Biodegradable injectable in situ forming drug delivery systems

Hatefi, Arash; Amsden, Brian G.

doi:10.1016/s0168-3659(02)00008-1

Cited by 646 publications

(425 citation statements)

References 110 publications

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“…Hydrogels are an important class of materials that have been studied extensively in the last decades for the controlled release of pharmaceutical proteins, and for tissue engineering applications [1][2][3][4][5]. Formation of hydrogels can be achieved by both chemical and physical crosslinking [6].…”

Section: Introductionmentioning

confidence: 99%

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Self-gelling hydrogels based on oppositely charged dextran microspheres

et al. 2005

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This paper presents a novel self-gelling hydrogel potentially suitable for controlled drug delivery and tissue engineering. The macroscopic gels are obtained by mixing dispersions of oppositely charged crosslinked dextran microspheres. These microspheres in turn were prepared by crosslinking of dextran derivatized with hydroxyethyl methacrylate emulsified in an aqueous poly(ethylene glycol) solution. Negatively or positively charged microspheres were obtained by addition of methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA) to the polymerization mixture. Rheological analysis showed that instantaneous gelation occurred when equal volumes of oppositely charged microspheres, dispersed in buffer solutions of pH 7, were mixed. The shear modulus of the networks could be tailored from 30 to 6500 Pa by varying the water content of the system. Moreover, controlled strain and creep experiments showed that the formed networks were mainly elastic. Importantly for application of these systems, e.g. as controlled matrix of pharmaceutically active proteins, it was demonstrated that the hydrogel system has a reversible yield point, meaning that above a certain applied stress, the system starts to flow, whereas when the stress is removed, gel formation occurred. Further it was shown that the network structure could be broken by either a low pH or a high ionic strength of the medium. This demonstrates that the networks, formed at pH 7 and at low ionic strength, are held together by ionic interactions between the oppositely charged dextran microspheres. This system holds promise as injectable gels that are suitable for drug delivery and tissue engineering applications. r

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Section: Introductionmentioning

confidence: 99%

“…stereocomplex gels [7][8][9][10]) or after a certain trigger (e.g. temperature [3,[11][12][13][14][15]). Such systems can be administered by injection as liquid formulation and gellify in situ.…”

Section: Introductionmentioning

confidence: 99%

Self-gelling hydrogels based on oppositely charged dextran microspheres

et al. 2005

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“…For example, the PLA/PLGA polymers usually have a glass transition temperature of around 40-608C, 14,15 and therefore are not applicable on their own for injectable drug delivery systems. Injectable polymers themselves are receiving increased attention 16,17 as alternatives to emulsions, liposomes, or microsphere injectable drug delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

Trimaille

Gurny

Möller

2006

J Biomedical Materials Res

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Poly(hexyl-substituted lactides) (PHLA) as new hydrophobic polyesters with controlled molecular weights and narrow distributions were synthesized by ring-opening polymerization (ROP) using tin(II) 2-ethylhexanoate (Sn(Oct) 2 ) and benzyl alcohol as catalyst and initiator. Glass transition temperatures (T g ) and zero shear viscosities (g 0 ) at 258C could be modulated from T g ¼ À428C to À108C and 40 to 4850 Pa s, respectively, by varying the polymer molecular weight and the number of hexyl groups along the polymer chain. Degradation studies were performed in terms of both mass and molecular weight loss in the course of time. The degradation mechanism is shown to be of the ''bulk erosion'' type, and comparable to standard poly(D,L-lactide) (PLA). Despite the increased steric hindrance in the poly(monohexyl-substituted lactide) (PmHLA) due to the hexyl side groups, its degradation rate at pH 7.4 and 378C was found to be slightly higher than observed for the analogue standard PLA. This could be attributed to the flexible rubbery state of the hexyl-substituted polymer (T g *À158C) at the physiological temperature, which is favoring the degradation in comparison to the rigid and glassy standard PLA (T g *408C). In contrast, degradation studies performed at 608C, where both polymers are above their glass transition temperature, confirmed that the degradation rate is lower for the sterically more hindered PmHLA. The degradation products were analyzed by ESI-MS. Hydrolysis lead first to the corresponding oligo-ester fragments and finally to the nontoxic 2-hydroxyoctanoic acid and lactic acid. Tetracycline was tested as a model drug for release studies. This drug was found to be released faster and in higher amounts in its active form from the PHLA matrix than from standard PLA. The results presented in this work demonstrate the potential of these hydrophobic polylactide-based semisolid materials as an alternative to conventional PLA/PLGA for injectable drug delivery systems. 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A: [55][56][57][58][59][60][61][62][63][64][65] 2007

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“…Depending on the monomers used, the resulting microgels may be sensitive to external stimuli, such as temperature, pH, and ionic strength of the aqueous solution. [9,10] The stimulisensitive gels based on copolymers, have been intensively studied and significant progress has been achieved in recent years. Temperature is one of the most widely used stimuli for stimuli-sensitive gels, because it is easy to control and has practical advantages in both in vitro and in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

Temperature-responsive poly(N-vinylcaprolactam-co-hydroxyethyl methacrylate) nanogels for controlled release studies of curcumin

Sudhakar

Rao

Subha

et al. 2015

Designed Monomers and Polymers

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(2015) Temperature-responsive poly(N-vinylcaprolactam-co-hydroxyethyl methacrylate) nanogels for controlled release studies of curcumin, Designed Monomers and Polymers, 18:8, 705-713, DOI: 10.1080/15685551.2015 A series of nanogels (NGs) were developed from N-vinylcaprolactam and hydroxyethyl methacrylate through free radical emulsion polymerization using methylene bis acrylamide as cross-linker. Curcumin, an anticancer agent was successfully loaded into these NGs via equilibrium in situ method. These NGs were characterized by Fourier transform spectroscopy (FTIR), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and dynamic light-scattering experimental (DLS) techniques. The formation of co-polymeric NGs was confirmed by FTIR analysis. DSC results reveal that the drug was molecularly dispersed in the NG networks. TEM results indicate the formation of NGs, in a spherical shape, with the size of 150 nm. The DLS results also support the formation and size of NGs. An in vitro release study indicates that the NGs may be potentially useful for targeted drug delivery applications.

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Biodegradable injectable in situ forming drug delivery systems

Cited by 646 publications

References 110 publications

Self-gelling hydrogels based on oppositely charged dextran microspheres

Self-gelling hydrogels based on oppositely charged dextran microspheres

Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

Temperature-responsive poly(N-vinylcaprolactam-co-hydroxyethyl methacrylate) nanogels for controlled release studies of curcumin

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