Effects of Malaysian thermal spring water as adjunct therapy for mild to moderate acne vulgaris - a prospective, randomised, controlled, split face study.

INTRODUCTION: Acne is a common skin disease with a high psychosocial burden, affecting mostly adolescents and youth worldwide. Management of acne is often challenged by cutaneous side effects that leads to therapeutic intolerance, poor compliance and impaired efficacy. MATERIALS AND METHODS: This was a single-centre, evaluatorblinded, split-face, randomised study investigating the effects of thermal spring water (TSW) in improving efficacy and tolerability of standard acne therapy. Total of 31 participants with mild-to-moderate acne were recruited and subjected to TSW spray to one side of the face 4 times daily for 6 weeks in addition to standard therapy. The other side received standard therapy only. RESULTS: Six (19.4%) males and 25 (80.6%) female with mean age 25.1±6.13 participated, 15 (48.4%) had mild acne while 16 (51.6%) had moderate acne. Seven (22.6%) were on oral antibiotics, 25 (80.6%) used adapalene, 6 (19.4%) tretinoin and 21 (67.7%) benzoyl peroxide. Skin hydration improved and better on spring water treated side with mean difference12.41±30.31, p = 0.04 at the forehead, 39.52±65.14, p < 0.01 at the cheek and 42.172±71.71, p < 0.01 at the jaw at week 6. Participants also report significant reduction in dryness at the treated side at week 6, mean difference 0.93±0.10, p < 0.001. TEWL, sebum and pH were comparable on both sides with no significant differences. Tolerability towards standard therapy improved as early week 2 with reduction of stinging following application of topical therapy (mean difference 0.62±1.43, p = 0.03), increase in skin feeling good (-1.79±1.70, p < 0.001) and skin suppleness (0.62±1.43, p < 0.001). These improvements were significantly maintained till week 6. Cardiff acne disability index significantly improved at week 6 (p<0.001) despite no significant changes in Comprehensive Acne Severity Scale score before and after treatment. CONCLUSION: TSW may have a role as an adjunct to standard acne therapy by improving hydration, acne disability index and tolerability towards standard topical treatment.

‬‬‬‬‬‬‬‬Development and characterization of polymeric nanoparticle-based formulation of adapalene for topical acne therapy‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬.

The purpose of this study is to develop a new formulation of adapalene for the topical treatment of acne. We investigated applicability of polymeric nanocarriers based on tyrosine-derived nanospheres (TyroSpheres) for adapalene delivery. TyroSpheres effectively encapsulated adapalene and substantially enhanced its aqueous solubility, while decreasing the crystallinity of the drug in the formulation. Skin distribution of adapalene via TyroSphere formulation was evaluated ex vivo using human cadaver and porcine ear skin, and this was compared with the commercial adapalene formulation, Differin®. Sustained drug release across stratum corneum in 51 h was observed from TyroSpheres. Additionally, in vitro skin irritation studies demonstrated that encapsulation of adapalene in TyroSpheres significantly reduced the irritancy of the drug to monolayer HaCaTs and reconstituted human epidermis (EpiDerm™, MatTek Corp.). The results suggest that TyroSpheres provide a promising carrier system to deliver hydrophobic drugs to hair follicles and upper epidermis while minimizing skin irritation of the encapsulated drug.

Intradermal and follicular delivery of adapalene liposomes.

BACKGROUND: Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance. OBJECTIVE: To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties. METHODS: A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles. RESULTS: The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66 ± 3.5 nm in diameter and encapsulation efficiency of 97.01 ± 1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72 ± 0.83 µg/cm(2)) in hair follicles than gel (3.33 ± 0.26 µg/cm(2)) and drug solution (1.62 ± 0.054 µg/cm(2)). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation. CONCLUSION: Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.

Acid-responsive polymeric nanocarriers for topical adapalene delivery.

PURPOSE: The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery. METHODS: The anti-acne agent, adapalene, was encapsulated in acid-responsive polymer (Eudragit® EPO) nanocarriers via nanoprecipitation. The nanocarriers were characterized in terms of particle size, surface morphology, drug-carrier interaction, drug release and permeation. RESULTS: Adapalene experienced a rapid release at pH 4.0 in contrast to that at pH 5.0 and 6.0. The permeation study using silicone membrane revealed a significant higher drug flux from the nanocarrier (6.5 ± 0.6 µg.cm(-2).h(-1)) in comparison to that (3.9 ± 0.4 µg.cm(-2).h(-1)) in the control vehicle (Transcutol®). The in vitro pig skin tape stripping study showed that at 24 h post dose-application the nanocarrier delivered the same amount of drug to the stratum corneum as the positive control vehicle did. CONCLUSIONS: The acid-responsive nanocarriers hold promise for efficient adapalene delivery and thus improved acne therapy.

Properties of neural crest-like cells differentiated from human embryonic stem cells.

Neural crest cells (NCCs) derive early in vertebrate ontogenesis from neural tube as a population of migratory cells with exquisite differentiation potential. Abnormalities in NCC behaviour are cause of debilitating diseases including cancers and a spectrum of neurocristopathies. Thanks to their multilineage differentiation capacity NCCs offer a cell source for regenerative medicine. Both these aspects make NCC biology an important issue to study, which can currently be addressed using methodologies based on pluripotent stem cells. Here we contributed to understanding the biology of human NCCs by refining the protocol for differentiation/propagation of NCClike cells from human embryonic stem cells and by characterizing the molecular and functional phenotype of such cells. Most importantly, we improved formulation of media for NCC culture, we found that poly-L-ornithine combined with fibronectin provide good support for NCC growth, we unravelled the tendency of cultured NCCs to maintain heterogeneity of CD271 expression, and we showed that NCCs derived here possess the capacity to react to BMP4 signals by dramatically up-regulating MSX1, which is linked to odontogenesis.

Resolving acne with optimized adapalene microspongeal gel, in vivo and clinical evaluations.

In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 33. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.

Unraveling the pharmaceutical and clinical relevance of the influence of syringic acid loaded linoleic acid transferosomes on acne.

Natural medicines are promising platforms for competent topical treatment modalities benefiting the cosmetic implementation and proffering solutions to the current remedies. Therefore, the objective of this study was to formulate syringic acid (SA), well-known for its multilateral anti-inflammatory, antimicrobial and antioxidant potentials, in newly developed linoleic acid (LA) transferosomes as an anti-acne nano-form remedy. Herein, LA was incorporated in transferosomes owing to its antimicrobial effect and dermal penetrability. Comprehensive appraisal through physicochemical, antioxidant and dermal deposition investigations was conducted. Clinical assessment was also performed in acne patients and compared with the marketed product (Adapalene® gel). The relevant investigations of the optimum formula indicated stable vesicles with a small-sized diameter (147.46 nm), surface charge (-26.86 mV), spherical architecture, reasonable entrapment (76.63%), considerable antioxidant activity (IC50 = 11.1 µg/mL) and remarkable skin deposition (78.72%).More importantly, LA based transferosomes enclosing SA exhibited inflammation lessening in acne sufferers as manifested by greater reduction in the total count of the acne lesions reaching 79.5% in contrast to Adapalene® gel with only 18.7% reduction in acne lesions. Interestingly, no irritation and erythema were reported for the proposed transferosomes. Inclusively, the cosmetic formulation practice could reap benefits of the development of such vesicles.

Screening of Adapalene Microsponges Fabrication Parameters with Insight on the In vitro Biological Effectiveness.

Purpose: The objective of the present study was to scrutinize the microsponges (MS) as a carrier system using Adapalene (ADA) as a model drug. Methods: Data modelling was implemented using Plackett-Burman design to identify the main variables affecting the formulation of ADA-MS. The adopted method of preparation for MS was quasi-emulsion solvent diffusion method. The nominated independent variables were volume of organic phase, sonication time, stirring speed, drug percent, polymer type, emulsifier concentration, and method of organic phase addition. As for the dependent variables, they included entrapment efficiency (E.E.%), production yield (P.Y.%), particle size (P.S.) and morphology. Furthermore, selected ADA loaded microsponges (ADA-MS) were in vitro assayed for their biological activities via cytotoxicity, UVA irradiation and cell viability, and antimicrobial activity. Results: The study indicated that the drug percent, polymer type and surfactant concentration have the key significant effect on E.E.% and P.Y.%, while, the drug percent, stirring speed and volume of organic phase have had a significant effect on P.S. and their morphology. Furthermore, ADA-MS had a momentous cytotoxic effect on A431 and M10 cell-lines with exceptional enrichment when the polymer Eudragit RS100 was used. Also, the ADA-MS increased the cell viability after UVA irradiation on HFB-4 cell-line by 14% to 43%, especially when using Ethyl Cellulose as a polymer. Lastly, the antimicrobial activity of ADA against Propionibacterium acnes was boosted when incorporated into MS. Conclusion: The Plackett-Burman design proved its impact in discerning preparation variables affecting the quality of ADA-MS formulation, with heightening of the in vitro biological activities of ADA. Thus, MS was presumed to be an auspicious carrier system for ADA.

MSCA-1/TNAP selection of human jaw periosteal cells improves their mineralization capacity.

Human jaw periosteum-derived cells (JPCs) represent an alternative cell source to bone marrow-derived mesenchymal stem cells for tissue engineering applications in the oral and maxillofacial surgery. In this study we investigated how far the presence or expression of human mesenchymal stem cell antigen-1/tissue non-specific alkaline phosphatase (MSCA-1/TNAP) and LNGFR (CD271) can be utilized to select and enrich the osteogenic progenitor cell fraction from the entire JPC population. Depending on their mineralization capacity, we classified the human isolated JPCs into mineralizing (mJPCs) and non-mineralizing JPCs (nmJPCs). Flow cytometric analyses revealed that undifferentiated mJPCs expressed MSCA-1/TNAP at significant higher levels than nmJPCs at day 5 and 10 of osteogenesis. Western blot analyses showed increased MSCA-1/TNAP expression levels in mJPCs during osteogenesis, whereas in nmJPCs MSCA-1/TNAP expression remained undetectable. Using the MSCA-1 and LNGFR specific antibodies, we separated the positive and negative fractions from the entire mJPC population. In order to analyse the mineralization capacity of the MSCA-1(+) and LNGFR(+) cell subsets, we quantified the calcium deposition in both subpopulations in comparison to the respective negative subpopulations. The MSCA-1(+)/TNAP(+) cell fraction showed a significant higher osteogenic capacity compared to the MSCA-1-/TNAP- cell fraction whereas the LNGFR(+/-) cell fractions did not differ in their osteogenic potential. Our findings suggest that MSCA-1 may represent a promising osteogenic marker for mJPC.

Adapalene-loaded poly(ε-caprolactone) microparticles: Physicochemical characterization and in vitro penetration by photoacoustic spectroscopy.

Adapalene (ADAP) is an important drug widely used in the topical treatment of acne. It is a third-generation retinoid and provides keratolytic, anti-inflammatory, and antiseborrhoic action. However, some topical adverse effects such as erythema, dryness, and scaling have been reported with its commercial formula. In this sense, the microencapsulation of this drug using polyesters can circumvent its topical side effects and can lead to the enhancement of drug delivery into sebaceous glands. The goal of this work was to obtain ADAP-loaded poly(ε-caprolactone) (PCL) microparticles prepared by a simple emulsion/solvent evaporation method. Formulations containing 10 and 20% of ADAP were successfully obtained and characterized by morphological, spectroscopic, and thermal studies. Microparticles presented encapsulation efficiency of ADAP above 98% and showed a smooth surface and spherical shape. Fourier transform infrared spectroscopy (FTIR) results presented no drug-polymer chemical bond, and a differential scanning calorimetry (DSC) technique showed a partial amorphization of the drug. ADAP permeation in the Strat-M membrane for transdermal diffusion testing was evaluated by photoacoustic spectroscopy (PAS) in the spectral region between 225 and 400 nm after 15 min and 3 h from the application of ADAP-loaded PCL formulations. PAS was successfully used for investigating the penetration of polymeric microparticles. In addition, microencapsulation decreased the in vitro transmembrane diffusion of ADAP.

Incorporation of benzoyl peroxide nanocrystals into adapalene-loaded solid lipid microparticles: Part I - Nanocrystalline benzoyl peroxide.

Hair follicles are a promising target for the administration of drugs to treat diseases associated with the pilosebaceous unit, such as acne. For solid lipid microparticle dispersions a successful and selective delivery of adapalene via targeted erosion of the particles in sebum has been shown. By embedding nanoparticulate benzoyl peroxide in lipid microparticles, the therapeutic potency of adapalene can be further increased by improving follicular deposition of benzoyl peroxide and minimizing direct contact between benzoyl peroxide and stratum corneum, which is responsible for the irritating potential of this active agent. The aim of this study was to develop a novel nanoparticulate formulation for benzoyl peroxide suitable for the incorporation in solid lipid microparticles. In this contribution, a wet grinding process using liposomal dispersions of fully hydrated phosphatidylcholine was developed, upscaled and optimized for solid content and stabilizer concentration. The resulting novel nanosuspension was characterized by particle size and morphology and examined for chemical and physical stability as well as solubility and polymorphism. During the process development a dependency between the colloidal microstructure of the stabilizer dispersion and milling efficiency was found: while physical mixtures fail to deliver nanosuspensions, liposomal dispersions succeed with the same amount of stabilizer.

Will the polyphenol and adapalene combination be a good strategy on acne vulgaris?

Acne vulgaris is a common disease which affects about 85% of the population. Various topical drugs are available, but the retinoid derivatives are mostly taken into consideration. They are used as a first-line treatment drugs. However, they also have few side effects. Whereas, adapalene which is a third generation topical retinoid has fewer side effects compared to other derivatives. In this, we hypothesize that the combination therapy of adapalene and flavonoid could improve the efficacy and thereby it can also decrease the treatment time. Since, flavonoids possess multiple activities we assume that it can improve the action of the drug by showing a synergistic activity. Moreover, when we incorporate these two drugs in nanoemulgel, it can easily penetrate into the skin and produce its therapeutic action. Hence, we assume that if this hypothesis proves to be correct then this method will be an effective one in treating acne (pustule).

Multi-drug hybrid delivery systems with distinct release profiles based on gelatin/collagen containing vesicles derived from block copolymers.

Hybrid delivery systems can release multiple drugs with different profiles and have several applications, including skin dressing. In this work, the co-solvent technique was used for the preparation of nanometric vesicles based on poly(styrene-b-ethylene oxide) block copolymer (BCPVs) containing adapalene (AD). The BCPVs were incorporated into collagen and gelatin matrices together with free AD and silver sulfadiazine (SSD). The AD content of BCPVs and their release capacity were analyzed by using ultraviolet-visible spectroscopy (UV-Vis). The gelatin and collagen matrices were evaluated for their ability to release AD and SSD through an in vitro release study. The obtained results confirmed that the production of empty and AD-loaded BCPVs was viable. The degree of AD encapsulation in BCPVs was 9.0% and the in vitro test revealed a constant, slow, and prolonged release of AD content from AD-loaded BCPVs. The combination of free and encapsulated multiple drugs in hybrid delivery systems based on gelatin and collagen matrices was shown to act as a skin dressing that combined the progressive release of large amounts of drugs within the first hours of use (to restrict infection) with a more prolonged and slow release of AD to enhance skin healing.

Selective delivery of adapalene to the human hair follicle under finite dose conditions using polymeric micelle nanocarriers.

Drug delivery systems that target the pilosebaceous unit (PSU) selectively could improve the clinical management of diseases that originate in the hair follicle. The aims of this study were (i) to prepare polymeric micelles using d-α-tocopheryl polyethylene glycol succinate diblock copolymer that incorporated adapalene (ADA), a retinoid indicated for Acne vulgaris, and (ii) to investigate the feasibility of delivering ADA preferentially to the PSU under finite dose conditions - thereby better approximating actual conditions of use by patients. Incorporation of ADA into spherical micelles (dn <20 nm) increased aqueous solubility by ∼50 000-fold (from <4 ng mL-1 to 0.2 mg mL-1). Optimized micelle solution and gel formulations (0.02% ADA) were stable after storage for 4 weeks at 4 °C. Finite dose experiments using full-thickness porcine and human skin revealed that ADA delivery efficiency from micelle solution and gel formulations was equivalent and was >2- and 10-fold higher than that from Differin® gel and Differin® cream (products containing ADA at 0.1% (w/w)). Follicular delivery studies in human skin, using a punch biopsy technique to extract the intact PSU, demonstrated that the micelle solution and gel formulations did indeed enable preferential delivery of ADA to the PSU (4.5- and 3.3-fold higher, respectively, than that to PSU-free skin biopsies). Confocal laser scanning microscopy provided visual corroboration that ADA was uniformly distributed in the hair follicles. In conclusion, the results confirmed that polymeric micelle nanocarriers enabled selective, targeted drug delivery to the PSU under finite dose conditions and so might improve therapy of follicular diseases and decrease off-site side-effects.

Codelivery of benzoyl peroxide & adapalene using modified liposomal gel for improved acne therapy.

AIM: Current study investigates therapeutic efficacy and tolerability of benzoyl peroxide (BPO)- and adapalene (AD)-loaded modified liposomal gel (BPO-AD-mLipo gel) for improved acne therapy. MATERIALS & METHOD: BPO-AD-mLipo were optimized and loaded in Carbopol gel. Both BPO-AD-mLipo and BPO-AD-mLipo-gel were extensively characterized for different quality attributes. Ex vivo dermal bioavailability, dermal distribution, in vivo anti-acne efficacy and skin irritation studies were performed and compared with marketed formulation (Epiduo®, Galderma Laboratories LP, TX, USA). RESULTS: BPO-AD-mLipo illustrated size 256.4 ± 9.3 nm with polydispersity index âˆ¼ 0.2. Significantly enhanced dermal bioavailability (AD-2.1, 5.4; BPO-3.0, 7.83-fold) and reduction in skin irritation and papule density in animal model were observed with BPO-AD-mLipo-gel as compared with free drugs and Epiduo, respectively. CONCLUSION: BPO-AD-mLipo gel provides effective and safer alternative approach for codelivery of anti-acne drugs.

Utilizing combination therapy for ethnic skin.

A major issue in treating acne in individuals of color is the need to treat and prevent postinflammatory hyperpigmentation (PIH), which is common in this population. This subset analysis reports the pigmentary changes in subjects of color with acne who were enrolled in a community-based trial comparing 3 different topical therapeutic regimens. All subjects received combination clindamycin 1%-benzoyl peroxide (BPO) 5% topical gel containing glycerin and dimethicone. Subjects were randomized to receive this combination therapy in addition to either a tretinoin microsphere (RAM) gel at concentrations of either 0.04% or 0.1% or adapalene (AP) gel 0.1%. There was a trend toward better resolution of hyperpigmentation in the subjects receiving the clindamycin-BPO topical gel in combination with RAM gel 0.04%.

Mechanistic Analysis of Human Skin Distribution and Follicular Targeting of Adapalene-Loaded Biodegradable Nanospheres With an Insight Into Hydrogel Matrix Influence, In Vitro Skin Irritation, and In Vivo Tolerability.

This work aimed at the development of a biocompatible, non-oily nanomedicine for follicular delivery of adapalene (AD) ameliorating its irritation potential for convenient localized topical treatment of acne vulgaris. AD was efficiently incorporated into poly-ε-caprolactone nanospheres (NS) with an encapsulation efficiency of 84.73% ± 1.52%, a particle size of 107.5 ± 8.19 nm, and zeta potential of -13.1 mV demonstrating a sustained-release behavior. The AD-NS were embedded in either hydroxypropyl methylcellulose (HPMC) or hyaluronate (HA) gel. The ex vivo human skin dermatokinetics of AD from each system was studied. The nanoparticles dispersion showed significantly higher AD retention in the epidermis and dermis than AD suspension. NS-HPMC decreased whereas NS-HA increased AD retained in all the skin layers. The fate of the NS and the role of the hydrogel in modulating skin distribution was evaluated by confocal laser scanning microscopy (CLSM) imaging of fluorescently labeled NS. CLSM illustrated follicular localization of the florescent NS. HPMC gel restricted the presence of NS to the stratum corneum and epidermis. HA gel enhanced the penetration of NS to all the skin layers. In vitro skin irritation using human dermal fibroblasts and in vivo animal tolerability studies were performed. Accordingly, HA gel-dispersed AD-NS presented a nonirritant compromised cosmeceutical formulation suitable for oily acneic skin.

Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance.

Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth- 7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate. Further, monitored parameters were strongly affected by sertaconazole nitrate incorporation, while they remained almost unchanged in adapalene-loaded vehicles. In addition, results of the in vivo skin performance study supported acceptable tolerability for all investigated formulations, suggesting selected microemulsions as promising carriers worth exploring further for effective skin delivery of model drugs.

Fast isolation and expansion of multipotent cells from adipose tissue based on chitosan-selected primary culture.

Adipose-derived adult stem cells (ASCs) have gained much attention because of their multipotency and easy access. Here we describe a novel chitosan-based selection (CS) system instead of the conventional plastic adherence (PA) to obtain the primary ASCs. The minimal amount of adipose tissue for consistent isolation of ASCs is reduced from 10 mL to 5 mL. The selection is based on the specific interaction between cells and chitosan materials, which separate ASCs by forming spheroids during primary culture. The primary culture period was reduced from 4 days to one day and more ASCs (ten-fold expansion) were achieved in a week. The average duration for obtaining 1 × 10(7) cells takes about seven days from 5 mL of adipose tissue, compared to 14 days using the conventional PA method from 10 mL of adipose tissue. The replicative senescence of CS-ASCs is not evident until the fifteenth passage (vs. eighth for the PA-ASCs). The obtained ASCs (CS-ASCs) have less doubling time for the same passage of cells and show greater stemness than those obtained from the conventional PA method (PA-ASCs). Moreover, CS-ASCs undergo trilineage differentiation more effectively than PA-ASCs. The greater differentiation potential of CS-ASCs may be associated with the enrichment and maintenance of CD271 positive cells by chitosan selection of primary culture.

Development, formulation, and characterization of an adapalene-loaded solid lipid microparticle dispersion for follicular penetration.

The model retinoid adapalene was formulated in a novel solid lipid microparticle (SLM) dispersion as a topical drug delivery system for transport of the active pharmaceutical ingredient (API) into hair follicle orifices. The aims of the investigations were the solid-state characterization of the lipid matrix (LM) with wide angle X-ray diffraction (WAXD) and hot-stage light microscopy (HS), the design space analysis of the developed SLM dispersion with a Box-Behnken design, the stability study of the manufactured formulation for particle size with laser diffraction and polarization intensity differential scattering (LD/PIDS) and thermal behavior with differential scanning calorimetry (DSC), and the structure analysis of the SLM dispersion with light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The formulation showed a constant mean particle size (MPS) of 4.2 µm over 24 weeks with a melting point of about 56°C. The potential for dermal application was determined by a follicular penetration (FP) study with porcine ear skin and thermal analysis of the interaction with artificial human skin lipids like sebum and stratum corneum lipid mixture. The in vitro studies confirmed both the follicular penetration potential and a targeted erosion or dissolution of the particles in sebum.