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Preparation and Characterization of Liposome Containing Minoxidil and Rosemary Essential Oil



Minoxidil and Rosemary essential oil have been used for several years to stimulate hair growth. Therefore, co-administration of both Minoxidil and Rosemary essential oil could enhance hair growth. The chemical/biological characteristics of liposomes, which encapsulate both hydrophobic and hydrophilic drugs, can be utilized to encapsulate the herbal and chemical drug concoction concomitantly. A thin-film hydration method was used to prepare the liposomes. The entrapment efficacy of the liposomes was determined for Minoxidil and Rosemary essential oil using UV spectrophotometry and hydrodistillation; as dictated in the European pharmacopeia. Furthermore, a dynamic light scattering (DLS) analysis was conducted to determine the particle size and zeta potential of the prepared liposome. In addition, the storage stability of the liposome was checked after 60 days. The results showed that co-encapsulation of Minoxidil and Rosemary essential oil increased the encapsulation efficacy of Minoxidil while the entrapment efficacy of essential oil was not significantly influenced. In addition, according to the DLS results, the particle size and zeta potential of prepared liposomes didn't change significantly during 60 days of storage.
Preparaon and Characterizaon of Liposome Containing Minoxidil and
Rosemary Essenal Oil
Gita Kiaee1*, Hamid Akbari Javar1, Bita Kiaee2 and Shadi Kiaei3
1Tehran University of Medical Sciences, Tehran, Iran
2Islamic Azad University of Medical Science, Tehran, Iran
3Portland State University, USA
*Corresponding author: Gita Kiaee, Doctor of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Tel: 98218889 6692; E-
Received date: July 2, 2016; Accepted date: Aug 3, 2016; Published date: Aug 10, 2016
Copyright: © 2016 Kiaee G, et al. This is an open-access arcle distributed under the terms of the Creave Commons Aribuon License,
which permits unrestricted use, distribuon, and reproducon in any medium, provided the original author and source are credited.
Citaon: Kiaee G, Javar HA, Kiaee B, et al. Preparaon and Characterizaon of Liposome Containing Minoxidil and Rosemary Essenal Oil. J In
Silico In Vitro Pharmacol. 2016, 2:3.
Minoxidil and Rosemary essenal oil have been used for
several years to smulate hair growth. Therefore, co-
administraon of both Minoxidil and Rosemary essenal
oil could enhance hair growth. The chemical/biological
characteriscs of liposomes, which encapsulate both
hydrophobic and hydrophilic drugs, can be ulized to
encapsulate the herbal and chemical drug concocon
concomitantly. A thin-lm hydraon method was used to
prepare the liposomes. The entrapment ecacy of the
liposomes was determined for Minoxidil and Rosemary
essenal oil using UV spectrophotometry and
hydrodisllaon; as dictated in the European
pharmacopeia. Furthermore, a dynamic light scaering
(DLS) analysis was conducted to determine the parcle
size and zeta potenal of the prepared liposome. In
addion, the storage stability of the liposome was
checked aer 60 days. The results showed that co-
encapsulaon of Minoxidil and Rosemary essenal oil
increased the encapsulaon ecacy of Minoxidil while
the entrapment ecacy of essenal oil was not
signicantly inuenced. In addion, according to the DLS
results, the parcle size and zeta potenal of prepared
liposomes didn’t change signicantly during 60 days of
Liposomes; Hydrodisllaon; Spectrophotometry; Co-
Minoxidil and Rosemary essenal oil have been known for
their hair growth smulatory properes for several years
(Arcle 1999) [1,2] and there are several explanaons that
aribute to the Minoxidil mechanism of acon [3]. One of the
biochemical acons of Minoxidil for hair growth is its
smulatory eect on prostaglandin and Vascular endothelial
growth factor (VEGF) synthesis [4]. However, a limitaon to the
applicaon of Minoxidil is its poor skin penetraon ability and
water solubility [5]. In order to enhance Minoxidil’s
penetraon and solubility it has to be formulated in an ethanol
based soluon [5] which has been known to cause dermas
irritaon, pruritus, erythema, scaling and dryness of skin [6]. In
addion, Terpene compounds such as cineol, limonene, and
Nerolidol have been observed to improve the penetraon of
Minoxidil in the skin [7]. These Terpene compounds, especially
cineol constute the major fracon of Rosemary essenal oil
[8-10]. Therefore, co-administraon of Minoxidil and
Rosemary essenal oil can lead to the high potency for a hair
growth formulaon.
The advents of novel drug delivery system provide the
appropriate means to encapsulate both hydrophilic and
hydrophobic compounds [11]. Liposomes have capability of
increasing the concentraon of topically applied drugs in the
dermis while reducing the unfavourable risk by restricng the
absorbance of systemic drug [12]. Moreover, the similarity of
lipid composion of liposomes and membranes of intercellular
lamellae and keranocytes render the improvement in drug
release properes and skin compability [13]. Therefore,
liposomes appear to be an appropriate vehicle to co-
encapsulate Minoxidil and the Rosemary essenal oil [14].
Furthermore, previous studies of liposomal encapsulaon of
Minoxidil has led to the higher concentraon of drugs in the
pilosebace units in comparison to convenonal Minoxidil
formulaons [15]. In addion, the organic solvent deleon of
convenonal formulaons reduces the adverse side eects of
long term applicaon. Moreover, liposomal encapsulaon of
Rosemary essenal oil could protect the essenal oil against
degradaon factors such as pH and light, and increase its
stability [16].
Research Article
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Vol.2 No.3:10
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Therefore, the aim of this study is to prepare liposomes
containing Minoxidil and rosemary essenal oil that presented
acceptable physicochemical properes.
Materials and Methods
The Rosemary essenal oil was purchased from Barij
essence company and the other consumed substances were
purchased from Merck Company.
Liposome preparaon
Liposomes were prepared by a thin-lm hydraon method
as reported in the literature accurately weighed quanes of
the Egg Phosphadyl choline (EPHC) and Cholesterol (CHOL)
with the molar rao of 7:3 were dissolved in methanol:
Chloroform (1:3) mixture. The soluon was placed in a rotary
evaporator (Rotavapor R 200/205, Buchi) at 55°C unl a thin
lipid lm on the wall of a round-boomed ask was obtained.
The resulng lipid lm was kept under a vacuum overnight in
order to eliminate traces of organic solvents. The lipid lm was
then hydrated with 10 mL of the aqueous soluon described in
(Table 1) for one hour. Aerwards the homogenous
suspension of the liposome was spun in the centrifuge for 45
minute at 15000 rpm. Following the separaon of the
supernatant, the sediment was rehydrated with dislled water
and it was sonicated for 10 min by using an ultrasound bath
(Transonic 460 H, Singen), and nally the liposome mixture
was extruded with a 400 nm lter.
Table 1: Content of aqueous soluon for hydrang a thin-lm
n 1
n 2
n 3
n 4
- 1 mg/ml - 1 mg/ml
- - 300 µl 300 µl
Determinaon of Minoxidil-entrapment
The supernatant of centrifuged suspension containing
liposome were analyzed at 285 nm spectrophotometrically.
The percent drug entrapment for the prepared liposome was
calculated by using equaon (1).
(Total drug added – non entrapped drug/Total drug added) ×
100 (1)
Determinaon of Rosemary essenal oil-
entrapment ecacy
The quanty of entrapped essenal oil in the liposome was
determined via a method introduced in the European
pharmacopeia [17]. The method was carried out by means of
steam disllaon by placing the prepared liposomal soluon in
the ask described below and heat it for 30 min (Figure 1).
Aer 30 min, heang was stopped, and following 10 min of
cooling a room temperature the volume of the essenal oil
was read o. The drug entrapment percentage was calculated
using equaon (2).
(The volume of essenal oil in the tubed aer 30 minutes of
heang/Total volume of added essenal oil) × 100 (2)
Figure 1: Hydro disllaon method: Clevenger type
Size and zeta potenal
The vesicle size and zeta potenal analysis of the liposomes
were carried out by using a Malvern Zetasizer 2000 HS
(Malvern instrument limited, Malvern, UK, NIPER, SAS Nagar,
Storage stability studies
In order to determine the physical stability of the liposomes,
size of the parcle and polydispersity index (PDI) were
measured by Malvern Zetasizer. The vesicles were stored at
4°C for up to 2 months under light protecon [18]. In
predetermined me intervals, vesicles were characterized for
their vesicle size and PDI.
Results and Discussion
The inuence of rosemary essenal oil on
Minoxidil encapsulaon ecacy
The Minoxidil encapsulaon ecacy (EE) with and without
the essenal oil was 73% and 64% respecvely. Based on our
results, the liposome formulaon containing essenal oil
represented larger EE% of Minoxidil which was accompanied
by increase in the parcle size and zeta potenal of the
vesicles. The high zeta potenal frequently led to an increase
in the repulsion forces of the bilayer structure of the vesicles
Journal of In Silico & In Vitro Pharmacology
Vol.2 No.3:10
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which consequently increased the size of the liposomes.
Minoxidil, being parally hydrophobic, was expected to be
localized in the membrane compartment of lipid vesicles [13].
In Baranl et al. [10] study it was shown that Terpen compounds
such as cineol increased the entrapment ecacy of
hydrophobic drugs [10], thus the increase in EE could be
related to Terpen compound of essenal oil.
The inuence of Minoxidil on Rosemary
essenal oil encapsulaon ecacy
The essenal oil encapsulaon ecacy with and without
Minoxidil was 50% and 55% respecvely. There was no
signicant change to the encapsulaon ecacy of Rosemary
essenal oil accompanied with Minoxidil.
Size and Zeta potenal of liposomes
Zeta potenal and parcle size of the formulated vesicles
aer probe sonicaon is presented in Table 2. The results
showed that the average size of liposomes containing
Minoxidil was 169 nm with a PDI of 0.261, while the average
size of the liposomes containing Minoxidil and essenal oil was
183 nm with a PDI of 0.174. In cases of vesicles containing
solely essenal oil, the vesicle size was 187 nm with a PDI of
0.105. The parcle size of free-drug liposomes was 118 nm.
The increasing of parcle size of liposomes containing Terpene
was observed. These ndings are in agreement with previous
study [10]. The PDI of the invesgated formulaons was below
0.3, which indicates the homogeneity of the prepared
liposomes [19]. Regarding the zeta potenal measurements,
all liposomal dispersions had a negave surface charge
indicang that the formulaons were more stable and
homogeneous in distribuon. Moreover, liposomes containing
Terpene are more negave than convenonal liposomes.
These negave charge values of the obtained liposomes are
aributed to the presence of ethanol [20].
Table 2: Size and Zeta potenal of Formulaon (1): Liposome
without drugs; Formulaon (2): Minoxidil loaded liposome;
Formulaon (3): Rosemary essenal oil loaded liposome;
Formulaon (4): Minoxidil and Rosemary essenal oil loaded
liposome formulaon.
Particle size Zeta potential
Formulation 1 118 -18.8
Formulation 2 169 -34
Formulation 3 187 -37.5
Formulation 4 183 -37
Stability studies
The physical stability of the four liposome formulaons
which were stored at 4°C for 60 days presented in Figures 2
and 3. The stability results showed minimal changes of parcle
size and PDI of the invesgated liposomes. The parcle size
and the PDI of liposomal dispersions had slightly increased
aer 60 days of storage. These results showed that the co-
existence of the Minoxidil and Rosemary essenal oil in the
vesicular formulaons did not aect the vesicle’s stability
during me.
Figure 2: Size of liposome parcle in 60 days of storage for
Formulaon (1): Liposome without drugs; Formulaon (2):
Minoxidil loaded liposome; Formulaon (3): Rosemary
essenal oil loaded liposome; Formulaon (4): Minoxidil
and Rosemary essenal oil loaded liposome formulaon.
Figure 3: Zeta potenal of liposome parcle in 60 days of
storage for Formulaon (1): Liposome without drugs;
Formulaon (2): Minoxidil loaded liposome; Formulaon
(3): Rosemary essenal oil loaded liposome; Formulaon
(4): Minoxidil and Rosemary essenal oil loaded liposome
Minoxidil and Rosemary essenal oil successfully entrapped
in the liposome with appropriate size and entrapment ecacy
which possible its consumpon as the future hair growth
smulator formulaon. The stability of formulaon in terms of
size and zeta potenal remained appropriate during 60 days of
Journal of In Silico & In Vitro Pharmacology
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... Симбиоз компонентов также показал стабильность липосомы во времени, подтверждая возможность ее использования в косметических продуктах. [9] Таким образом, использование миноксидила вместе с эфирным маслом, значительно повышает вероятность его эффективной инкапсуляции в липосому, а само использование липосом в косметическом продукте для волос гарантирует транспортировку необходимого количества полезных компонентов к коже головы и корням волос. Данный симбиоз приводит к значительному снижению последствий от воздействия неблагоприятной окружающей среды, а также предупредит дальнейшие повторные процессы, дополнительно защищая и напитывая волосы и луковицы волос. ...
Phytomedicines have been widely implemented throughout the world for centuries and recognized by scientific committees and patients for their better therapeutic value, with fewer adverse effects offered by herbal medicines compared with modern drugs. The enhancement of phytotherapeutics demands a scientific approach in delivering the biological constituent efficiently, in a sustained manner to achieve patient satisfaction and avoid repeated administration. Incorporation of phytomedicines into nanotechnology is an innovative approach to magnifying the solubility, absorption rate, and permeation membrane of phytomedicine, which possess the high bioavailability and therapeutic potential of these medicinal plants. Therefore, this chapter reviews numerous investigations regarding the pharmacological activity of phytomedicine, the main factors that limit the therapeutic potential of phytomedicine, and the incorporation of phytomedicine into several nanocarriers. Hence, the overall discussion has revealed the potential of novel drug delivery systems in intensifying the bioavailability and efficacy of the pharmacological activity of phytomedicine. This finding depicts the several in vivo assays of phytomedicine-loaded nanocarriers that have been discussed throughout this chapter.
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Abstract Coriander (Coriandrum sativum L.), is an annual herb in the Apiaceae family which disperses in Mediterranean andMiddle Eastern regions. The Coriander essential oil has been used in food products, perfumes, cosmetics and pharmaceutical industries for its flavor and odor. In Iran, fruits of Coriander used in pickle, curry powders, sausages, cakes, pastries, biscuits and buns. The aim of this study was to investigate microwave radiation effects on quality, quantity and antimicrobial activity of essential oil of Coriander fruits. The essential oils were obtained from the Coriander fruits by hydrodistillation (HD) andMicrowave-assisted hydrodistillation (MAHD) then, the oils were analyzed by GC and GC-MS. Antimicrobial activities of essential oils were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans by microdilution method. The results indicated that the HD and MAHD essential oils (EO) were dominated by monoterpenoids such as linalool, geranyl acetate and γ- terpinene. The major compound in both EO was linalool which its amount in HD andMAHD was 63 %and 66 %, respectively. The total amount of monoterpenes hydrocarbons in HD EO differ significantly with the amount in MAHD EO (12.56 % compare to 1.82 %). HD EO showed greater activity against Staphylococcus aureus and Candida albicans than MAHD EO. Moreover, their activities against Ecoli and P. aeruginosa were the same with Minimum Inhibitory Concentration (MIC) 0.781 and 6.25 μL mL−1, respectively. By using MAHD method, it was superior in terms of saving energy and extraction time, although the oil yield and total composition decrease by using this method.
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We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.
A critical analysis of (trans) dermal delivery of substances encapsulated within liposomes and niosomes is presented. Topical liposomes or niosomes may serve as solubilization matrix, as a local depot for sustained release of dermally active compounds, as penetration enhancers, or as rate-limiting membrane barrier for the modulation of systemic absorption of drugs. The mechanism(s) of vesicle-skin interaction and drug delivery are being extensively investigated using radioactive- or fluorescence-labeled marker molecules and drugs, and various electron and (laser) light microscopic visualization techniques, and different models describing the interaction with and fate of vesicles in the skin have been proposed. With the current experimental data base on hand, most investigators agree that direct contact between vesicles and skin is essential for efficient delivery, although phospholipids per se apparently do not penetrate into deeper skin layers. Investigators have mostly focused on dermal corticosteroid liposome products. However, localized effects of liposome-associated proteins such as superoxide dismutase, tissue growth factors and interferons appear also to be enhanced. The delivery of liposome-encapsulated proteins and enzymes into deeper skin layers has been reported, although the mechanism of delivery remains to be elucidated. An objective assessment of the performance of topical liposome formulations vs. conventional dosage forms is frequently obscured by investigators comparing equal concentrations, rather than equivalent thermodynamic activities of their respective formulations. We conclude that liposomes and niosomes may become a useful dosage form for a variety of dermally active compounds, specifically due to their ability to modulate drug transfer and serve as nontoxic penetration enhancers.
Over the past several years, great advances have been made on development of novel drug delivery systems (NDDS) for plant actives and extracts. The variety of novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported using bioactive and plant extracts. The novel formulations are reported to have remarkable advantages over conventional formulations of plant actives and extracts which include enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation. The present review highlights the current status of the development of novel herbal formulations and summarizes their method of preparation, type of active ingredients, size, entrapment efficiency, route of administration, biological activity and applications of novel formulations.
In the past decade, liposomal formulations have been extensively employed to enhance the efficiency of drug delivery via several routes of administration. In a number of instances, liposomal drug formulations have been shown to be markedly superior to conventional dosage forms, especially for intravenous and topical modes of administration of drugs. The major advantages of topical liposomal drug formulations accrue from their demonstrated ability: (i) to reduce serious side effects and incompatibilities that may arise from undesirably high systemic absorption of drug; (ii) to enhance significantly the accumulation of drug at the site of administration as a result of the high substantivity of liposomes with biological membranes; and (iii) to readily incorporate a wide variety of hydrophilic and hydrophobic drugs. Liposomes are also non-toxic, biodegradable and are readily prepared on a large scale. This paper presents a review of topically applied liposomal formulations with emphasis on the evaluation of liposomal systems in a wide variety of animal models and human skin using both in-vivo and in-vitro techniques. The mechanism by which liposomes facilitate deposition of drugs into the skin and potential applications of topically applied liposomes are discussed. Peer Reviewed
The aim of this work was to evaluate the ability of a few different penetration enhancers to produce elastic vesicles with soy lecithin and the influence of the obtained vesicles on in vitro (trans)dermal delivery of minoxidil. To this purpose, so-called Penetration Enhancer-containing Vesicles (PEVs) were prepared as dehydrated-rehydrated vesicles by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy)ethanol (Transcutol), capryl-caproyl macrogol 8-glyceride (Labrasol), and cineole. Soy lecithin liposomes, without penetration enhancers, were used as control. Prepared formulations were characterized in terms of size distribution, morphology, zeta potential, and vesicle deformability. The influence of PEVs on (trans)dermal delivery of minoxidil was studied by in vitro diffusion experiments through newborn pig skin in comparison with traditional liposomes and ethanolic solutions of the drug also containing each penetration enhancer. A skin pre-treatment study using empty PEVs and conventional liposomes was also carried out. Results showed that all the used penetration enhancers were able to give more deformable vesicles than conventional liposomes with a good drug entrapment efficiency and stability. In vitro skin penetration data showed that PEVs were able to give a statistically significant improvement of minoxidil deposition in the skin in comparison with classic liposomes and penetration enhancer-containing drug ethanolic solutions without any transdermal delivery. Moreover, the most deformable PEVs, prepared with Labrasol and cineole, were also able to deliver to the skin a higher total amount of minoxidil than the PE alcoholic solutions thus suggesting that minoxidil delivery to the skin was strictly correlated to vesicle deformability, and therefore to vesicle composition.
Niosomes have been reported as a possible approach to improve the low skin penetration and bioavailability characteristics shown by conventional topical vehicle for minoxidil. Niosomes formed from polyoxyethylene alkyl ethers (Brij) or sorbitan monoesters (Span) with cholesterol molar ratios of 0, 1 and 1.5 were prepared with varying drug amount 20-50mg using thin film-hydration method. The prepared systems were characterized for entrapment efficiency, particle size, zeta potential and stability. Skin permeation studies were performed using static vertical diffusion Franz cells and hairless mouse skin treated with either niosomes, control minoxidil solution (propylene glycol-water-ethanol at 20:30:50, v/v/v) or a leading topical minoxidil commercial formulation (Minoxyl). The results showed that the type of surfactant, cholesterol and incorporated amount of drug altered the entrapment efficiency of niosomes. Higher entrapment efficiency was obtained with the niosomes prepared from Span 60 and cholesterol at 1:1 molar ratio using 25mg drug. Niosomal formulations have shown a fairly high retention of minoxidil inside the vesicles (80%) at refrigerated temperature up to a period of 3 months. It was observed that both dialyzed and non-dialyzed niosomal formulations (1.03+/-0.18 to 19.41+/-4.04%) enhanced the percentage of dose accumulated in the skin compared to commercial and control formulations (0.11+/-0.03 to 0.48+/-0.17%) except dialyzed Span 60 niosomes. The greatest skin accumulation was always obtained with non-dialyzed vesicular formulations. Our results suggest that these niosomal formulations could constitute a promising approach for the topical delivery of minoxidil in hair loss treatment.