Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing

Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine.     

Antifouling properties of hydrogels

Abstract

Marine sessile organisms easily adhere to submerged solids such as rocks, metals and plastics, but not to seaweeds and fishes, which are covered with soft and wet ‘hydrogel’. Inspired by this fact, we have studied long-term antifouling properties of hydrogels against marine sessile organisms. Hydrogels, especially those containing hydroxy group and sulfonic group, show excellent antifouling activity against barnacles both in laboratory assays and in the marine environment. The extreme low settlement on hydrogels in vitro and in vivo is mainly caused by antifouling properties against the barnacle cypris.     

Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m²/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.     

Injectable melatonin-loaded carboxymethyl chitosan (CMCS)-based hydrogel accelerates wound healing by reducing inflammation and promoting angiogenesis and collagen deposition

Carboxymethyl chitosan(CMCS)-based hydrogels have antibacterial activity,and have shown the abilities of preventing wound infection,promoting cell proliferation,accelerating collagen deposition,and stimulating hyaluronic acid formation during wound healing.As a hormone produced by the pineal gland in humans and animals,melatonin promotes skin wound healing by regulating the release of inflammatory mediators and accelerating the proliferation and migration of cells,angiogenesis,and collagen deposition.However,the combined effects of CMCS and melatonin on wound healing remain unclear.Injectable CMCS-based hydrogels containing melatonin were prepared,and their healing effects were evaluated using a full-thickness cutaneous wound model in rats.Compared with the control and the hydrogel with no melatonin groups,the melatonin-loaded hydrogel significantly increased the percentage of wound closure,promoted the proliferation of granulation tissue and re-epithelialization,and accelerated collagen deposition.Additionally,the melatonin-loaded hydrogel promoted angiogenesis and vascular endothelial growth factor receptor protein expression and increased the expression of cyclooxygenase-2 and inducible nitric oxide synthase.The melatonin-loaded hydrogel also markedly increased the expression of collagen III,α-smooth muscle actin,and transforming growth factor-β1 proteins and reduced collagen I expression.These results suggest that the melatonin-loaded hydrogel promoted granulation tissue formation and accelerated wound healing by reducing inflammation and promoting angiogenesis and collagen deposition.     

Rheological and thermal characteristics of a two phase hydrogel system for potential wound healing applications

Hydrogels fabricated from single polymers have been extensively investigated for wound healing applications. However, in many cases a single polymer cannot meet divergent demands in terms of both properties and performance. In this work, a two phase hydrogel was prepared by physically imbedding a xerogel in the core of a freeze thawed hydrogel. The outer hydrogel was prepared by freeze thawing poly (vinyl alcohol) (PVA) and poly (acrylic acid) (PAA) while the xerogels were prepared by UV polymerisation of 1-vinyl-2-pyrrolidinone (NVP). The rheological results indicated that the two phase hydrogels over a period of 2 weeks formed a strong interface and demonstrated greater physical strength. This suggested that the inner gel containing PVP diffused into the PVA/PAA hydrogel, which in turn increased hydrogen bonding, resulting in the overall increase in the stiffness of the gel. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirmed hydrogen bonding had occurred between the constituents of the two phase hydrogels. Thermal analysis suggested that T _g of each of the samples was above 80 °C, which indicated no impact on the behaviour of the gel at body temperature, but did however, give an indication of the stiffness of the dry polymer.     

Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: preparation,characterization, and in vitro drug release study

Context: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. Objective: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. Methods: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez® 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. Results and Discussion: Nanocapsules showed mean particle size and zeta potential of 201 ± 6 and ?5.73 ± 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 ± 2.96 mg/cm²/h^1/2) compared to the hydrogels containing the free drug (k = 26.65 ± 2.09 mg/cm²/h^1/2). Conclusion: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.     

Evaluation of hydrogels for soft tissue adhesives <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> analyses

In this study, natural materials (sodium alginate, dextran, gelatin and carboxymethyl chitosan) were modified to get aldehyde components and amino components. Upon mixing the two-component solutions together, four kinds of Schiff base hydrogels formed successfully within 5-300 s and could seal the wound tissue. The cytotoxicity tests of hydrogel extraction solution confirmed that the hydrogels are nontoxic materials. The adhesive ability was evaluated in vivo by measuring the adhesive strength after sealing the skin incisions on the back of rats. All the hydrogels showed higher adhesive strength than that of commercial fibrin glue and the blank control. The histological staining observation by hematoxylin and eosin staining (HE) and Masson’s trichrome staining (MTC) methods suggested that the hydrogels had good biocompatibility and biodegradation in vivo. They have only normal initial inflammation to skin tissue and could improve the formation of new collagen in the incision section. So, the prepared hydrogels were both safe and effective tissue adhesive, which had the great potentials to be used as skin tissue adhesive.     

Radiation synthesis of PVP/alginate hydrogel containing nanosilver as wound dressing

Hydrogels with polyvinyl pyrrolidone (PVP) and alginate were synthesized and silver nanoparticles were incorporated in hydrogel network using gamma radiation. PVP (10?and 15?%) in combination with 0.5?and 1?% alginate was gamma irradiated at different doses of 25?and 40?kGy. Maximum gel percent was obtained with 15?% PVP in combination with 0.5?% alginate. The fluid absorption capacity for the PVP/alginate hydrogels was about 1881–2361?% at 24?h. Moisture vapour transmission rate (MVTR) of hydrogels containing nanosilver at 24?h was 278.44?g/(m²h). The absorption capacity and moisture permeability of the PVP/alginate–nanosilver composite hydrogel dressings show the ability of the hydrogels to prevent fluid accumulation in exudating wound. The hydrogels containing nanosilver demonstrated strong antimicrobial effect and complete inhibition of microbial growth was observed with 70?ppm nanosilver dressings. PVP/alginate hydrogels containing nanosilver with efficient fluid handling capacity and antimicrobial activity was found suitable for use as wound dressing.     

Formulation and rheological evaluation of ethosome-loaded carbopol hydrogel for transdermal application

Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50–80?Pa at low polymer concentration, (ii) relatively frequency independent elastic (G′) and viscous (G″) properties and (iii) thermal stability.

Methods: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G′ and G″) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control.

Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50 and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G′ and G″. Furthermore, the flow and viscoelastic properties were maintained at the 4, 25 and 32?°C. The results from in vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation.

Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles.     

Improved tretinoin photostability in a topical nanomedicine replacing original liquid suspension with spray-dried powder with no loss of effectiveness

Objective: The use of spray-dried powders containing tretinoin-loaded nanocapsules instead of the original liquid suspension, aimed at the preparation of dermatological nanomedicines with improved photostability, was investigated.

Methods: Powders were prepared using lactose as a drying adjuvant. Hydrogels were prepared using two approaches: dispersing Carbopol Ultrez 10^® in an aqueous redispersion of the powder or incorporating the powder in previously formed hydrogels.

Results and discussion: The photodegradation of tretinoin in hydrogels prepared with the powders showed similar half-life times (around 19.5 h) compared to preparations with the original liquid nanocapsules (20.7 ± 1.4 h), regardless of the preparation approach. In addition, the topical nanomedicines prepared with the spray-dried powders presented a significant improvement in tretinoin photostability compared to the formulation containing the non-encapsulated drug.

Conclusion: This study verified that the addition of the spray-dried powders containing tretinoin-loaded lipid-core nanocapsules to hydrogels did not influence the photoprotection of the drug compared with the preparation procedure using the original liquid suspension.     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Bioactive injectable triple acting thermosensitive hydrogel enriched with nano-hydroxyapatite for bone regeneration: in-vitro characterization,Saos-2 cell line cell viability and osteogenic markers evaluation

Hydrogels forming in-situ have gained great attention in the area of bone tissue engineering recently, they were also showed to be a good and less invasive alternative to surgically applied ones. The primal focus of this study was to prepare chitosan-glycerol phosphate thermosensitive hydrogel formed in-situ and loaded with risedronate (bone resorption inhibitor) in an easy way with no requirement of complicated processes or large number of equipment. Then we investigated its effectiveness for bone regeneration. In-situ forming hydrogels were prepared using chitosan cross-linked with glycerol phosphate and loaded with risedronate and nano-hydroxyapatite as bone cement. The prepared hydrogels were characterized by analyzing their gelation time at 37?°C, % porosity, swelling index, in-vitro degradation, rheological properties, and in-vitro drug release. Results showed that the in-situ hydrogels prepared using 2.5% (w/v) chitosan cross-linked with 50% (w/v) glycerol phosphate in the ratio (9:1, v/v) reinforced with 20?mg/mL and nano-hydroxyapatite possessed the most sustained drug release profile. This optimized formulation was further evaluated using DSC and FTIR studies, in addition to their morphological properties using scanning electron microscopy. The effect on Saos-2 cell line viability was evaluated also using MTT assay on the optimized hydrogel formulation in addition to their action on cell proliferation using fluorescence microscope. Moreover, calcium deposition on the hydrogel and alkaline phosphatase activity were evaluated. Risedronate-nano-hydroxyapatite loaded hydrogels significantly enhanced the Saos-2 cell proliferation in addition to enhanced alkaline phosphatase activity and calcium deposition. Such results suggest that risedronate-nano-hydroxyapatite loaded hydrogels present great biocompatibility for bone regeneration. Proliferation of cells, as well as deposition of mineral on the hydrogel, was an evidence of the biocompatible nature of the hydrogel. This hydrogel formed in-situ present a good less invasive alternative for bone tissue engineering.     

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full‐Thickness Skin Regeneration During Wound Healing

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full‐thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid‐graft‐dopamine and reduced graphene oxide (rGO) using a H₂O₂/HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self‐healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full‐thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full‐thickness skin repair.     

Rheological,mechanical, and bioadhesive behavior of hydrogels to optimize skin delivery systems

Background: Hydrogels are widely used for cutaneous formulations; thereby comparing the bioadhesive properties of polymers with a view to prolong the residence time of topical drugs on the skin would be very useful to design novel topical drug delivery systems.

Aim: The objective of this study was to correlate data from rheological studies and texture profile analysis, with bioadhesion on the skin.

Methods: Polyacrylic acid polymers used were carbomer homopolymer type A (C971) and type B (C974), and polycarbophil (PP) dispersed in water at various concentrations (0.1, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0%, w/v). Rheological, texture, and bioadhesive properties were determined to compare the hydrogels.

Results: Rheological analysis showed that all samples exhibited pseudoplastic behavior with thixotropy. Texture profile analysis showed that compressibility, hardness, and adhesiveness of the hydrogels were dependent on the polymer concentration, and the cohesion values were high. Bioadhesion of C974 and PP at 0.5 and 2% was of the same magnitude, while all samples of C971 had lower values. The bioadhesion of 5% C974 was the highest, while that 5% PP was lower, possibly because PP showed the greatest hardness and this rigidity may decrease the interaction of the polymer with the skin.

Conclusion: A comprehensive comparative rheological and textural analyses of several polymers for topical systems were undertaken in terms of their bioadhesion. Therefore, it is possible to conclude that these polymers can be used for optimization of drug delivery systems on the skin.     

A methacrylic hyaluronic acid derivative for potential application in oral treatment of celiac disease

Objective: Aim of this work was the synthesis of a methacrylic hyaluronic acid (HA) derivative and the production, via photocrosslinking, of related hydrogels loaded with an endopeptidase intended for a potential oral treatment of celiac disease.

Methods: The methacrylic derivative of HA was prepared through a one-pot procedure involving the reaction with ethylenediamine (EDA) and methacrylic anhydride (MA). The obtained derivative, named HA-EDA-MA, was used to prepare photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained hydrogels were recovered as gels or freeze-dried powders.

Results: Hydrogels obtained as freeze-dried powders, are able to protect loaded enzyme from degradation due to freeze-drying process and from alteration during storage, overall in the presence of a cryoprotectant. All photocrosslinked HA-EDA-MA hydrogels (gels and powders) release PEP FM in simulated intestinal fluid in sustained manner and in active form. HA-EDA-MA hydrogels are nontoxic as demonstrated through in vitro studies on BALB 3T3 cells.

Conclusions: Prepared hydrogels show a potential application for oral treatment of celiac disease thanks to the possibility to release enzymes able to detoxify the gliadin peptide that induces the immunogenic response.     

Natural Carrier-Free Binary Small Molecule Self-Assembled Hydrogel Synergize Antibacterial Effects and Promote Wound Healing by Inhibiting Virulence Factors and Alleviating the Inflammatory Response

Methicillin-resistant Staphylococcus aureus (MRSA)-infected skin wounds have caused a variety of diseases and seriously endanger global public health. Therefore, multidimensional strategies are urgently to find antibacterial dressings to combat bacterial infections. Antibacterial hydrogels are considered potential wound dressing, while their clinical translation is limited due to the unpredictable risks and high costs of carrier excipients. it is found that the natural star antibacterial and anti-inflammatory phytochemicals baicalin (BA) and sanguinarine (SAN) can directly self-assemble through non-covalent bonds such as electrostatic attraction, π–π stacking, and hydrogen bonding to form carrier-free binary small molecule hydrogel. In addition, BA-SAN gel exhibited a synergistic inhibitory effect on MRSA. And its plasticity and injectability allowed it to be applied as a wound dressing. Due to the matched physicochemical properties and synergistic therapeutic effects, BA-SAN gel can inhibit bacterial virulence factors, alleviate wound inflammation, promote wound healing, and has good biocompatibility. The current study not only provided an antibacterial hydrogel with clinical value but also opened up new prospects that carrier-free hydrogels can be designed and originated from clinically used small-molecule phytochemicals.     

Development of nanotechnology for advancement and application in wound healing: a review

Wound healing is a series of different dynamic and complex phenomena. Many studies have been carried out based on the type and severity of wounds. However, to recover wounds faster there are no suitable drugs available, which are highly stable, less expensive as well as has no side effects. Nanomaterials have been proven to be the most promising agent for faster wound healing among all the other wound healing materials. This review briefly discusses the recent developments of wound healing by nanotechnology, their applicability and advantages. Nanomaterials have unique physicochemical, optical, and biological properties. Some of them can be directly applied for wound healing or some of them can be incorporated into scaffolds to create hydrogel matrix or nanocomposites, which promote wound healing through their antimicrobial, as well as selective anti‐ and pro‐inflammatory, and proangiogenic properties. Owing to their high surface area to volume ratio, nanomaterials have not only been used for drug delivery vectors but also can affect wound healing by influencing collagen deposition and realignment and provide approaches for skin tissue regeneration.Inspec keywords: skin, wounds, cellular biophysics, drug delivery systems, tissue engineering, hydrogels, nanocomposites, proteins, nanomedicineOther keywords: wound healing materials, nanomaterials, nanotechnology, proangiogenic properties, proinflammatory properties, collagen deposition, drug delivery vectors, skin tissue regeneration     

Development of novel pH-sensitive nanoparticles loaded hydrogel for transdermal drug delivery

Objective: Difference of pH that exists between the skin surface and blood circulation can be exploited for transdermal delivery of drug molecules by loading drug into pH-sensitive polymer. Eudragit S100 (ES100), a pH-sensitive polymer having dissolution profile above pH 7.4, is used in oral, ocular, vaginal and topical delivery of drug molecules. However, pH-sensitive potential of this polymer has not been explored for transdermal delivery. The aim of this research work was to exploit the pH-sensitive potential of ES100 as a nanocarrier for transdermal delivery of model drug, that is, Piroxicam.

Methods: Simple nanoprecipitation technique was employed to prepare the nanoparticles and response surface quadratic model was applied to get an optimized formulation. The prepared nanoparticles were characterized and loaded into Carbopol 934 based hydrogel. In vitro release, ex vivo permeation and accelerated stability studies were carried out on the prepared formulation.

Results: Particles with an average size of 25–40?nm were obtained with an encapsulation efficiency of 88%. Release studies revealed that nanoparticles remained stable at acidic pH while sustained release with no initial burst effect was observed at pH 7.4 from the hydrogel. Permeation of these nanocarriers from hydrogel matrix showed significant permeation of Piroxicam through mice skin.

Conclusion: It can be concluded that ES100 based pH-sensitive nanoparticles have potential to be delivered through transdermal route.     

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 5: Hydrolytically degradable materials

Macroporous hydrogels based on 2-hydroxyethyl methacrylate, 2-ethoxyethyl methacrylate and N-(2-hydroxypropyl)methacrylamide, methacrylic acid and [2-(methacryloyloxy)ethyl]trimethylammonium chloride crosslinked with N,O-dimethacryloylhydroxylamine were prepared. Hydrogels were degraded in a buffer of pH 7.4. Completely water-soluble polymers were obtained over time periods ranging from 2 to 40 days. The process of degradation was followed gravimetrically and by optical and electron microscopy. In vivo biological tests with hydrogels based on copolymers of 2-ethoxyethyl methacrylate/N-(2-hydroxypropyl)methacrylamide were performed.     

Elastic liposomes-in-vehicle formulations destined for skin therapy: the synergy between type of liposomes and vehicle

Objective: The present study is focused on optimization of elastic liposomes-in-vehicle formulations in respect to drug release and formulation properties. By combining penetration potential of elastic liposomes containing high ratio of entrapped drug and physicochemical properties of vehicles, both affecting the release and texture properties, optimal formulation could be achieved.

Materials and methods: Deformable, propylene glycol-containing or conventional liposomes with hydrophilic model drug (diclofenac sodium) were incorporated into the following vehicles appropriate for skin application: a hydrogel, a cream base and derma membrane structure base cream (DMS base). Each formulation was assessed for in vitro drug release and mechanical properties.

Results and discussion: The composition and type of both liposomes and the vehicle affected the rate and amount of the released drug. The cream base exhibited the slowest release, followed by the hydrogel and DMS base. Similar release profiles were achieved with both types of elastic vesicles (deformable and propylene glycol liposomes); the slowest release was observed for conventional liposomes, regardless of the vehicle used. The drug release profiles from different liposomes-in-vehicle formulations were in agreement with the physicochemical properties of the formulations. All of the liposomes were found to be compatible with the hydrogel preserving its original textures, whereas a significant decrease in all texture parameters was observed for liposomes-in-DMS base, regardless of liposome type.

Conclusion: Propylene glycol liposomes-in-hydrogel is considered as the optimal formulation for improving skin delivery of hydrophilic drug. Further investigations involving in vivo animal studies are necessary to confirm its applicability in skin therapy.