Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

The aim of this study was to prepare and evaluate α-mangostin-loaded polymeric nanoparticle gel (α-MNG-PLGA) formulation to enhance α-mangostin delivery in an epidermal carcinoma. The poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed using the emulsion–diffusion–evaporation technique with a 3-level 3-factor Box–Behnken design. The NPs were characterized and evaluated for particle size distribution, zeta potential (mV), drug release, and skin permeation. The formulated PLGA NPs were converted into a preformed carbopol gel base and were further evaluated for texture analysis, the cytotoxic effect of PLGA NPs against B16-F10 melanoma cells, and in vitro radical scavenging activity. The nanoscale particles were spherical, consistent, and average in size (168.06 ± 17.02 nm), with an entrapment efficiency (EE) of 84.26 ± 8.23% and a zeta potential of −25.3 ± 7.1 mV. Their drug release percentages in phosphate-buffered solution (PBS) at pH 7.4 and pH 6.5 were 87.07 ± 6.95% and 89.50 ± 9.50%, respectively. The release of α-MNG from NPs in vitro demonstrated that the biphasic release system, namely, immediate release in the initial phase, was accompanied by sustained drug release. The texture study of the developed α-MNG-PLGA NPs gel revealed its characteristics, including viscosity, hardness, consistency, and cohesiveness. The drug flux from α-MNG-PLGA NPs gel and α-MNG gel was 79.32 ± 7.91 and 16.88 ± 7.18 µg/cm2/h in 24 h, respectively. The confocal study showed that α-MNG-PLGA NPs penetrated up to 230.02 µm deep into the skin layer compared to 15.21 µm by dye solution. MTT assay and radical scavenging potential indicated that α-MNG-PLGA NPs gel had a significant cytotoxic effect and antioxidant effect compared to α-MNG gel (p < 0.05). Thus, using the developed α-MNG-PLGA in treating skin cancer could be a promising approach.

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Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy

Polymers ◽

10.3390/polym13060923 ◽

2021 ◽

Vol 13 (6) ◽

pp. 923

Author(s):

Shadab Md ◽

Nabil A. Alhakamy ◽

Hibah M. Aldawsari ◽

Mohammad Husain ◽

Nazia Khan ◽

...

Keyword(s):

Skin Cancer ◽

Zeta Potential ◽

Skin Permeation ◽

Entrapment Efficiency ◽

Aqueous Solubility ◽

Skin Layer ◽

Vesicle Size ◽

Cytotoxicity Activities

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ±6.0 and 79.43 ± 12.43 µg/ cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.

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Nanostructured Ethosomal Gel Loaded with Arctostaphylos uva-ursi extract; In-vitro/In-vivo Evaluation as a Cosmeceutical Product

Current Drug Delivery ◽

10.2174/1567201818666210729111026 ◽

2021 ◽

Vol 18 ◽

Author(s):

Nayla Javed ◽

Shakeel Ijaz ◽

Naveed Akhtar ◽

Haji Muhammad Shoaib Khan

Keyword(s):

Zeta Potential ◽

Biological Activities ◽

Skin Permeation ◽

Radical Scavenging ◽

Reducing Power ◽

Potential Candidate ◽

Skin Rejuvenation ◽

In Vivo Evaluation

Background: Arctostaphylos uva-ursi (AUU) being rich in polyphenols and arbutin is known to have promising biological activities and can be a potential candidate as a cosmaceutical. Ethosomes encourage the formation of lamellar-shaped vesicles with improved solubility and entrapment of many drugs including plant extracts. Objective: The objective of this work was to develop an optimized nanostructured ethosomal gel formulation loaded with AUU extract and evaluated for skin rejuvenation and depigmentation. Methods: AUU extract was tested for phenolic and flavonoid content, radical scavenging potential, reducing power activity, and in-vitro SPF (sun protection factor) estimation. AUU loaded 12 formulations were prepared and characterized by SEM (scanning electron microscopy), vesicular size, zeta potential, and entrapment efficiency (%EE). The optimized formulation was subjected to non-invasive in-vivo investigations after incorporating it into the gel system and ensuring its stability and skin permeation. Results: Ethosomal vesicles were spherical in shape and Zeta size, zeta potential, PDI (polydispersity index), % EE and in-vitro skin permeation of optimized formulation (F3) were found to be 114.7nm, -18.9mV, 0.492, 97.51±0.023%, and 79.88±0.013% respectively. AUU loaded ethosomal gel formulation was stable physicochemically and exhibited non-Newtonian behavior rheologically. Moreover, it significantly reduced skin erythema, melanin as well as sebum level and improved skin hydration and elasticity. Conclusion: A stable AUU based ethosomal gel formulation could be a better vehicle for phytoextracts than conventional formulations for cosmeceutical applications such as for skin rejuvenation and depigmentation etc.

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Development and Evaluations of Transdermally Delivered Luteolin Loaded Cationic Nanoemulsion: In Vitro and Ex Vivo Evaluations

Pharmaceutics ◽

10.3390/pharmaceutics13081218 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1218

Author(s):

Mohammad A. Altamimi ◽

Afzal Hussain ◽

Sultan Alshehri ◽

Syed Sarim Imam ◽

Usamah Abdulrahman Alnemer

Keyword(s):

Drug Release ◽

Zeta Potential ◽

Transdermal Delivery ◽

Ex Vivo ◽

Skin Permeation ◽

Oral Drug ◽

In Vitro Drug Release ◽

Drug Deposition ◽

Drug Content

Introduction: Luteolin (LUT) is natural flavonoid with multiple therapeutic potentials and is explored for transdermal delivery using a nanocarrier system. LUT loaded cationic nanoemulsions (CNE1–CNE9) using bergamot oil (BO) were developed, optimized, and characterized in terms of in vitro and ex vivo parameters for improved permeation. Materials and methods: The solubility study of LUT was carried out in selected excipients, namely BO, cremophor EL (CEL as surfactant), labrasol (LAB), and oleylamine (OA as cationic charge inducer). Formulations were characterized with globular size, polydispersity index (PDI), zeta potential, pH, and thermodynamic stability studies. The optimized formulation (CNE4) was selected for comparative investigations (% transmittance as %T, morphology, chemical compatibility, drug content, in vitro % drug release, ex vivo skin permeation, and drug deposition, DD) against ANE4 (anionic nanoemulsion for comparison) and drug suspension (DS). Results: Formulations such as CNE1–CNE9 and ANE4 (except CNE6 and CNE8) were found to be stable. The optimized CNE4 based on the lowest value of globular size (112 nm), minimum PDI (0.15), and optimum zeta potential (+26 mV) was selected for comparative assessment against ANE4 and DS. The %T values of CNE1–CNE9 were found to be ˃95% and CEL content slightly improved the %T value. The spherical CNE4 was compatible with excipients and showed % total drug content in the range of 97.9–99.7%. In vitro drug release values from CNE4 and ANE4 were significantly higher than DS. Moreover, permeation flux (138.82 ± 8.4 µg/cm2·h), enhancement ratio (8.23), and DD (10.98%) were remarkably higher than DS. Thus, ex vivo parameters were relatively high as compared to DS which may be attributed to nanonization, surfactant-mediated reversible changes in skin lipid matrix, and electrostatic interaction of nanoglobules with the cellular surface. Conclusion: Transdermal delivery of LUT can be a suitable alternative to oral drug delivery for augmented skin permeation and drug deposition.

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The influence of Propylene glycol/Water and Ethanol/Water Binary Solvents on the in vitro Permeation of Garcinia mangostana L. Pericarp Extract across Shed Snakeskin

INDONESIAN JOURNAL OF PHARMACY ◽

10.22146/ijp.599 ◽

2020 ◽

pp. 187

Author(s):

Rina Kuswahyuning ◽

TN Saifullah Sulaiman ◽

Galuh Wahyu Ananingrum ◽

Rias Reno Andini

Keyword(s):

Propylene Glycol ◽

Radical Scavenging Activity ◽

Skin Permeation ◽

Radical Scavenging ◽

Binary Solvents ◽

Scavenging Activity ◽

Garcinia Mangostana ◽

Water Solvent ◽

In Vitro Skin Permeation

Garcinia mangostana pericarp (GMP) has antioxidant activity thus may be developed into a topical antioxidant formulation. This research aimed to study the topical delivery of GMP extract. Initially, some commonly used topical solvents, i.e., water and binary solvents of propylene glycol (PG)/water and ethanol/water (0; 10; 20 and 40%), were used to dissolve GMP extract and further tested on GMP extract in vitro skin permeation using shed snakeskin. The influence of solvents' effects was evaluated based on radical DPPH scavenging activity and expressed as radical scavenging activity equivalent GMP Extract (RSGMPE). The results showed that RSGMPE could be delivered into shed snakeskin. The extent of RSGMPE shed snakeskin retention was similar among water and all PG/water or ethanol/water binary solvents. RSGMPE was also found in the receptor phase from all PG/water binary solvents, whereas that from ethanol/water solvents only shown from 20% ethanol/water solvent even though all ethanol-water solvents produced significantly higher RSGMPE compared to water and PG/water binary solvents

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Cholesterol-Conjugate as a New Strategy to Improve the Cytotoxic Effect of 5-Fluorouracil on Liver Cancer: Impact of Liposomal Composition

Current Drug Delivery ◽

10.2174/1567201817666200211095452 ◽

2020 ◽

Vol 17 (10) ◽

pp. 898-910 ◽

Cited By ~ 2

Author(s):

Saleh Ayed Alanazi ◽

Gamaleldin Ibrahim Harisa ◽

Mohammad M. Badran ◽

Nazrul Haq ◽

Awwad Abdoh Radwan ◽

...

Keyword(s):

Particle Size ◽

Drug Release ◽

Zeta Potential ◽

Cytotoxic Effect ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Entrapment Efficiency ◽

Therapeutic Index ◽

Liver Malignancy

Purpose: Hepatocellular carcinoma (HCC) is a common liver malignancy, which has a low survival rate of all cancers. 5-fluorouracil (5-FU) is clinically recognized to treat HCC. However, the success of this therapy is highly limited due to rapid clearance and non- selective distribution. Cholesterol- conjugate (5-FUC) loaded liposomes proposed to facilitate the transport of 5-FUC into tumor cells via Low-Density Lipoprotein receptor (LDL receptor) that overexpressed in HCC. Thus, the aim of this study was to use 5-FUC loaded liposome as a promising strategy to combat HCC and improve the response of HCC to chemotherapy. Methods: 5-FUC and 5-FU loaded liposomes were optimized based on Cholesterol (CHO) ratio and type of phospholipid to achieve a potential effect on HCC. Liposomes were prepared by the thin-film hydration method, and evaluated in terms of particle size, polydispersity, zeta potential, Entrapment Efficiency (EE), morphology, drug release and cytotoxicity. Results: The obtained liposomes had a suitable nano-range particle size with negative zeta potential, and acceptable EE%. In vitro drug release of 5-FUC loaded liposomes showed a lower cumulative release over 24 h as compared to 5-FU loaded liposomes. 5-FUC loaded liposomes exhibited a higher in vitro cytotoxic effect as compared to the free drug and 5-FU loaded liposomes against HepG2 cell lines after 48 h via MTT assay. Conclusion: These results concluded that 5-FUC loaded liposomes could be used as an alternative tactic to increase the therapeutic index of 5-FU and pave the way for potential clinical applications.

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FORMULATION, CHARACTERIZATION AND EVALUATION OF ANTI-INFLAMMATORY AND ANTI-ANGIOGENIC ACTIVITIES OF MEMECYLAENE NANOEMULSION

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5-s.1915 ◽

2018 ◽

Vol 8 (5-s) ◽

pp. 126-131

Author(s):

ND Rekha ◽

Dattatri K. Nagesha ◽

PH Rajasree ◽

N Shruthi

Keyword(s):

Zeta Potential ◽

Biological Activities ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

In Vivo Model ◽

Particle Size Range ◽

Nitric Oxide Radical ◽

Anti Oxidant ◽

Anti Inflammatory

The present study was undertaken to formulate and evaluate the anti-inflammatory, anti-oxidant and anti-angiogenic activities of nanoemulsion of Memecylaene. Memecylaene was isolated from the leaves of Memecylon malabaricum by using various chromatographic methods. An oil-in-water (O/W) nanoemulsion of Memecylaene was formulated by sonication method using sunflower oil (oil phase), Tween 80 (Surfactant) and Ethanol (co-surfactant). The prepared nanoemulsion was characterized for its droplet size, poly dispersity index and zeta potential. Stability studies were performed and the nanoemulsions were subjected to different biological activities. The formulated nanoemulsion had a particle size range of 52.02 nm to 59.47 nm and zeta potential of -1.27 mV. The enhanced activity of Memecylaene, encapsulated in O/W emulsions is evidenced by the inhibition of phospholipase (PLA2) enzyme and H+, K+ -ATPase and thus showing anti-inflammatory and anti-secretagogues effects. The in vitro anti-oxidant activity was evaluated by DPPH radical and Nitric oxide radical scavenging activity. Further, the inhibition of the growth of neo vessels formation in the in-vivo model system of chick chorioallantoic membrane (CAM) assay, which is angiogenesis dependent, was also observed. The above findings would help in understanding the putative potential of Memecylaene-loaded nanoemulsion as a therapeutic agent. Keywords: Anti-angiogenesis, Anti-oxidant, Gastric (H+ K+), Memecylaene, Nanoemulsion, Phospholipase A2 (PLA2).

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Oleic Acid Nanovesicles of Minoxidil for Enhanced Follicular Delivery

Medicines ◽

10.3390/medicines5030103 ◽

2018 ◽

Vol 5 (3) ◽

pp. 103 ◽

Cited By ~ 9

Author(s):

Pawan Kumar ◽

Shailendra Singh ◽

Vandana Handa ◽

Himanshu Kathuria

Keyword(s):

Oleic Acid ◽

Side Effects ◽

Confocal Microscopy ◽

Drug Release ◽

Zeta Potential ◽

Skin Permeation ◽

Entrapment Efficiency ◽

Hair Follicles ◽

In Vitro Drug Release

Current topical minoxidil (MXD) formulations involve an unpleasant organic solvent which causes patient incompliance in addition to side effects in some cases. Therefore, the objective of this work was to develop an MXD formulation providing enhanced follicular delivery and reduced side effects. Oleic acid, being a safer material, was utilized to prepare the nanovesicles, which were characterized for size, entrapment efficiency, polydispersity index (PDI), zeta potential, and morphology. The nanovesicles were incorporated into the emugel Sepineo® P 600 (2% w/v) to provide better longer contact time with the scalp and improve physical stability. The formulation was evaluated for in vitro drug release, ex vivo drug permeation, and drug deposition studies. Follicular deposition of the vesicles was also evaluated using a differential tape stripping technique and elucidated using confocal microscopy. The optimum oleic acid vesicles measured particle size was 317 ± 4 nm, with high entrapment efficiency (69.08 ± 3.07%), narrow PDI (0.203 ± 0.01), and a negative zeta potential of −13.97 ± 0.451. The in vitro drug release showed the sustained release of MXD from vesicular gel. The skin permeation and deposition studies revealed superiority of the prepared MXD vesicular gel (0.2%) in terms of MXD deposition in the stratum corneum (SC) and remaining skin over MXD lotion (2%), with enhancement ratios of 3.0 and 4.0, respectively. The follicular deposition of MXD was 10-fold higher for vesicular gel than the control. Confocal microscopy also confirmed the higher absorption of rhodamine via vesicular gel into hair follicles as compared to the control. Overall, the current findings demonstrate the potential of oleic acid vesicles for effective targeted skin and follicular delivery of MXD.

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DEVELOPMENT AND OPTIMIZATION OF MANNOSYLATED NARINGENIN LOADED TRANSFERSOMES USING RESPONSE SURFACE METHODOLOGY FOR SKIN CARCINOMA

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i2.40436 ◽

2021 ◽

pp. 235-241

Author(s):

NIKITA VERMA ◽

SWARNLATA SARAF

Keyword(s):

Free Radical ◽

Zeta Potential ◽

Ex Vivo ◽

Skin Permeation ◽

Research Work ◽

Radical Scavenging ◽

Entrapment Efficiency ◽

Mannose Receptor ◽

Skin Carcinoma

Objective: The flavonoidal drug Naringenin offers a natural defense against free radical generation due to their antioxidant i.e. free radical scavenging property. The continuation of research work towards the invention of targeting the flavonoidal drug for skin carcinoma. Naringenin is a potent antioxidant, having remarkable reactive oxygen species scavenging potential and abundantly found in citrus fruits. Methods: The optimization of the formulated mannosylated naringenin-loaded transfersomes (MA-NgTfs) was performed using Box–Behnken statistical design to obtain crucial variable parameters that influence vesicular size, size distribution and surface charge. Therefore keeping both the concepts in mind our objective is to design and optimize the mannosylated naringenin loaded transfersomes (MA-NgTfs) for macropahge targeting. The Box Behnken with 3D surface response design graph was employed to optimize the formulation. Results: Phospholipids and surfactant ratio played a remarkable role to determine the mean vesicular size and the Zeta potential of the vesicles. The Zeta potential is found in the formulation having a range of-18.01±1.05 to-28.7±1.008 mV represents the good stability of the formulation. The vesicles size range was found in the range of 102.4±1.01 to 263.74±0.63 and range of Entrapment efficiency of nanovesicles was as 72.04±1.53 to 82.04±0.81. In vitro drug release study shows that mannosylated naringenin loaded transfersomes (MA-NgTfs), and marketed formulation dispersion was found 69.31 %, 62.03 %, 58.71 %, and 65.02 % respectively. Ex vivo skin permeation and deposition study shows that the marketed product and pure drug suspension optimized transfersomes through the skin of mice was of flux 6.5±3.07 and the percentage of drug retention was 0.76±1.26. The results gave us strong evidence of cellular uptake bymannose–directed transfersomes via mannose receptor-based endocytosis. Conclusion: On the basis of findings, the study revealed that the prepared formulation has characteristic potential for targeting and the concept of ligand directed nanocarrier formulation was imparts synergistic effect against UV-induced skin carcinoma.

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Allopurinol Loaded Transferosomes for the Alleviation of Symptomatic After-effects of Gout: An Account of Pharmaceutical Implications

Current Drug Therapy ◽

10.2174/1574885515666200120124214 ◽

2020 ◽

Vol 15 (4) ◽

pp. 404-419

Author(s):

Ruchi Tiwari ◽

Gaurav Tiwari ◽

Rachna Singh

Keyword(s):

Drug Release ◽

Zeta Potential ◽

Ex Vivo ◽

Release Kinetics ◽

Skin Permeation ◽

Skin Irritation ◽

In Vivo Studies ◽

Transdermal Drug Delivery System

Background: The present study assessed the transdermal potential of transferosomes loaded with allopurinol for the treatment of gout. Methods: Transferosomes of allopurinol were composed of different ratios of tween-80, soya lecithin and solvent using a thin-film hydration method. Transferosomes were characterized for Scanning Electron Microscopy (SEM), zeta potential, % entrapment efficiency (%EE), Fourier Transform Infrared Spectroscopy (FTIR), in-vitro drug release and kinetics as well as stability. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, ex vivo skin permeation study, flux, and stability. Results: SEM studies suggested that vesicles were spherical and zeta potential were in the range of -11.4 mV to -29.6 mV and %EE was 52.4- 83.87%. FTIR study revealed that there was no interaction between allopurinol and excipients during the preparation of transferosomes. The cumulative percentage of drug release from various transferosomes was ranged from 51.87 to 81.87%. A transferosomal gel of F8 formulation was prepared using dispersion method reported pseudoplastic rheological behavior, optimum pH, spreadability and maximum drug permeation i.e. 79.84% with flux 13.06 g/cm2/hr, followed zero-order release kinetics. Irritation and in-vivo studies of optimized transferosomal gel G8 on rabbits revealed better results than the standard allopurinol. Conclusion: This research suggested that allopurinol loaded transferosomal gel can be potentially used as a transdermal drug delivery system for the treatment of gout.

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Process Optimization of Curcumin-Loaded Coconut Oil and Honey Nanoemulsion for Better Skin Permeation

International Journal of Nanoscience ◽

10.1142/s0219581x20500064 ◽

2020 ◽

Vol 19 (06) ◽

pp. 2050006

Author(s):

Nur Hulwani Md Saari ◽

Lee Suan Chua ◽

Rosnani Hasham

Keyword(s):

Particle Size ◽

Radical Scavenging Activity ◽

Skin Permeation ◽

In Vitro Release ◽

Radical Scavenging ◽

Coconut Oil ◽

Bioactive Compound ◽

Polydispersity Index ◽

Independent Variables

This study was focused on the optimization of preparing a curcumin-loaded coconut oil and honey nanoemulsion using a low energy emulsifying technique. Curcumin is a bioactive compound with low bioavailability and stability. Response surface methodology (RSM) with Box Behnken design was used to optimize the base formulation based on the three independent variables such as honey (1–3%), virgin coconut oil (1.0–1.5%) and Tween 80 (5.0–9.0%) to obtain low particle size (10.11[Formula: see text]nm), polydispersity index (0.27) and turbidity (0.24–1.11) system. Subsequently, the second optimization was carried out after curcumin was loaded into the base formulation. Another three independent variables such as polyethelene glycol (0.8–1.5%), curcumin (0.01–0.1%) and honey (1.8–2.4%) were used to produce the nanorange of particle size (14.32[Formula: see text]nm), narrow polydispersity index (0.152), and high encapsulation efficiency (98.0%). The curcumin-loaded nanoemulsion was found to have high stability with only 8.5% increment in particle size after storage for three months at 4∘C and 45∘C. The radical scavenging activity of encapsulated curcumin in nanoemulsion was decreased ([Formula: see text]%) compared to free curcumin. Nanoemulsion appeared to increase in vitro release rate of curcumin by about 42%, especially for the first 2[Formula: see text]h in Franz diffusion cell using rat skin.

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