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Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of f...
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... correspondence to this author at the Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan; Tel: +92-314-2082825; Fax: +92-992-383441; E-mail: gmdogar356@gmail.com Finasteride (4-aza-3-oxosteroid) is a potent, selective and competitive inhibitor of 5-reductase isoenzyme. It was pri- marily formulated in 5 mg dose for treatment of benign pros- tate hyperplasia while presently approved and marketed for androgenetic alopecia in the dose of 1 mg as tablet [1]. It specifically blocks the conversion of testosterone to dihydro- testosterone and decreases level of dihydrotestosterone in the blood and hair-follicles ( Fig. 2) ...
Citations
... Studies are required to develop topical HS proteoglycan formula. However, some studies highlight possible vehicle or formula to induce the HS proteoglycan skin penetration such as polymersomes, vesicular nanocarriers, liposomes, nanoparticles, topical solutions and gels 245 . For example, in the case of wound healing, proteoglycans were topically applied using 30% glycerol formula 246 . ...
... However, both present side effects limiting their efficacy in a still unclear mechanism. In particular, the Finasteride is known to induce sexual disorder when the oral use is prolonged 245 . The Minoxidil topical application required specific formulation known to induce inflammatory skin reaction, such as eczema and allergy in case of repetitive application 247 . ...
Heparan sulfate proteoglycans (HSPGs) are part of proteoglycan family. They are composed of heparan sulfate (HS)-type glycosaminoglycan (GAG) chains covalently linked to a core protein. By interacting with growth factors and/or receptors, they regulate numerous pathways including Wnt, hedgehog (Hh), bone morphogenic protein (BMP) and fibroblast growth factor (FGF) pathways. They act as inhibitor or activator of these pathways to modulate embryonic and adult stem cell fate during organ morphogenesis, regeneration and homeostasis. This review summarizes the knowledge on HSPG structure and classification and explores several signaling pathways regulated by HSPGs in stem cell fate. A specific focus on hair follicle stem cell fate and the possibility to target HSPGs in order to tackle hair loss are discussed in more dermatological and cosmeceutical perspectives.
... FIN loaded microemulsions with increased permeability of the skin to FIN has also been demonstrated [17]. Gel formulations based on propylene glycol, Tween 80 and sodium lauryl sulphate displayed 6-fold increment cumulative FIN release, flux, partition coefficient, input rate, lag time and diffusion coefficient [18]. ...
Finasteride (FIN), a 5-α reductase enzyme inhibitor is mainly used orally for the treatment of androgenic alopecia and benign prostate hyperplasia. The present study was undertaken for systematic optimization and assessment of the designed nanostructured lipid carriers (NLC) to enhance follicular delivery of FIN by topical administration. The NLCs were prepared by microemulsion method, by employing a 3³ Box-Behnken design and subsequently confirmed by ANOVA analysis. Compritol ATO-888 and Fenugreek oil were selected as the solid lipid and liquid lipid respectively for the fabrication of NLCs. The formulations were characterized for particle size, zeta potential, entrapment efficiency, storage stability and in vitro drug release profile. Morphological profile of the NLCs nanocarriers was studied by transmission electron microscopy (TEM). The Fourier Transform Infrared Spectroscopy (FT-IR) spectrum and differential scanning calorimetry (DSC) thermogram demonstrated that FIN entrapment within NLCs was devoid of chemical interaction with the components. The prepared NLCs had satisfactory particle dimensions, zeta potential and entrapment efficiency. The numerical optimization process indicated the optimal NLC composition with 3 mg of SPC, 6 mg lipid and 5 mg of drug. NLCs loaded with FIN had acceptable particle size at 379.8 nm, zeta potential of −37.1 mV and an entrapment efficiency of 84%. Transmission electron microscopy indicated the spherical morphology. In vitro release profile indicated a fast initial release and subsequently a prolonged release of FIN from the carrier for 24 h. The release kinetics data displayed a Higuchi diffusion release model with the best match R² value (0.848). Short-term stability tests conducted over 4 weeks at 6° and 25°C demonstrated that the formulation could retain their initial properties during the test period.
... The top layer of the skin is comprised of the stratum corneum which acts as a main physical barrier for drug penetration and permeation through the skin. 17 In the past, several FNS topical delivery systems were reported including polymersome, vesicular nanocarriers (ethosome and liposome), liquid crystalline nanoparticles, 0.25% solution, polymeric nanoparticles, matrix system and liposomal gel, etc. [18][19][20][21][22][23][24] There is a growing interest in nanoemulsion based drug delivery systems for lipophilic bioactive components such as antimicrobial agents, anti-inflammatory agents, vitamins and anti-cancerous agents. The introduction of bioactive components into the emulsion enhances their physical and chemical durability, provides functional properties and increases systemic bioavailability and transdermal permeability which influence the characteristics of their end-use in medicinal products or cosmetics. ...
Introduction:
The current work aimed to formulate a novel chitosan-based finasteride nanosystem (FNS-NS) for skin delivery to optimize the drug availability in skin for a longer time and enhance ex vivo performance of finasteride against androgenic alopecia.
Methods:
Both undecorated and chitosan decorated FNS-NSs were synthesized by a high energy emulsification technique. All the prepared nanosystems were further subjected to physicochemical characterizations like pH, viscosity, encapsulation efficiency, surface morphology and in vitro drug release behavior. The influence of the nanosystem on the drug permeation and retention in rat skin was examined using Franz diffusion cell apparatus.
Results:
The droplet size of developed nanosystems ranged from 41 to 864 nm with a low polydispersity index. The zeta potential of the nanosystems was between -10 mV and +56 mV. This chitosan decorated nanosystem exhibited controlled drug release, ie about 78-97% in 24 h. Among all the nanosystems, our chitosan decorated formulation (F5) had low drug permeation (16.35 µg/cm2) and higher drug retention (10.81 µg/cm2).
Conclusion:
The abovementioned results demonstrate satisfactory in vitro drug release, skin retention profiles and ex vivo performance with chitosan decorated FNS-NS (F5). This optimized formulation could increase drug availability in skin and could become a promising carrier for topical delivery to treat androgenic alopecia.
... The liposomal gel, having methylcellulose 2%, and liposomal dispersion demonstrated the enhancement of drug permeation as well as the highest flux and enhancement ratio as compared to the control formulation, i.e., hydroalcoholic solution. This higher permeation enhancement was attributed to higher fluidization of lipid bilayer of skin as a fallout of its stronger interaction with the liposomal phospholipid component [63]. Table 5 presents a summary of studies with liposomal systems for skin targeting. ...
The pilosebaceous unit is the triad comprising of hair follicle, arrector pilli muscle, and sebaceous gland. Drug delivery to and through the hair follicles has garnered much attention of the researchers and the hair follicles represent an attractive target site via topical applications. They are bordered by capillaries and antigen-presenting cells, connected to the sebaceous glands and the bulge region of the hair follicle anchors the stem cells. The nano lipid carriers have the propensity to penetrate through the skin via transcellular route, intracellular route and follicular route. It has been established that nano lipid carriers have the potential for follicular drug delivery and provide some advantages over conventional pathways, including improved bioavailability, enhanced penetration depth, fast transport into the skin, tissue targeting and form a drug reservoir for prolong release. This review describes the pilosebaceous unit (PSU) and related diseases and the recent lipid-based nanotechnology approaches for drug delivery to the follicular unit as well as related tissues. Different types of nano lipid carriers including ethosomes, liposomes, nanoparticles, solid lipid nanoparticles (SLNs), and nano lipid carriers (NLCs) have been reported for follicular drug delivery. Targeted drug delivery with nano-lipid carriers has the potential to augment the efficacy of drugs/bioactives to treat diseases of PSU. This review systematically introduces the activities of different formulations and use of nano lipid carriers in treating PSU related disorders like alopecia, acne, and hirsutism.
... In particular, it affects up to 50% of the middle-aged males and 95% of 80-year-old men. 1 This hair loss perturbs self-esteem, and this decrease in self-esteem may lead to dissatisfaction and depression. In the treatment of AGA, finasteride and its derivatives are approved and currently used, 2 while Minoxidil (MXD), a vasodilator, is the most commonly used drug used as therapy for AGA. MXD exerts a vasodilator effect on hair follicles by leading directly to the proliferation of dermal papilla cells. ...
Purpose:
We designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice.
Methods:
N-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively.
Results:
The ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90-300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD.
Conclusion:
We designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).
Alopecia is a treatable benign disease, however, approximately 15-30% of women and 50% of men suffer from alopecia, which greatly affects patient's self-esteem and quality of life. Currently, commercial products for alopecia treatment include topical minoxidil solution, oral finasteride tablets and oral baricitinib tablets. However, the barrier of stratum corneum, systemic adverse effects and poor cure rate limit the application of commercial products. Therefore, researchers investigated the mechanism of alopecia, and developed new drugs that could target lactate dehydrogenase-related pathways, remove excessive reactive oxygen in hair follicles, and reduce the escape of hair follicle stem cells, thus injecting new strength into the treatment of alopecia. Moreover, starting from improving drug stratum corneum penetration and reducing side effects, researchers have developed hair loss treatment strategies based on dissolved microneedles (MNs), such as drug powders/microparticles, nanoparticles, biomimetic cell membranes, phototherapy and magnetically responsive soluble microneedles, which show exciting alopecia treatment effects. However, there are still some challenges in the practical application of the current alopecia treatment strategy with soluble microneedles, and further studies are needed to accelerate its clinical translation.
Background:
Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition, and volatilization, restrict its development and application in external preparations.
Objective:
This study focused on the preparation of stable nicotine-encapsulated ethosomes.
Methods:
During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced through the synergistic action of osmotic promoters and phosphatidylcholine in binary ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size, particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in isolated mouse skin samples were observed using laser confocal scanning microscopy.
Results:
When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the most stable, had the highest encapsulation rate (86.13±1.40), smallest particle size (106.0±11.0) nm, maximum transdermal depth (180 μm), and maximum fluorescence intensity (160 AU). Nicotine-encapsulated ethosomes (ethanol: PG=5:5, w/w) were an efficient and stable transdermal delivery system.
Conclusion:
The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe and reliable as a transdermal administration agent, which does not irritate the skin.
