Objective Supramolecular hydrogels were the hydrogels consisting of a solid 3D network with noncovalent bonds.Its unique properties such as biocompatibility,biodegradability,free sol-gel transformation and stable drug release ability make it widely exploited for various biomedical applications.This paper mainly focused on the use of supramolecular hydrogels in all types of biomedical application such as biosensor,cell culture,tissue engineering,gene engineering and drug delivery by research literature reviews.They hope that this focus review will contribute topromote the use of supramolecular hydrogels.
Key words:
Supramolecular hydrogels
;
Biomedical application
;
Drug delivery
超分子凝胶(supramolecular hydrogels)是一种由氢键、疏水作用、π-π相互作用等非共价键形成的三维网状水凝胶。超分子凝胶为物理交联凝胶,有很多传统化学交联凝胶不具备的优势,如良好的生物相容性、生物可降解性、凝-融胶互变特性以及良好的载药特性,对药物还具有稳定、长效、可控的释放特性。近年来,有关超分子凝胶的研究受到广泛关注。在SciFinder®上检索“supramolecular hydrogels”(超分子凝胶),包含该检索词的文献有1 656篇。检索“supramolecular hydrogels in drug delivery”(超分子凝胶在给药系统中的应用),与其紧密关联的文献有172篇,其中2010年以后发表125篇,占总量的73%。在中国知网全文检索“超分子凝胶”,有相关文献19 771篇。超分子凝胶已经成为一个蓬勃发展的研究领域。笔者通过整理文献资料,综述超分子凝胶在生物医药领域的研究应用和进展。
TAMARU SI,KIYONAKAS,HAMACHII.Three distinct read-out modes for enzyme activity can operate in a semi-wet supramolecular hydrogel[J].Chem Eur J,2005,11(24):7294-7304.
Assays of hydrolytic enzyme activity, such as of glycosidases and phosphatase, as well as several proteases, using a semi-wet supramolecular hydrogel array composed of a glycosylated amino acetate are described. It has been demonstrated that the microcavity formed by gel fibrils is suitable to immobilize native enzymes without denaturation under semi-wet conditions, and thus the nanofiber has been rationally used as a sensing domain to monitor enzymatic reactions. By using a fluorogenic substrate, reducing the size of the hydrogel can significantly improve the problem of suppressed diffusion within the gel matrix thus making the hydrogel a promising semi-wet matrix for evaluating enzyme activity. Confocal laser scanning microscopy observations have shown that an environmentally sensitive fluorescent probe accumulates in the hydrophobic domain of the gel fiber and emits fluorescence more strongly upon hydrolytic cleavage of the substrate peptides. Not only a simple environmentally sensitive probe but also a FRET (fluorescence resonance energy transfer)-type read-out mode can be devised to analyze the enzymatic hydrolysis-triggered redistribution of the probe between the nanospace and the nanofiber to accomplish a more clearly distinguished enzyme assay. Thus, it is clear that three distinct read-out modes, that is, 1) fluorogenic substrates, 2) substrates bearing an environmentally sensitive probe, or 3) a substrate exhibiting FRET, can operate under the semi-wet hydrogel conditions used in these investigations. In addition, owing to the unique properties of the present supramolecular hydrogel in semi-wet conditions, that is, its phase-segregation properties and dynamics, the supramolecular substrate/enzyme array has successfully been used for high-throughput screening of single and multiple enzymes based on their activity, lysate analysis, and quantitative evaluation of inhibitor potency and selectivity.
LIJ,LI HM,YANG XY,et al.The supramolecular hydrogel based on hyperbranch edpolyglycerol and dextran as a scaffold for living cells and drug delivery[J].RSC Adv,2015,5(105):86730-86739.
[本文引用:1]
[3]
TRAN NQ,JOUNG YK,LIHE,et al.RGD-conjugated in situ forming hydrogels as cell-adhesive injectable scaffolds[J].Macromol Res,2011,19(3):300-306.
In this study, a bioactive hydrogel was prepared from a chitosan derivative and Arg -Gly-Asp (RGD)-conjugated polypseudorotaxane, which is a cell-adhesive extracellular matrix. Chitosan was modified with 4-hydroxy phenyl acetic acid to obtain a water-soluble product for enzymatic cross-linking. Tyramine-terminated polypseudorotaxane (PRx) was prepared from the inclusion complex of a tyramine-terminated poly(ethylene glycol) backbone, and -cyclodextrin ( -CD). Gly- Arg -Gly-Asp-Ser (GRGDS) was conjugated to the PRx using 4-nitrophenyl chloroformate (NPC) and partially carboxylated with succinic anhydride. The structure of the PRx-RGD and 4-hydroxylphenylacetamide chitosan (CHPA) was characterized by 1 H NMR and FTIR spectroscopy. The RGD content in PRx-RGD was determined to be 0.19%. PRx-RGD and CHPA solution was crosslinked to form a bioactive hydrogel in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ), which exhibited rapid gelation ( 20 sec). An in vitro cell culture was carried out with L929 mouse fibroblasts for 1 and 3 days. The results showed that fibroblasts adhered better and appeared to be more biocompatible on the RGD-conjugated hydrogel than the hydrogel without RGD. The combined results highlight the potential use of this bioactive hydrogel as an injectable scaffold in tissue engineering applications.
WANG WJ,WANG H A M,REN C H,et al.A saccharide-based supramolecular hydrogel for cell culture[J].Carbohyd Res,2011,346(8):1013-1017.
It is well known that the saccharides forming the intricate sugar coat that surrounds the cells play important biological roles in intercellular communication and cell differentiation. Therefore, it is worthwhile developing saccharide-based hydrogels for cell culture study. In this study, three novel saccharide-based compounds were designed and synthesized. It was found that one of them could form hydrogels efficiently, while the other two precipitated from water. The stability of the resulting hydrogel was tested, and the supramolecular nanofiber with fiber diameters in the range of 80–30002nm was characterized as the structural element by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fluorescence microscopy revealed that extensive hydrogen bonds between sugar rings assisted the formation of efficient π–π stacking between aromatic naphthalene groups, thus resulting in the formation of a stable hydrogel in aqueous solution. When the gel was applied for mouse embryonic fibroblast (NIH 3T3), human hepatocellular carcinoma (HepG2), AD293 and HeLa cells culture in two dimensional environments, all of them showed a very good adhesion and good proliferation rate on the top of the hydrogel. These results indicates that the biocompatible hydrogel reported here has a potential to be developed into useful materials for in vitro cell culture, drug delivery, and tissue engineering.
HU YH,WANG H A M,WANG J Y,et al.Supramolecular hydrogels inspired by collagen for tissue engineering[J].Org Biomol Chem,2010,8(14):3267-3271.
Supramolecular hydrogels are promising biomaterials for cell culture in 2-D and 3-D environments. Inspired by the chemical structure of collagen, which bears the repeating tripeptide of glycine-Xaa-4R-hydroxyproline (GXO; Xaa is any one of the natural amino acids), we designed and synthesized a small library of supramolecular hydrogelators (a total of 6). We found that four of the hydrogels were suitable for NIH 3T3 cell culture in the 2-D environments. Gel 2, the best hydrogel, has properties that are similar to those of collagen for 3T3 cell culture. These findings not only provide more supramolecular hydrogel candidates for tissue engineering, but also offer a new strategy for designing biomaterials that mimic nature.
CUI HT,CUI LG,ZHANG PB,et al.In situ electroactive and antioxidant supramolecular hydrogel based on cyclodextrin/copolymer inclusion for tissue engineering repair[J].Macromol Biosci,2014,14(3):440-450.
The injectable electroactive and antioxidant hydrogels are prepared from mixing the tetraaniline functional copolymers and -cyclodextrin (伪-CD) aqueous solution. UV-vis and CV of the copolymer solution showed good electroactive properties. The antioxidant ability of the copolymer is also proved. The gelation mechanism and properties of the system are studied by WAXD, DSC, and rheometer. The encapsulated cells are highly viable in the hydrogels, suggesting that the hydrogels have excellent cytocompatibility. After subcutaneous injection, H&E staining study suggests acceptable biocompatibility of the materials in vivo. Moreover, data shows the injectable electroactive material can effectively accelerate the proliferation of encapsulated cells with electrical stimuli, and the mechanism is also elaborated. Such an injectable electroactive hydrogel would more closely mimic the native extracellular matrix, thereby combining a biomimetic environment of long-term cell survival and electrical signal to support the generation of functional tissue.
JUNGH,PARK JS,YEOMJ,et al.3D tissue engineered supramolecular hydrogels for controlled chondrogenesis of human mesenchymal stem cells[J].Biomacromolecules,2014,15(3):707-714.
Despite a wide investigation of hydrogels as an artificial extracellular matrix, there are few scaffold systems for the facile spatiotemporal control of mesenchymal stem cells (MSCs). Here, we report 3D tissue engineered supramolecular hydrogels prepared with highly water-soluble monofunctionalized cucurbit[6]uril-hyaluronic acid (CB[6]-HA), diaminohexane conjugated HA (DAH-HA), and drug conjugated CB[6] (drug-CB[6]) for the controlled chondrogenesis of human mesenchymal stem cells (hMSCs). The mechanical property of supramolecular HA hydrogels was modulated by changing the cross-linking density for the spatial control of hMSCs. In addition, the differentiation of hMSCs was temporally controlled by changing the release profiles of transforming growth factor- 3 (TGF- 3) and/or dexamethasone (Dexa) from the hydrolyzable Dexa-CB[6]. The effective chondrogenic differentiation of hMSCs encapsulated in the monoCB[6]/DAH-HA hydrogel with TGF- 3 and Dexa-CB[6] was confirmed by biochemical glycosaminoglycan content analysis, real-time quantitative PCR, histological, and immunohistochemical analyses. Taken together, we could confirm the feasibility of cytocompatible monoCB[6]/DAH-HA hydrogels as a platform scaffold with controlled drug delivery for cartilage regeneration and other various tissue engineering applications.
LI JB,KOOGERR,HE MT,et al.A supramolecular hydrogel as a carrier to deliver microRNA into the encapsulated cells[J].Chem Commun,2014,50(28):3722-3724.
A supramolecular hydrogel formed by dipeptide Gly-Ala linked with biphenyl-substituted tetrazole serves not only as a 3D matrix for live cells, but also as a carrier to deliver microRNA into the encapsulated cells.
MAD,ZHANG HB,CHEN DH,et al.Novel supramolecular gelation route to in situ entrapment and sustained delivery of plasmid DNA[J].Colloid Interface Sci,2011,364(2):566-573.
In this work, cationic block copolymer (F-68-PLL) composed of Pluronic F-68 and poly( l -lysine) segments was first prepared for the binding with plasmid DNA due to the electrostatic interaction between poly( l -lysine) segments and plasmid DNA, and subsequently used to interact with α-cyclodextrin (α-CD) in aqueous system for the supramolecular gelation by the inclusion complexation between Pluronic F-68 segments and α-CD. It was found that such a fabrication process could lead to the in situ entrapment of plasmid DNA into the supramolecular hydrogel matrix under mild conditions. Depending on the amounts of F-68-PLL and α-CD, the resultant hybrid hydrogel was found to have adjustable gelation time and mechanical strength. For the plasmid DNA complexes released from the supramolecular hydrogel, controlled release and sustained gene transfection were confirmed.
YANG ZM,XU KM,WANGL,et al.Self-assembly of small molecules affords multifunctional supramolecular hydrogels for topically treating simulated uranium wounds[J].Chem Commun,2005,(35):4414-4416.
Two types of therapeutic agents, which have discrete yet complementary functions, self-assemble into nanofibers in water to formulate a new supramolecular hydrogel as a self-delivery biomaterial to reduce the toxicity of uranyl oxide at the wound sites.
XU KM,GE WW,LIANG GL,et al.Bisphosphonate-containing supramolecular hydrogels for topical decorporation of uranium-contaminated wounds in mice[J].Int J Radiat Biol,2008,84(5):353-362.
Personnel experiencing accidents that involve radionuclides or victims of potential malicious radioactive attacks may suffer injuries with wounds contaminated by radionuclides. The current treatment for contamination from uranium in external injuries is the use of saline solution to wash the wounds, which has the drawback of further spreading of the contaminants due to the flow of water. To minimize the cost of storage of contaminated liquids and to improve the efficiency of treatment, we propose the use of hydrogels as a form of decorporation agent. Mice with uranium-contaminated wounds on their backs were treated with bisphosphonate or diethylene triamine pentaacetic acid (DTPA) containing supramolecular hydrogels. Survival rates of the treated mice and changes in the body weight of the mice were observed and compared to those of mice without hydrogel treatment. Distribution of uranium in the mice was also explored as proof of the effectiveness of the hydrogel treatment. The survival rate of the hydrogel-treated mice was significantly higher than that of the mice without treatment. The body weights of the hydrogel-treated mice showed significant recovery after 10 days while the body weight of mice without hydrogel treatment continuously decreased. The amount of uranyl ions in the organs (mainly concentrated in the kidney) of the hydrogel-treated mice was much smaller than that of the mice without hydrogel treatment. By incorporating uranium chelating agents, we developed new supramolecular hydrogels that could effectively and conveniently decorporate uranium ions from the contaminated wound sites of mice, with the highest efficacy achieved by our pamidronate-based molecular hydrogel.
YANGZ,LIANGG,MAM,et al.D-glucosamine-based supramolecular hydrogels to improve wound healing[J].Chem Commun,2007,8(8):843-845.
Abstract A simple supramolecular hydrogel based on D-glucosamine, a naturally occurring aminosaccharide, promises new biomaterials for applications such as wound healing.
LEE A LZ,VENKATARAMANS,FOX CH,et al.Modular composite hydrogels from cholesterol-functionalized polycarbonates for antimicrobial applications[J].J Mater Chem B,2015,3(34):6953-6963.
Micellar composite hydrogel systems represent a promising class of materials for biomolecule and drug delivery applications. In this work a system combining micellar drug delivery with supramolecular hydrogel assemblies is developed, representing an elegant marriage of aqueous hydrophobic drug delivery and next-generation injectable viscoelastic materials. Novel shear thinning and injectable micellar composite hydrogels were prepared using an amphiphilic ABA-type triblock copolymer consisting of a hydrophilic middle block and cholesterol-functionalized polycarbonates as terminal hydrophobic blocks. Varying the concentration and relative hydrophobic ydrophilic content of the amphiphilic species conferred the ability to tune the storage moduli of these gels from 200 Pa to 3500 Pa. This tunable system was used to encapsulate drug-loaded polymeric micelles, demonstrating a straightforward and modular approach to developing micellar viscoelastic materials for a variety of applications such as delivery of hydrophobic drugs. These hydrogels were also mixed with cholesterol-containing cationic polycarbonates to render antimicrobial activity and capability for anionic drug delivery. Additionally, small-angle X-ray scattering (SAXS) and electron microscopy (EM) results probed the mesoscale structure of these micellar composite materials, lending molecular level insight into the self-assembly properties of these gels. The antimicrobial composite hydrogels demonstrated strong microbicidal activity against Gram-negative and Gram-positive bacteria, andC. albicansfungus. Amphotericin B (AmB, an antifungal drug)-loaded micelles embedded within the hydrogel demonstrated sustained drug release over 4 days and effective eradication of fungi. Our findings demonstrate that materials of different nature (i.e.small molecule drugs or charged macromolecules) can be physically combined with ABA-type triblock copolymer gelators to form hydrogels for potential pharmaceutical applications.
IBRAHIM MM,ABDELAGAWAD AH,SOLIMAN OA,et al.Novel topical ophthalmic formulations for management of glaucoma[J].Pharm Res,2013,30(11):2818-2831.
Abstract PURPOSE: Preparation of topical ophthalmic formulations containing brimonidine-loaded nanoparticles prepared from various biodegradable polymers-PCL, PLA and PLGA-for sustained release of brimonidine as a once daily regimen for management of glaucoma. METHODS: Nanoparticles were prepared using spontaneous emulsification solvent diffusion method then characterized regarding their particle size, zeta potential, morphology and drug contents. Brimonidine-loaded nanoparticles were incorporated into eye drops, temperature-triggered in situ gelling system and preformed gel and characterized regarding their pH, viscosity, uniformity of drug contents, in vitro release study, in vitro cytotoxicity and in vivo intraocular pressure (IOP) lowering effects. RESULTS: The results of optimized brimonidine-loaded PCL-, PLGA- and PLA-NPs respectively, are: particle sizes of 117.3365±654.5802nm, 125.6765±655.1502nm and 131.6765±653.7902nm; zeta potentials of -18.565±652.8702mV, -21.8265±652.702mV and -28.1165±652.2102mV; and encapsulation efficiencies of 77.9765±651.38%, 68.6565±653.35% and 73.5265±652.92%. TEM analyses revealed that all NPs have spherical shapes with dense core and distinct coat. In vitro release data showed a sustained release without any burst effect with Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are non-toxic. Also all formulations possessed a sustained IOP lowering effect compared to Alphagan03 P eye drops. CONCLUSIONS: Our formulations showed prolonged management of glaucoma that should meet with better patient compliance as a once-daily formulation.
ABDELKADERH,ALANY RG.Controlled and continuous release ocular drug delivery systems:pros and cons[J].Curr Drug Deliv,2012,9(4):421-430.
Abstract Topical ocular drug administration is the most preferred route for treating conditions affecting the surface of the eye as well as anterior segment diseases; this is mainly due to the rapid and localised drug action and patient acceptability. However, the ocular bioavailability is typically less than 5% from conventional ophthalmic dosage forms such as eye drops. This is mainly due to the unique anatomical and physiological features of the eye. One of the effective pharmaceutical approaches is to provide a controlled and continuous drug release to the surface of the eye to compensate drug loss by nasolacrimal drainage and non-productive absorption of the topically applied drug. This review provides a critical appraisal (advantages and drawbacks) of the different drug delivery strategies that provides controlled and continuous drug supply to the surface of the eye; it covers research conducted over the past three decades.
KOMPELLA UB,KADAM RS,LEE V H L.Recent advances in ophthalmic drug delivery[J].Ther Deliv,2010,1(3):435-456.
Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert64 (656 months), Retisert64 (653 years) and Iluvien64 (653 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems.
GANL,WANGJ,LIANGM,et al.Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers[J].Drug Discov Today,2013,18(5-6):290-297.
Ocular barriers and the poor water solubility of drug candidates present a number of problems for the development of ocular drug delivery systems. Recently, the emergence of lipid-based nanocarriers has provided a viable means of enhancing the bioavailability of ophthalmic formulations. A number of these formulations have been found to be clinically active and several others are currently undergoing clinical trials. In this review, the advantages of lipid-based nanocarriers as non-invasive topical ocular drug delivery systems are presented. Many systems, including emulsions, liposomes, cubosomes, niosomes and other lipid-based nanocarriers, are reviewed.
SOUZA JG,DIASK,PEREIRA TA,et al.Topical delivery of ocular therapeutics:carrier systems and physical methods[J].J Pharm Pharmacol,2014,66(4):507-530.
Abstract Top of page Abstract Introduction Delivery systems Physical methods Summary and perspectives Declarations References Objective The basic concepts, major mechanisms, technological developments and advantages of the topical application of lipid-based systems (microemulsions, nanoemulsions, liposomes and solid lipid nanoparticles), polymeric systems (hydrogels, contact lenses, polymeric nanoparticles and dendrimers) and physical methods (iontophoresis and sonophoresis) will be reviewed. Key findings Although very convenient for patients, topical administration of conventional drug formulations for the treatment of eye diseases requires high drug doses, frequent administration and rarely provides high drug bioavailability. Thus, strategies to improve the efficacy of topical treatments have been extensively investigated. In general, the majority of the successful delivery systems are present on the ocular surface over an extended period of time, and these systems typically improve drug bioavailability in the anterior chamber whereas the physical methods facilitate drug penetration over a very short period of time through ocular barriers, such as the cornea and sclera. Summary Although in the early stages, the combination of these delivery systems with physical methods would appear to be a promising tool to decrease the dose and frequency of administration; thereby, patient compliance and treatment efficacy will be improved.
ZHANGZ,HEZ,LIANGR,et al.Fabrication of a micellar supramolecular hydrogel for ocular drug delivery[J].Biomacromolecules,2016,17(3):798-807.
In this paper, we describe a simple method for constructing a micellar supramolecular hydrogel, composed of a low-molecular-weight methoxy poly(ethylene glycol) (Mn = 2000 Da) block polymer and α-cyclodextrin (α-CD), for topical ocular drug delivery. Adding aqueous block polymer micelles into an α-CD aqueous solution resulted in the formation of a micellar supramolecular hydrogel through host–guest inclusion. The effects of the drug payload, block polymer, and α-CD concentrations as well as the block polymer structure on gelation time were investigated. The resultant micellar supramolecular hydrogels were thoroughly characterized by X-ray diffraction, rheological studies, and scanning electron microscopy. The hydrogels exhibited thixotropic properties, which are beneficial to ocular drug delivery. In vitro release studies indicated that the α-CD concentration strongly influenced the release rate of diclofenac (DIC) from supramolecular hydrogel. The hydrogels showed relatively low cytotoxicity toward L-929...
LI XY,WANG YQ,YANG CB,et al.Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy[J].Nanoscale,2014,6(23):14488-14494.
Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular compatibility in rats, as indicated by the optical coherence tomography (OCT) images, HE observation, and glial fibrillary acidic protein (GFAP) and vimentin immuno-staining assays of the retinas. Our TA hydrogel showed a decreased efficacy to inhibit ocular inflammation in the rat's experiment autoimmune uveitis (EAU) model compared to the commercial TA suspension (Transton), but without causing complications such as high intraocular pressure and cataracts. These promising properties of the hydrogel indicated its great potential for the treatment of eye diseases.
DANKERS P YW,VANLUYN M JA,VLAG A H V D,et al.Convenient formulation and application of a supramolecularu reido-pyrimidinone modified poly(ethylene glycol) carrier for intrarenal growth factor delivery[J].Eur Polym,2015,72:484-493.
The development of local, intrarenal drug delivery therapies is imperative to induce a therapeutic effect without the requirement of high concentrations of drugs, thereby diminishing systemic side effects. Hydrogels are eminently suitable as drug delivery carriers in soft tissues. Here, we show that a supramolecular hydrogel carrier based on ureido-pyrimidinone (UPy) modified poly(ethylene glycol) can be easily formulated and conveniently be applied to deliver anti-inflammatory and anti-fibrotic growth factor protein BMP7 to the kidney. Short-term, immediate modulation of renal inflammation and extracellular matrix remodelling is shown in a rat model of acute kidney injury. Induction of ischemia/reperfusion injury was followed by renal subcapsular implantation of pristine and BMP7-loaded supramolecular hydrogels. The cortical area under the site of implantation was studied after 3 and 7 days. Subcapsular delivery of only 0.30 g BMP7 from these supramolecular hydrogels led to a significant reduction in interstitial inflammatory and myofibroblast cell numbers at the site of implantation. These findings show that local, intrarenal delivery of an anti-inflammatory and anti-fibrotic drug from a supramolecular hydrogel carrier can be effective in the reduction of acute inflammation and incipient fibrosis.
LI RX,SHUC,WANGW,et al.Encapsulation of 10-hydroxy camptothecin in supramolecular hydrogel as an injectable drug delivery system[J].Pharm Sci,2015,104(7):2266-2275.
10-Hydroxy camptothecin (HCPT) has been proven to be a cell cycle-specific chemotherapeutic agent, which is a necessary choice to inhibit tumor residue growth and prevent tumor metastasis after surgery. But it suffers from light decomposition, poor solubility, relatively low bioavailability, and some side effects, which are the major obstacles toward its clinical use. Integration of hydrophobic HCPT with hydrophilic hydrogel is a facile approach to change the disadvantageous situation of HCPT. In this study, a novel supramolecular hydrogelator with improved synthetic strategy was triggered by chemical hydrolysis, and then self-assembled to hydrogel. Taking advantage of the high-equilibrium solubility of HCPT in hydrogelator solution, this hydrogel was utilized to load HCPT via encapsulation as an effective carrier. HCPT hydrogels were characterized by several techniques including transmission electronic microscopy, rheology, and UV spectroscopy.In vitrorelease experiment indicated HCPT hydrogel could maintain long term and sustained release of HCPT at high accumulated rate. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that HCPT hydrogel had an optimized anticancer efficacy. Besides, with prominent physical properties of carrier, HCPT hydrogel possessed satisfactory stability, syringeability, and recoverability, demonstrating itself as a potential localized injectable drug delivery system. 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2266 2275, 2015
WANGT,JIANG XJ,LINT,et al.The inhibition of postinfarct ventricle remodeling without polycythaemia following local sustained intramyocardial delivery of erythropoietin within a supramolecular hydrogel[J].Biomaterials,2009,30(25):4161-4167.
Erythropoietin (EPO) can protect myocardium from ischemic injury, but it also plays an important role in promoting polycythaemia, the potential for thrombo-embolic complications. Local sustained delivery of bioactive agents directly to impaired tissues using biomaterials is an approach to limit systemic toxicity and improve the efficacy of therapies. The present study was performed to investigate whether local intramyocardial injection of EPO with hydrogel could enhance cardioprotective effect without causing polycythaemia after myocardial infarction (MI). To test the hypothesis, phosphate buffered solution (PBS), α-cyclodextrin/MPEG–PCL–MPEG hydrogel, recombined human erythropoietin (rhEPO) in PBS, or rhEPO in hydrogel were injected into the infarcted area immediately after MI in rats. The hydrogel allowed a sustained release of EPO, which inhibited cell apoptosis and increased neovasculature formation, and subsequently reduced infarct size and improved cardiac function compared with other groups. Notably, there was no evidence of polycythaemia from this therapy, with no differences in erythrocyte count and hematocrit compared with the animals received PBS or hydrogel blank injection. In conclusion, intramyocardial delivery of rhEPO with α-cyclodextrin/MPEG–PCL–MPEG hydrogel may lead to cardiac performance improvement after MI without apparent adverse effect.
Convenient formulation and application of a supramolecularu reido-pyrimidinone modified poly(ethylene glycol) carrier for intrarenal growth factor delivery
The inhibition of postinfarct ventricle remodeling without polycythaemia following local sustained intramyocardial delivery of erythropoietin within a supramolecular hydrogel
, 贡雪芃, 郭霞, 孙源源, 杜光
