Review of Applications and Future Prospects of Stimuli-Responsive Hydrogel Based on Thermo-Responsive Biopolymers in Drug Delivery Systems.

Some of thermo-responsive polysaccharides, namely, cellulose, xyloglucan, and chitosan, and protein-like gelatin or elastin-like polypeptides can exhibit temperature dependent sol-gel transitions. Due to their biodegradability, biocompatibility, and non-toxicity, such biomaterials are becoming popular for drug delivery and tissue engineering applications. This paper aims to review the properties of sol-gel transition, mechanical strength, drug release (bioavailability of drugs), and cytotoxicity of stimuli-responsive hydrogel made of thermo-responsive biopolymers in drug delivery systems. One of the major applications of such thermos-responsive biopolymers is on textile-based transdermal therapy where the formulation, mechanical, and drug release properties and the cytotoxicity of thermo-responsive hydrogel in drug delivery systems of traditional Chinese medicine have been fully reviewed. Textile-based transdermal therapy, a non-invasive method to treat skin-related disease, can overcome the poor bioavailability of drugs from conventional non-invasive administration. This study also discusses the future prospects of stimuli-responsive hydrogels made of thermo-responsive biopolymers for non-invasive treatment of skin-related disease via textile-based transdermal therapy.

Influence of pH-responsive compounds synthesized from chitosan and hyaluronic acid on dual-responsive (pH/temperature) hydrogel drug delivery systems of Cortex Moutan.

The polysaccharide-based pH-responsive compounds, namely, N,N,N-trimethyl chitosan (TMC), polyethylene glycolated hyaluronic acid (PEG-HA), and polysaccharide-based nano-conjugate of hyaluronic acid, chitosan oligosaccharide and alanine [HA-Ala-Chito(oligo)] were chemically synthesized using biopolymers chitosan and hyaluronic acid, and applied here to observe the changes in morphology, pH-stability, mechanical and drug-release behavior, and cytotoxicity of thermo-responsive polymer: Poloxamer 407 (PF127)-based drug delivery systems for traditional Chinese medicine Cortex Moutan (CM). The thermo-responsive hydrogel of PF127 loaded with CM (GelC) was used as control. The dual-responsive (pH/temperature) hydrogels: PF127/TMC/PEG-HA (Gel1) and PF127/HA-Ala-Chito(oligo) (Gel2) showed improved mechanical behavior as obtained by rheology and mechanical agitation study, and pH-stability under various external pH conditions, and those improvements occurred due to the addition of polysaccharide-based pH-responsive compounds in the systems. Both, Gel1 and Gel2 showed better morphology than GelC as obtained by SEM or TEM suggesting that interaction of polysaccharide-based pH-responsive compounds with PF127 in either gel or sol state gave better porous network structure in the hydrogels or more dispersed micellar arrangements in sol-state, respectively. Gel1 showed the highest cumulative drug release (86.5%) after 5 days under mild acidic condition (pH 6.4) suggesting that release behavior of a hydrogel drug carrier was dependent on morphology, mechanical behavior, and pH-stability. The transdermal release (ex-vivo) results indicated that gallic acid, the active marker of CM passed through porcine ear skin and all the formulations showed more or less similar transdermal release properties. The hydrogels loaded with CM showed no cytotoxicity (cell viability >90.0%) on human HaCaT keratinocytes within concentration range of 0.0-20.0 µg/ml as obtained by MTT assay, and cell viability was more than 100% at a concentration of 20.0 µg/ml for Gel2. The formulations without loaded drug namely, Gel1-CM and Gel2-CM exhibited strong anti-bacterial action against gram positive bacteria Staphylococcus aureus.

Drug delivery system of dual-responsive PF127 hydrogel with polysaccharide-based nano-conjugate for textile-based transdermal therapy.

Pluronic F-127 based dual-responsive (pH/temperature) hydrogel drug delivery system was developed involving polysaccharide-based nano-conjugate of hyaluronic acid and chitosan oligosaccharide lactate and applied for loading of gallic acid which is the principal component of traditional Chinese medicine Cortex Moutan recommended in the treatment of atopic dermatitis. The polysaccharide-based nano-conjugate was used as pH-responsive compound in the formulation and its amphiphilic character was determined colorimetrically. Microstructure analysis by SEM and TEM indicated highly porous hydrogel network and well-dispersed micellar structures, respectively, after modification with the nano-conjugate, and so, release property of the hydrogel for drug was significantly improved. Different pH-conditions were applied here to see pH-responsiveness of the formulation and increase in acidity of external environment gradually diminished mechanical stability of the hydrogel and that was reflected on the drug release property. Rheology was performed to observe sol-gel transition of the formulation and showed better rheological properties after modification with nano-conjugate. In this study, the cytotoxicity results of PF127 based formulations loaded with/without gallic acid showed cell viability of > 80.0 % for human HaCaT keratinocytes in the concentration range of 0.0-20.0 µg/ml.

Dual-responsive (pH/temperature) Pluronic F-127 hydrogel drug delivery system for textile-based transdermal therapy.

A dual-responsive hydrogel (pH/temperature) was developed from a thermos-responsive polymer, pluronic F-127 (PF127), and pH-responsive polymers, N,N,N-trimethyl chitosan (TMC) and polyethylene glycolated hyaluronic acid (PEG-HA). Gallic acid, the principal component of the traditional Chinese drug Cortex Moutan was loaded into the hydrogel (PF127/TMC/PEG-HA) for possible application in textile-based transdermal therapy as Cortex Moutan has been proven to be an effective drug for the treatment of atopic dermatitis (AD). TMC and PEG-HA were synthesized, characterized (1H-NMR and FTIR), and added to the formulations to enhance drug release from the hydrogels, and increase the drug targeting of the carriers. The thermo-responsive properties of the hydrogel were assessed by dynamic viscosity analysis and the tube inversion method, and the pH-responsiveness of the formulation was determined by changing the pH of the external media. Rheology study of the hydrogels showed that complex viscosity and storage/loss moduli for PF127/TMC/PEG-HA hydrogel formulation are higher than PF127 hydrogel. The microstructure analysis by reflection SAXS indicated similar type of frozen inhomogeneity of hydrogel formulations. Various characterizations such as FTIR, SEM, TEM, zeta potential, and degradation of the hydrogel formulation indicated that the PF127/TMC/PEG-HA hydrogel showed better physico-chemical properties and morphology than did the PF127 hydrogel, and drug release was also higher for the PF127/TMC/PEG-HA hydrogel than for PF127. The drug release from hydrogels followed more closely first-order rate model than other rate models.

Thermoresponsive Hydrogels and Their Biomedical Applications: Special Insight into Their Applications in Textile Based Transdermal Therapy.

Various natural and synthetic polymers are capable of showing thermoresponsive properties and their hydrogels are finding a wide range of biomedical applications including drug delivery, tissue engineering and wound healing. Thermoresponsive hydrogels use temperature as external stimulus to show sol-gel transition and most of the thermoresponsive polymers can form hydrogels around body temperature. The availability of natural thermoresponsive polymers and multiple preparation methods of synthetic polymers, simple preparation method and high functionality of thermoresponsive hydrogels offer many advantages for developing drug delivery systems based on thermoresponsive hydrogels. In textile field applications of thermoresponsive hydrogels, textile based transdermal therapy is currently being applied using drug loaded thermoresponsive hydrogels. The current review focuses on the preparation, physico-chemical properties and various biomedical applications of thermoresponsive hydrogels based on natural and synthetic polymers and especially, their applications in developing functionalized textiles for transdermal therapies. Finally, future prospects of dual responsive (pH/temperature) hydrogels made by these polymers for textile based transdermal treatments are mentioned in this review.

Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells.

Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

Microencapsulation of Traditional Chinese Herbs-PentaHerbs extracts and potential application in healthcare textiles.

In this work, Traditional Chinese Herbs (TCH)-PentaHerbs--was successfully microencapsulated in chitosan-sodium alginate (CSA) blend matrix using emulsion-chemical cross-linking method and the final product was characterised with regard to structure, surface morphology, particle size, in vitro drug release and skin toxicity by means of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), laser diffraction particle size analysis, high performance liquid chromatography (HPLC) and methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) release assays respectively. Results showed that the microcapsules were in spherical form with diameter mostly in the range of 3-18 µm and that the release performance of the microcapsules was influenced by pH value of phosphate buffer solution (PBS). The microcapsules had no toxic effects on cells and were successfully grafted onto the surface of cotton fabrics. These results indicated that PentaHerbs loaded CSA microcapsule may possess potential application in clinical treatment of atopic dermatitis (AD).

Anti-allergic drug discovery in China for eczema: current methods and future strategies.

INTRODUCTION: Eczema is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for this disease, treatment relies on topical and systemic anti-allergic or immunomodulating therapies. Topical corticosteroids, macrolide immunosuppressants and oral immunomodulating drugs have been the mainstay for the treatment of recalcitrant disease. However, in China as well as throughout Asia, the use of traditional and proprietary topical and herbal medicines is also popular. AREAS COVERED: This article reviews the evidence for the anti-allergic effects of topical and oral forms of these medicinal. The authors also present and discuss the current methods of preparation and evaluation for these traditional and proprietary medications. Additionally, the authors present the novel delivery method of employing nanotechnology to deliver these herbal therapies. EXPERT OPINION: Many herbal concoctions have had trials which have claimed therapeutic benefits for eczema. However, the scientific methods in these trials are often flawed and often not objective. In fact, the majority of these trials do not provide proof of objective efficacy for the anti-allergic effects claimed. It is felt that the delivery of herbal medication by nanotechnology has several crucial challenges that certainly need to be overcome for the optimal design of therapies for eczema, through optimizing material properties, methods of delivery and understanding the mechanisms of action.

Preparation and characterisation of chitosan microcapsules loaded with Cortex Moutan.

The process of preparation and characterisation of chitosan microcapsules loaded with Cortex Moutan was studied and the optimum condition for microcapsule preparation was investigated by orthogonal array analysis. Based on the yield percentage of microcapsule, the optimum condition for microcapsule preparation was (i) core-shell ratio=1:2; (ii) chitosan concentration=6% (w/v); (iii) agitation speed=1100 rpm; and (iv) cross-linking time=90 min. Meanwhile, relative importance of the preparation parameters was in the order: core-shell ratio, agitation speed, chitosan concentration and cross-linking time. The Fourier transform infrared spectroscopy analysis revealed that Cortex Moutan has been completely encapsulated into chitosan microcapsule. The release rate of Cortex Moutan from microcapsules in pH 5.4 phosphate buffered saline (PBS) was slightly better than that in pH 5.0 PBS after the initial 48 h and the release rate became steady after that.