Modified PLGA–PEG–PLGA thermosensitive hydrogels with suitable thermosensitivity and properties for use in a drug delivery system

Wang, Puxiu; Chu, Weifeng; Zhuo, Xuezhi; Zhang, Yu; Gou, Jingxin; Ren, Tianyang; He, Haibing; Yin, Tian; Tang, Xing

doi:10.1039/c6tb02158a

Cited by 87 publications

(39 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At this stage, micellar particles interact and form aggregates leading to the formation of a percolated hydrogel network structure. 12 , 29 , 30 In this study, the PLGA–PEG–PLGA polymers tested exhibited a low critical gelation temperature of approximately 34 °C, providing a flexible transition window for in vivo applications.…”

Section: Resultsmentioning

confidence: 77%

In Situ Forming Injectable Thermoresponsive Hydrogels for Controlled Delivery of Biomacromolecules

et al. 2020

View full text Add to dashboard Cite

Due to their relatively large molecular sizes and delicate nature, biologic drugs such as peptides, proteins, and antibodies often require high and repeated dosing, which can cause undesired side effects and physical discomfort in patients and render many therapies inordinately expensive. To enhance the efficacy of biologic drugs, they could be encapsulated into polymeric hydrogel formulations to preserve their stability and help tune their release in the body to their most favorable profile of action for a given therapy. In this study, a series of injectable, thermoresponsive hydrogel formulations were evaluated as controlled delivery systems for various peptides and proteins, including insulin, Merck proprietary peptides (glucagon-like peptide analogue and modified insulin analogue), bovine serum albumin, and immunoglobulin G. These hydrogels were prepared using concentrated solutions of poly(lactide- co -glycolide)– block -poly(ethylene glycol)– block -poly(lactide- co -glycolide) (PLGA–PEG–PLGA), which can undergo temperature-induced sol–gel transitions and spontaneously solidify into hydrogels near the body temperature, serving as an in situ depot for sustained drug release. The thermoresponsiveness and gelation properties of these triblock copolymers were characterized by dynamic light scattering (DLS) and oscillatory rheology, respectively. The impact of different hydrogel-forming polymers on release kinetics was systematically investigated based on their hydrophobicity (LA/GA ratios), polymer concentrations (20, 25, and 30%), and phase stability. These hydrogels were able to release active peptides and proteins in a controlled manner from 4 to 35 days, depending on the polymer concentration, solubility nature, and molecular sizes of the cargoes. Biophysical studies via size exclusion chromatography (SEC) and circular dichroism (CD) indicated that the encapsulation and release did not adversely affect the protein conformation and stability. Finally, a selected PLGA–PEG–PLGA hydrogel system was further investigated by the encapsulation of a therapeutic glucagon-like peptide analogue and a modified insulin peptide analogue in diabetic mouse and minipig models for studies of glucose-lowering efficacy and pharmacokinetics, where superior sustained peptide release profiles and long-lasting glucose-lowering effects were observed in vivo without any significant tolerability issues compared to peptide solution controls. These results suggest the promise of developing injectable thermoresponsive hydrogel formulations for the tunable release of protein therapeutics to improve patient’s comfort, convenience, and compliance.

show abstract

Section: Resultsmentioning

confidence: 77%

In Situ Forming Injectable Thermoresponsive Hydrogels for Controlled Delivery of Biomacromolecules

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This block copolymer is not approved by FDA, but consists of the FDA approved segments PLGA and PEG individually. This copolymer is widely used as an injectable gel, as it can be injected at low temperatures and is easily converted into a gel in vivo, without the need for surgery [65]. Another synthetic polymer is polycaprolactone (PCL).…”

Section: Synthetic Injectable Hydrogelsmentioning

confidence: 99%

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

Askari

Seyfoori

Amereh

et al. 2020

Gels

View full text Add to dashboard Cite

Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

show abstract

“…7A). 65 Alternatively, triblock hydrophobic-hydrophilic-hydrophobic polymers may achieve gelation by inserting their hydrophobic segments into separate adjacent micelles and connecting them together into a stable hydrogel matrix 44,64,66,67 (Fig. 7B).…”

Section: Effects Of Polymer Branches On Thermogel Propertiesmentioning

confidence: 99%

Supramolecular thermogels from branched PCL-containing polyurethanes

et al. 2020

View full text Add to dashboard Cite

show abstract

Modified PLGA–PEG–PLGA thermosensitive hydrogels with suitable thermosensitivity and properties for use in a drug delivery system

Abstract: PLGA–PEG–PLGA (PPP) triblock copolymer is the most widely studied thermosensitive hydrogel owing to its non-toxic, biocompatible, biodegradable, and thermosensitive properties.

Cited by 87 publications

References 153 publications

In Situ Forming Injectable Thermoresponsive Hydrogels for Controlled Delivery of Biomacromolecules

In Situ Forming Injectable Thermoresponsive Hydrogels for Controlled Delivery of Biomacromolecules

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

Supramolecular thermogels from branched PCL-containing polyurethanes

Contact Info

Product

Resources

About