Category Archives: Thermogels/Temperature Sensitive

Category is for the discussion of polymers which either gel upon heating (thermogel) or display a temperature sensitive property.

Thermogelling PLGA-PEG-PLGA from PolySciTech used for delivery of paclitaxel, rapamycin, and LS301 as part of ovarian cancer theranostic research.

PolySciTech division of Akina, Inc. ( provides a wide array of biodegradable block copolymers including thermogels such as PLGA-PEG-PLGA. One of the uses for this type of polymer is to provide for injectable delivery of medicines. Because the polymer gels and entraps the pharmaceuticals inside, it allows for localized delivery of the drug over a period of time. Recently, researchers have utilized this polymer to create a co-formulation with three chemotherapeutic and theranostic agents (paclitaxel, rapamycin, and LS301). They injected this in a mouse model and tracked its effect against ovarian cancer cells. Read more: McKenzie, Matthew, David Betts, Amy Suh, Kathryn Bui, Rui Tang, Kexian Liang, Samuel Achilefu, Glen S. Kwon, and Hyunah Cho. “Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer.” Pharmaceutical Research (2016): 1-9.

“Abstract: Purpose: The purpose of this study is to investigate a sol–gel transition property and content release profiles for thermosensitive poly-(D,L-lactide-co-glycolide)-block-poly-(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) hydrogels carrying paclitaxel, rapamycin, and LS301, and to present a proof-of-concept that PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, called TheranoGel, exhibit excellent theranostic activity in peritoneal ES-2-luc ovarian cancer xenograft mice. Methods: Thermosensitive PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, individually or in combination, were prepared via a lyophilization method, characterized with content release kinetics, and assessed with theranostic activity in ES-2-luc xenograft mice. Results: A thermosensitive PLGA-b-PEG-b-PLGA sol–gel system was able to entrain 3 poorly water-soluble payloads, paclitaxel, rapamycin, and LS301 (TheranoGel). TheranoGel made a sol-to-gel transition at 37°C and slowly released 3 drugs at a simultaneous release rate in response to the physical dissociation of hydrogels in vitro. TheranoGel enabled loco-regional delivery of multi-drugs by forming a gel-depot in the peritoneal cavity of ES-2-luc xenograft mice. An intraperitoneal (IP) administration of TheranoGel resulted in excellent therapeutic and diagnostic activities, leading to the improved peritoneal surgery in ES-2-luc xenograft mice. Conclusions: TheranoGel prepared via a facile lyophiliation method enabled successful IP delivery of multi-drugs and exhibited excellent theranostic activity in vivo. KEY WORDS: hydrogels intraperitoneal ovarian cancer theranostics thermosensitive”

Use of Tumor Spheroids for preclinical cancer studies

Akina, Inc. provides several research products including thermogelling scaffold for 3D culture of cells under the trade-name 3DCellMaker ( One of the applications of this system is the 3D culture of tumor cells. This is a critical and needed technology especially as one major bottle-neck for development of cancer therapeutics is the lack of a biorelevant bench-top test. For this reason, many proposed cancer therapies progress on and fail at a later state in clinical testing where the cost to human health as well as financial loss is immense. Read more about 3D culture of tumor cells in a very well written review article here: Zhang, Weijie, Ai Zhuang, Ping Gu, Huifang Zhou, and Xianqun Fan. “A Review of the Three-Dimensional Cell Culture Technique: Approaches, Advantages and Applications.” Current stem cell research & therapy 11, no. 4 (2016): 370-380.

Abstract: Cell culture is a core and basic technique in biotechnology and is widely applied in biology, medicine, drug research and development. Traditional two-dimensional cell culture methods have undergone great developments. However, with in-depth basic research, higher requirements are needed to better mimic the in vivo environment to accurately observe cell behavior and explore its mechanisms. To comply with this situation, the three-dimensional cell culture technique emerged and has made profound advances in sustaining inherent cell properties. Here, we briefly review the development of this technique, including the main approaches to form three-dimensional microtissues, and its application and potential for future clinical therapies. Keywords: Advantages; applications; scaffold; scaffold-free methods; three-dimensional cell culture”

Recent publication details usage of mixed PolySciTech PLGA-PEG-PLGA and its biocompatibility

PolySciTech division of Akina, Inc. ( provides a wide array of biodegradable block copolymers including thermogelling PLGA-PEG-PLGA. This system, designed to provide for a liquid solution at room temperature and a gel at body temperature, can be used for a wide degree of applications such as depot drug delivery. Recently, researchers at Marshall University and the Huntington Veterans Affairs Medical Center, performed a series of experiments using PolySciTech PLGA-PEG-PLGA’s PolyVivo AK012 and AK019. These two products have transition temperatures slightly below and above body temperature, respectively, however the blending of them together allows for tuning the transition temperature. The researchers performed a series of placebo controlled experiments in rats investigating for any systemic signs of toxicity over the course of 21 days. They found no statistically significant changes in body weight, blood protein ratios, organ weights, Bilirubin, ALT, or other indicators of overall health indicating that these polymers are safe and non-toxic. Read more: Cuifen Wang, Eric Blough, Ravikumar Arvapalli, Omolola Olajide, Henry Driscoll, Maali Milhem, Shahed Elhamdani, Nicole Winston, William E. Triest , and Miaozong Wu. “AK12/AK19 PLGA-PEG-PLGA Triblock Polymer: Thermo-Gelation Properties and in vivo Biocompatibility”. Jacobs Journal of Molecular and Translational Medicine January 2016 Volume 2 Issue 1

“Abstract: This study was to determine a novel and applicable PLGA-PEG-PLGA triblock copolymer with ideal gelation at the physiological temperature. A maximum gelation at 37 °C was obtained by mixing two polymers at 1:3 ratio, PLGA1000-PEG1000- PLGA1000(named as AK12) and PLGA1500-PEG1500-PLGA1500 (AK19). The AK12/AK19 polymer rapidly initiated gelation when temperature was greater than 32°C and had a single gelation peak at ~37°C. Placebo-controlled animal study showed intraperitoneal administration of AK12/AK19 copolymer (20%w/v) did not affect body weight, food and water consumption during 21-day study. Similarly, blood biochemical analysis showed no difference of organ weight, indices of overall health, liver and kidney functions between the polymer and placebo groups. Taken together, these data suggest that the AK12/AK19 PLGA-PEG-PLGA copolymer exhibits desirable thermoregulable and biocompatible properties, which allow in vitro preparation at cool or room temperatures but ideal gelation after in vivo delivery, and may make it extremely attractive for drug delivery applications. Keywords: PLGA-PEG-PLGA Copolymer; AK12; AK19; Thermo-gelation; Biocompatibility; Rheology; in vivo study”

PLGA-PEG-PLGA investigated for intratympanic delivery of antiviral medicines as cytomegalovirus treatment

PolySciTech division of Akina, Inc ( provides a wide array of biodegradable block copolymers including PLGA-PEG-PLGA. This biodegradable thermogel is a free-flowing solution at room temperature and stiffens to a gel when warmd to body temperature. One common cause of hearing loss is a cytomegalovirus (CMV) which is a viral infection that leads to progressive deterioration of the inner ear and eventual hearing loss in children. The two most common antivirals used to treat this (Ganciclovir and Cidofovir) are effective against the virus but have significant toxicity when delivered systemically especially towards kidneys. One way to avoid system side effects is to provide for a localized delivery of the medicine to the exact location needed so that overall systemic dose is very low while the local dose is about the therapeutic threshhold. Recently, researchers in Cincinnati have combined these antivirals with thermogelling PLGA-PEG-PLGA along with anti-inflammatory dexamethasone to generate a system that can be injected into the intratympanic space and deliver these medicines there. This research may be useful for treating a disease which leads to hearing loss in the future. Read more: Sidell, Douglas, Jonette A. Ward, Angad Pordal, Carson Quimby, Michel Nassar, and Daniel I. Choo. “Combination therapies using an intratympanic polymer gel delivery system in the guinea pig animal model: A safety study.” International journal of pediatric otorhinolaryngology 84 (2016): 132-136.

“Abstract: Objectives: High dose antivirals have been shown to cause hearing loss when applied via the intratympanic route. The aim of this study was to determine if a combination therapy using dexamethasone (DXA) with either Cidofovir (CDV) or Ganciclovir (GCV), in solution or in PLGA-PEG-PLGA (PPP) hydrogel, is innocuous to the inner ear. Methods: Cytomegalovirus (CMV)-free guinea pigs were separated into four principal study groups and treated via intratympanic injection (IT) of CDV/DXA solution, CDV/DXA Hydrogel, GCV/DXA solution and GCV/DXA hydrogel. Hearing thresholds were evaluated with pretreatment ABR and post injection weekly ABRs for a total follow up of 28 days. Temporal bone tissue was harvested and stained with Hematoxylin and Eosin for histologic analysis. Results: ABR analysis revealed that GCV/DXA in solution and in hydrogel led to a mild hearing loss at days 7–21 but returned to baseline by day 28 When administered via PPP hydrogel, CDV/DXA demonstrated mild persistent hearing loss at 32 kHz at 28 days. An inflammatory response was identified in the cochlear specimen of the CDV/DXA/PPP hydrogel group, in concert with mild hearing loss, at days 21 and 28. Conclusion: Results of this study support the safe intratympanic use of higher concentrations of antivirals when combined with DXA, both in solution and when applied via PPP hydrogel. Keywords: Antiviral; Hydrogel; Intratympanic; Dexamethasone; Cidofovir; Ganciclovir”

PolySciTech thermogel investigated as part of system for thermally killing drug-resistant bacteria

PolySciTech division of Akina, Inc ( provides a wide array of research polymers including thermogels. Recently researchers at the University of Toronto have combined PolyVivo AO031 Poly(N-vinylcaprolactam), a biocompatible thermogel, with gold-nanorods to create a thermogelling system that allows for very precise application of heat by a hand-held laser device which kills both gram positive and negative bacteria. This research holds promise for treating infected wounds to kill bacteria without damaging the underlying tissue. Read more:  Mohamed, Mohamed A. Abdou, Vahid Raeesi, Patricia V. Turner, Anu Rebbapragada, Kate Banks, and Warren CW Chan. “A versatile plasmonic thermogel for disinfection of antimicrobial resistant bacteria.” Biomaterials (2016).

“Abstract: The increasing occurrence of antimicrobial resistance among bacteria is a global problem that requires the development of alternative techniques to eradicate these superbugs. Herein, we used a combination of thermosensitive biocompatible polymer and gold nanorods to specifically deliver, preserve and confine heat to the area of interest. Our data demonstrates that this technique can be used to kill both Gram positive and Gram negative antimicrobial resistant bacteria in vitro. Our approach significantly reduces the antimicrobial resistant bacteria load in experimentally infected wounds by 98% without harming the surrounding tissues. More importantly, this polymer-nanocomposite can be prepared easily and applied to the wounds, can generate heat using a hand-held laser device, is safe for the operator, and does not have any adverse effects on the wound tissue and healing process. Keywords: Photothermal; gold nanorods; Thermogel; wound infections; Antibiotic resistant bacteria”

PLGA-PEG-PLGA thermogel investigated for use as a surgical aid in elevating tissues during colon cancer treatment

PolySciTech division of Akina Inc. ( provides a wide-array of biodegradable block copolymers including thermogelling PLGA-PEG-PLGA. Recently, PLGA-PEG-PLGA polymers were used experimentally as a surgical aid in endoscopic submucosal dissection (ESD). This is a procedure which holds great promise for surgical removal of certain types of cancer. For this procedure, the outer mucosa needs to be gently elevated away from the lower submucosa, muscularis, and serosa layers. This allows for a lesion to be cut off the external layer without puncturing the delicate inner layers. Read more about this exciting application here: Cao, Luping, Quanlin Li, Chen Zhang, Haocheng Wu, Liqing Yao, Meidong Xu, Lin Yu, and Jiandong Ding. “Safe and efficient colonic endoscopic submucosal dissection using an injectable hydrogel.” ACS Biomaterials Science & Engineering 2, no. 3 (2016): 393-402.

“Endoscopic submucosal dissection (ESD) has not yet been widely adopted in the treatment of early colonic cancers due to the greater technical difficulty involved, longer procedure time, and the increased risk of perforation. Adequate mucosal elevation by submucosal injection is crucial for en bloc resection and prevention of perforation during colonic ESD. This study is aimed to evaluate the efficacy of an injectable thermoreversible hydrogel as the colonic submucosal agent for the first time. Triblock copolymer poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA–PEG-PLGA) was synthesized, and its concentrated aqueous solution was injected into the colonic submucosa of living minipig and spontaneously transformed into an in situ hydrogel with adequate mucosal elevation at body temperature. Such a mucosal lifting lasted for a longer time than that created by the control group, glycerol fructose. Colonic ESD was then performed with the administration of hydrogels at various polymer concentrations or glycerol fructose. All colonic lesions were successfully resected en bloc after one single injection of the hydrogel, and repeated injections were not needed. No evidence of major hemorrhage, perforation and tissue damage were observed. Considering the injection pressure, duration of mucosal elevation and efficacy of “autodissection”, the hydrogel containing 15 wt % polymer was the optimized system for colonic ESD. Consequently, the thermoreversible hydrogel is an ideal submucosal fluid that provides a durable mucosal lifting and makes colonic ESD accessible to a large extent. In particular, the efficacy of “autodissection” after one single injection of the hydrogel simplifies significantly the procedures while minimizing the complications. Keywords: endoscopic submucosal dissection (ESD); submucosal injection agent; injectable hydrogel; colonic tumor; autodissection”

PolyVivo AK109: Thermogelling PLCL-PEG-PLCL for long-term delivery

PolySciTech division of Akina, Inc. ( provides a wide array of biodegradable block copolymers including thermogelling PLCL-PEG-PLCL AK109. This polymer has a similar LCST property to its PLGA based counter-parts but, unlike PLGA, a much slower degradation time due to slow-degrading PLCL blocks.  Since a 20% w/v aqueous solution of this polymer is liquid it can easily be combined with microparticles or API directly. Then the solution can be injected where body heat solidifies the gel trapping the pharmaceutical so that it elutes out slowly for long term controlled release. You can learn more about in-situ thermogels and their usage in drug delivery in a well-written review article here: He, Chaoliang, Sung Wan Kim, and Doo Sung Lee. “In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery.” Journal of controlled release 127, no. 3 (2008): 189-207.

“Abstract: Stimuli-sensitive block copolymer hydrogels, which are reversible polymer networks formed by physical interactions and exhibit a sol–gel phase-transition in response to external stimuli, have great potential in biomedical and pharmaceutical applications, especially in site-specific controlled drug-delivery systems. The drug may be mixed with a polymer solution in vitro and the drug-loaded hydrogel can form in situ after the in vivo administration, such as injection; therefore, stimuli-sensitive block copolymer hydrogels have many advantages, such as simple drug formulation and administration procedures, no organic solvent, site-specificity, a sustained drug release behavior, less systemic toxicity and ability to deliver both hydrophilic and hydrophobic drugs. Among the stimuli in the biomedical applications, temperature and pH are the most popular physical and chemical stimuli, respectively. The temperature- and/or pH-sensitive block copolymer hydrogels for biomedical applications have been extensively developed in the past decade. This review focuses on recent development of the preparation and application for drug delivery of the block copolymer hydrogels that respond to temperature, pH or both stimuli, including poly(N-substituted acrylamide)-based block copolymers, poloxamers and their derivatives, poly(ethylene glycol)-polyester block copolymers, polyelectrolyte-based block copolymers and the polyelectrolyte-modified thermo-sensitive block copolymers. In addition, the hydrogels based on other stimuli-sensitive block copolymers are discussed. Keywords: Stimuli sensitive; Hydrogel; Block copolymer; Drug delivery; Response”

PolySciTech P(NIPAM-Co-AM) (Polyvivo AO023) used for drop-on-demand (DOD) printing

PolySciTech division of Akina, Inc. ( provides a wide array of thermogelling polymers including gels based of off poly(N-isopropylacrylamind-co-acrylamide) (AO023). One application of this is gel printing. Because it is possible to chill the printing head to dispense the cold liquid thermogel below the polymer LCST and then heat the receiver above the polymer LCST so the thermogel sets, there is the possibility to print gel structures. Eventually, this technology can allow for printing structures using thermogels which incorporate living cells into the printed component which could be used to generate living tissues. Recently, researchers at Purdue University utilized PNIPAM from Akina, along with a developed printing system to create a drop-on-demand system for studying the precise thermogel kinetics, dehydration parameters, and fluid-structure interactions for printing thermogels.  Read more: Han, Bumsoo, Gyu Young Yun, J. William Boley, Samuel Haidong Kim, Jun Young Hwang, George T-C. Chiu, and Kinam Park. “Dropwise gelation-dehydration kinetics during drop-on-demand printing of hydrogel-based materials.” International Journal of Heat and Mass Transfer 97 (2016): 15-25.

“Abstract: The present study aims to characterize and understand the dropwise gelation-dehydration phenomena during drop-on-demand (DOD) printing of hydrogel-based soft materials. Functional soft materials have broader impacts on many medical and engineering applications, but constructing soft materials into three-dimensional (3D) configuration with spatially varying properties is still extremely challenging. In order to establish a mechanistic understanding, a hypothesis was postulated that the porosity of hydrogel printed is determined by dropwise gelation and dehydration phenomena during the printing process. The underlying rationale is that many functional properties of the printed hydrogels are closely associated with the structural characteristics at the sub-droplet and droplet scales, specifically porosity. The porosity of a hydrogel droplet is thought to be determined by intra-droplet fluid–structure interactions during gelation and dehydration. In this study, thus, we characterized the gelation-dehydration and consequent microstructure of thermally responsive poly(N-isopropylacrylamind-co-acrylamide) (PNIPAM) copolymer droplets as a model hydrogel material. The gelation kinetics was studied by differential scanning calorimetry. Both macroscopic and microscopic structures of DOD printed hydrogels were characterized by a 3D profiler and scanning electron microscopy. Furthermore, a theoretical model to explain this complex transport processes was also developed. The results showed that the gelation is a rapid process and its impact is mainly observed at the deposition of droplets. Significant structural shrinkage of the printed hydrogel droplets was induced by dehydration. This shrinkage resulted in spatially varying intra-droplet porosity. A computational model of intra-droplet fluid–structure interactions was developed to explain this spatial variation of intra-droplet porosity. In addition, a new dimensionless parameter is proposed to gauge the significance of evaporation and interstitial water transport in the fluid–structure interactions. Significance of gelation kinetics, dehydration and complex fluid–structure interaction within the droplets was discussed to design a DOD printing process for 3D additive manufacturing of hydrogel-based soft materials. Keywords: Evaporation; Interstitial water transport; Dilatation; Fluid–structure interaction; Consolidation”

Thermogel PLGA-PEG-PLGA investigated for cartilage regeneration as part of arthritis treatment

PolySciTech division of Akina, Inc. ( provides a wide array of biodegradable block copolymers including thermogelling PLGA-PEG-PLGA. This type of polymer transitions from a liquid solution to a solid gel when it is heated from room temperature to body temperature. The benefit of this is it allows for an injected solution to form into a gel once it is introduced into the human body. This is useful for treatment of diseases such as arthritis which may require local delivery to the damaged site. In 2005, an estimated 1.5 million (0.6%) of US adults age ≥ 18 had rheumatoid arthritis which is a disease that attacks cartilage in joints leading to pain and immobility. Recently, researchers published the incorporation of kartogenin in PLGA-PEG-PLGA thermogel and its use in cartilidge repair. Kartogenin induces chondrogenesis by binding the actin-binding protein, filamin A. This disrupts its interaction with the transcription factor core-binding factor β subunit (CBFβ). When dissociated from filamin A, CBFβ translocates to the nucleus and forms a transcriptional complex with RUNX1 thus enabling chondrocyte differentiation. This drug was found to be effectively delivered by the PLGA-PEG-PLGA thermogel locally into the cartilage and this lead to a regerative repair of the cartilage tissue. Read more: Li, Xuezhou, Jianxun Ding, Zheng-Zheng Zhang, Modi Yang, Jia-Kuo Yu, J. C. Wang, Fei Chang, and Xuesi Chen. “Kartogenin-Incorporated Thermogel Supports Stem Cells for Significant Cartilage Regeneration.” ACS applied materials & interfaces (2016).

“Abstract: Recently, cartilage tissue engineering (CTE) attracts increasing attention in cartilage defect repair. In this work, kartogenin (KGN), an emerging chondroinductive non-protein small molecule, was incorporated into a thermogel of poly(L-lactide-co-glycolide)−poly(ethylene glycol)−poly(L-lactide-co-glycolide) (PLGA−PEG−PLGA) to fabricate an appropriate microenvironment of bone marrow mesenchymal stem cells (BMSCs) for effective cartilage regeneration. More integrative and smoother repaired articular surface, more abundant characteristic glycosaminoglycans (GAGs) and collagen II (COL II), and less degeneration of normal cartilage were obtained in the KGN and BMSCs co-loaded thermogel group in vivo. In conclusion, the KGN-loaded PLGA−PEG−PLGA thermogel can be utilized as an alternative support for BMSCs to regenerate the damaged cartilage in vivo.”

Thermogelling PLA-PEG-PLA used in development of post-surgical adhesion prevention

PolySciTech Division of Akina, Inc. ( provides a wide array of biodegradable block copolymers. These include thermogelling PolyVivo AK100 Poly(DL-lactide)-b-Poly(ethylene glycol)-b-Poly(DL-lactide) (P(DL)LA-PEG-P(DL)LA). Recently, researchers at Sichuan University investigated a similar polymer for its use in adhesion prevention. These thermogelling polymers are liquid at room temperature and then transition into a solid gel when the temperature is increased to 37C. This has many uses for applications such as depot drug delivery, vaccine delivery, and prevention of post-surgical adhesion. Post-surgical adhesion is a normal injury response of peritoneal surfaces during surgery which can cause significant morbidity, including bowel obstruction, female infertility, and chronic abdominal and pelvic pain (Diamond MP, Freeman ML. Clinical implications of postsurgical adhesions. Hum Reprod Update 2001; 7:567.) Nationally, about 5.7% of readmissions are due to adhesion with 3.8% requiring operation to fix the problem (Ellis H, Moran BJ, Thompson JN, et al. Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet 1999; 353:1476.) so there is a great need to reduce these adhesions. The researchers found that P(DL)LA-PEG-P(DL)LA presented minimal cytotoxicity or hemolysis, due to its biocompatible nature. They also found that the thermogel polymer led to a significant post-operative adhesion in a rat sidewall defect bowel abrasion model. These results indicate the potential for use of these types of polymers to prevent surgical adhesion. Read more: Shi, K., Wang, Y.L., Qu, Y., Liao, J.F., Chu, B.Y., Zhang, H.P., Luo, F. and Qian, Z.Y., 2016. Synthesis, characterization, and application of reversible PDLLA-PEG-PDLLA copolymer thermogels in vitro and in vivo. Scientific reports, 6.

“Abstract: In this study, a series of injectable thermoreversible and thermogelling PDLLA-PEG-PDLLA copolymers were developed and a systematic evaluation of the thermogelling system both in vitro and in vivo was performed. The aqueous PDLLA-PEG-PDLLA solutions above a critical gel concentration could transform into hydrogel spontaneously within 2 minutes around the body temperature in vitro or in vivo. Modulating the molecular weight, block length and polymer concentration could adjust the sol-gel transition behavior and the mechanical properties of the hydrogels. The gelation was thermally reversible due to the physical interaction of copolymer micelles and no crystallization formed during the gelation. Little cytotoxicity and hemolysis of this polymer was found, and the inflammatory response after injecting the hydrogel to small-animal was acceptable. In vitro and in vivo degradation experiments illustrated that the physical hydrogel could retain its integrity as long as several weeks and eventually be degraded by hydrolysis. A rat model of sidewall defect-bowel abrasion was employed, and a significant reduction of post-operative adhesion has been found in the group of PDLLA-PEG-PDLLA hydrogel-treated, compared with untreated control group and commercial hyaluronic acid (HA) anti-adhesion hydrogel group. As such, this PDLLA-PEG-PDLLA hydrogel might be a promising candidate of injectable biomaterial for medical applications.”