery system has progressed significantly. In addition to the extensive research on microneedles for improving transdermal drug delivery, there is a growing interest in using these devices to manage dermatological conditions. This review aims to provide the background on microneedles, the clinical benefits, and challenges of the device along with the potential dermatological conditions that may benefit from the application of such a drug delivery system. The first part of the review provides an outline on benefits and challenges of translating microneedle-based drug delivery systems into clinical practice. The second part of the review covers the application of microneedles in treating dermatological conditions. The efficacy of microneedles along with the limitations of such a strategy to treat diseased skin shall be addressed.

Matched MeSH terms: Skin/metabolism
Fulltext Thermodynamic stability, in-vitro permeability, and in-silico molecular modeling of the optimal Elaeis guineensis leaves extract water-in-oil nanoemulsion

Romes NB, Abdul Wahab R, Abdul Hamid M, Oyewusi HA, Huda N, Kobun R

Sci Rep, 2021 10 21;11(1):20851.
PMID: 34675286 DOI: 10.1038/s41598-021-00409-0

Nanoemulsion is a delivery system used to enhance bioavailability of plant-based compounds across the stratum corneum. Elaeis guineensis leaves are rich source of polyphenolic antioxidants, viz. gallic acid and catechin. The optimal E. guineensis leaves extract water-in-oil nanoemulsion was stable against coalescence, but it was under significant influence of Ostwald ripening over 90 days at 25 °C. The in-vitro permeability revealed a controlled and sustained release of the total phenolic compounds (TPC) of EgLE with a cumulative amount of 1935.0 ± 45.7 µgcm-2 after 8 h. The steady-state flux and permeation coefficient values were 241.9 ± 5.7 µgcm-2 h-1 and 1.15 ± 0.03 cm.h-1, respectively. The kinetic release mechanism for TPC of EgLE was best described by the Korsmeyer-Peppas model due to the highest linearity of R2 = 0.9961, indicating super case II transport mechanism. The in-silico molecular modelling predicted that the aquaporin-3 protein in the stratum corneum bonded preferably to catechin over gallic acid through hydrogen bonds due to the lowest binding energies of - 57.514 kcal/mol and - 8.553 kcal/mol, respectively. Thus, the in-silico study further verified that catechin could improve skin hydration. Therefore, the optimal nanoemulsion could be used topically as moisturizer to enhance skin hydration based on the in-silico prediction.

Matched MeSH terms: Skin/metabolism
Development and physical characterization of polymer-fish oil bigel (hydrogel/oleogel) system as a transdermal drug delivery vehicle

Rehman K, Mohd Amin MC, Zulfakar MH

J Oleo Sci, 2014;63(10):961-70.
PMID: 25252741

Polymer-Fish oil bigel (hydrogel/oleogel colloidal mixture) was developed by using fish oil and natural (sodium alginate) and synthetic (hydroxypropyl methylcellulose) polymer for pharmaceutical purposes. The bigels were closely monitored and thermal, rheological and mechanical properties were compared with the conventional hydrogels for their potential use as an effective transdermal drug delivery vehicle. Stability of the fish oil fatty acids (especially eicosapentanoic acid, EPA and docosahexanoic acid, DHA) was determined by gas chromatography and the drug content (imiquimod) was assessed with liquid chromatography. Furthermore, in vitro permeation study was conducted to determine the capability of the fish oil-bigels as transdermal drug delivery vehicle. The bigels showed pseudoplastic rheological features, with excellent mechanical properties (adhesiveness, peak stress and hardness), which indicated their excellent spreadability for application on the skin. Bigels prepared with mixture of sodium alginate and fish oil (SB1 and SB2), and the bigels prepared with the mixture of hydroxypropyl methylcellulose and fish oil (HB1-HB3) showed high cumulative permeation and drug flux compared to hydrogels. Addition of fish oil proved to be beneficial in increasing the drug permeation and the results were statistically significant (p < 0.05, one-way Anova, SPSS 20.0). Thus, it can be concluded that bigel formulations could be used as an effective topical and transdermal drug delivery vehicle for pharmaceutical purposes.

Matched MeSH terms: Skin/metabolism*
Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents

Rehman K, Tan CM, Zulfakar MH

Drug Res (Stuttg), 2014 Mar;64(3):159-65.
PMID: 24026957 DOI: 10.1055/s-0033-1355351

Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA) are one of the common treatments for inflammatory skin diseases. However, the amount of drug delivery through the skin is limited due to the stratum corneum. The purposes of this study were to investigate the ability of fish oil to act as penetration enhancer for topical keratolytic agents and to determine the suitable gelator for formulating stable fish oil oleogels. 2 types of gelling agents, beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and comparative analysis was performed using Franz diffusion cell. Stability of oleogels was determined by physical assessments at 20°C and 40°C storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were considered as better formulations in terms of drug permeation and cumulative drug release. All the results were found to be statistically significant (p<0.05, ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can prove to be beneficial in terms of permeation across the skin and stability.

Matched MeSH terms: Skin/metabolism
Probing the effects of fish oil on the delivery and inflammation-inducing potential of imiquimod

Rehman K, Aluwi MF, Rullah K, Wai LK, Mohd Amin MC, Zulfakar MH

Int J Pharm, 2015 Jul 25;490(1-2):131-41.
PMID: 26003416 DOI: 10.1016/j.ijpharm.2015.05.045

Imiquimod is a chemotherapeutic agent for many skin-associated diseases, but it has also been associated with inflammatory side effects. The aim of this study was to prevent the inflammatory effect of commercial imiquimod (Aldara(®)) by controlled release of imiquimod through a hydrogel/oleogel colloidal mixture (CA bigel) containing fish oil as an anti-inflammatory agent. Imiquimod permeability from Aldara® cream and bigel through mice skin was evaluated, and the drug content residing in the skin via the tape stripping technique was quantified. The fish oil fatty acid content in skin along with its lipophilic environment was also determined. An inflammation study was conducted using animal models, and Aldara(®) cream was found to potentially cause psoriasis-like inflammation, which could be owing to prolonged application and excessive drug permeation. Controlled release of imiquimod along with fish oil through CA bigel may have caused reduced imiquimod inflammation. NMR studies and computerized molecular modeling were also conducted to observe whether the fish oil and imiquimod formed a complex that was responsible for improving imiquimod transport and reducing its side effects. NMR spectra showed dose-dependent chemical shifts and molecular modeling revealed π-σ interaction between EPA and imiquimod, which could help reduce imiquimod inflammation.

Matched MeSH terms: Skin/metabolism*

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