Wednesday, November 15, 2017

PLA from PolySciTech used in development of nanoparticle-based triple-negative breast cancer therapy

Most forms of breast cancer respond well to conventional therapies, such as doxorubicin. There is, however, a specific type of breast cancer that is referred to as ‘triple-negative’ (named this because it does not have receptors for estrogen, progesterone, or HER2) breast cancer. It is highly resistant to conventional chemotherapy and very invasive. Recently, researchers at University of Cincinnati utilized polylactide (AP128) from PolySciTech (www.polyscitech.com) to develop chemotherapy particles which released gefitinib followed by sequential release of doxorubicin. These particles were found to be significantly more effective at treating triple-negative breast cancer than . This research holds promise for developing more effective chemotherapy strategies to treat breast cancer. Read more: Zhou, Zilan, Mina Jafari, Vishnu Sriram, Jinsoo Kim, Joo-Youp Lee, Sasha J. Ruiz-Torres, and Susan E. Waltz. "Delayed Sequential Co-Delivery of Gefitinib and Doxorubicin for Targeted Combination Chemotherapy." Molecular Pharmaceutics (2017). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00669

“There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal growth factor receptor (EGFR) signaling applicable for the treatment of triple negative breast cancers. To realize this nanoparticle design, Gi complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(l-lactide)-block-polyethylene glycol (PLA-b-PEG) and with an encapsulation efficiency of ∼90%. The nanoparticle system exhibited a desired sequential release of Gi followed by Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated approximate 4-fold and 3-fold increases in anticancer efficacy compared to a control group of Dox–PLA-PEG conjugate against MDA-MB-468 and A549 cell lines in terms of half maximal inhibitory concentration (IC50), respectively. High tumor accumulation of the nanoparticle system was also substantiated for potential in vivo applicability by noninvasive fluorescent imaging. Keywords: combination therapy; controlled delivery; doxorubicin; EGFR inhibitor; nanoparticles; sequential delivery”

PLGA and PLGA-rhodamine from PolySciTech used in study on chemotherapeutic delivery by nanoparticles

For conventional, loose-drug, chemotherapy, less than 1% of the injected medicine actually makes it to the tumor site. The clinical method for solving this problem has been to inject massive doses of chemotherapeutic agents to the patient, in the hopes that at least some of the medicine makes it to the tumor. This is not a good solution to this problem and leads to substantial morbidity from the side-effects of chemotherapy (hair loss, immune-system damage, etc.). Nanoparticle-based technologies have been developed in the hopes of creating a system in which the drug is encapsulated in a small particle that flows through the blood until it is entrapped by the tumor. Although coating the particle with PEG improves its circulation time, it can also hinder uptake by the tumor. Recently, researchers from Purdue University and Eli Lilly and Company used PLGA (PolyVivo AP020) and Rhodamine-labelled PLGA (Polyvivo AV011) from PolySciTech (www.polyscitech.com) to develop chitosan-coated nanoparticles with preferential tumor attraction over PEGylated nanoparticles. They found, however, that although the particles were preferentially absorbed by the polymer, the drug itself (in the study, ICG tracer-dye was used) leached out too quickly to be of any use. This highlights how critical the drug-entrapment strategy is to the overall design of a nanoparticle formulation. This research holds promise to provide for improved chemotherapeutic strategies with reduced side-effects. Read more: Park, Jinho, Yihua Pei, Hyesun Hyun, Mark A. Castanares, David S. Collins, and Yoon Yeo. "Small molecule delivery to solid tumors with chitosan-coated PLGA particles: A lesson learned from comparative imaging." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917309367

“Abstract: For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs. Keywords: pH-responsive Drug delivery PLGA nanoparticles Small molecules In vivo imaging Encapsulation stability”

Thursday, November 9, 2017

PLGA-PEG-NHS from PolySciTech used as part of nanoparticle-protected-islets based treatment of diabetes


Type 1 Diabetes is a chronic disease brought on by loss of function of pancreatic islets, groups of cells that produce insulin to regulate the blood sugar content. Recently, transplantation of pancreatic islets has been considered as a long-term treatment for type 1 diabetes that does not require the patient to take daily injections of insulin. Immune-system rejection of the transplant, however, creates difficult for this treatment method as the body attacks the newly transplanted cells. One means of preventing this is to encapsulate the cells in a material which is non-immunogenic so as to protect them from macrophages. Recently, researchers at Yeungnam University, Seoul National University, and Keimyung University (Korea) utilized PolyVivo AI111 (PLGA-PEG-NHS) from PolySciTech (www.polyscitech.com) to create pegylated nanoparticles which attach to the islet cells and prevent them from being attacked by the immune system. This research holds promise to provide for a long-term treatment of diabetes which does not require the patient to continuously inject insulin. Read more: Pham, Tung Thanh, Tiep Tien Nguyen, Shiva Pathak, Shobha Regmi, Hanh Thuy Nguyen, Tuan Hiep Tran, Chul Soon Yong et al. "Tissue adhesive FK506–loaded polymeric nanoparticles for multi–layered nano–shielding of pancreatic islets to enhance xenograft survival in a diabetic mouse model." Biomaterials (2017). http://www.sciencedirect.com/science/article/pii/S014296121730707X

“Abstract: This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4–dihydroxyl–l–phenylalanine (DOPA) conjugated poly(lactide–co–glycolide)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (DOPA–NPs) carrying immunosuppressant FK506 (FK506/DOPA–NPs). The functionalized DOPA–NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co–culture condition with xenogenic lymphocytes for 7 days. Interestingly, the mean survival time of islets coated with FK506/DOPA–NPs was significantly higher as compared with that of islets coated with DOPA–NPs (without FK506) and control. This study demonstrated that the combination of surface camouflage and localized low dose of immunosuppressant could be an effective approach in prolonging the survival of transplanted islets. This newly developed platform might be useful for immobilizing various types of small molecules on therapeutic cells and biomaterial surface to improve the therapeutic efficacy in cell therapy and regenerative medicine. Keywords: Surface modification; FK506; Islets transplantation; Local delivery; Diabetes mellitus”

Wednesday, November 1, 2017

PLGA-PEG-PLGA from PolySciTech used for localized propranolol delivery system


Hemangioma (red or purple colored birthmarks) is a benign childhood tumor generated by excessive growth of blood vessels. Although external hemangioma’s typically only affect aesthetics, the growth of internal hemangiomas, especially near liver, brain, or other critical organs, can cause severe pain and morbidity.  Treatment options include corticosteroids and beta-blockers, however applying such treatments to infants and children throughout the whole body in a systemic fashion can create problems with controlling the dose and side-effects. Recently, researchers at Henan Provincial People’s Hospital and the Second Military Medical University (China) used PLGA-PEG-PLGA (PolyVivo AK016) from PolySciTech (www.polyscitech.com) to generate microparticles as part of a local propranolol delivery system. These particles were found to be effective at delivering propranolol (a beta blocker) locally without requiring a large systemic dose. This research holds promise for treating a variety of conditions where excessive angiogenesis is a problem. Read more: Guo, Xiaonan, Xiaoshuang Zhu, Dakan Liu, Yubin Gong, Jing Sun, and Changxian Dong. "Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth." International Journal of Nanomedicine 12 (2017): 6923. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609781/


“Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM) as a novel topical release system to realize sustained release of propranolol. Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs) in microspheres made of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymers (PLGA-PEG-PLGA). The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs). Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma. Results: The microspheres were of desired particle size (~77.8 μm) and drug encapsulation efficiency (~23.9%) and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF]) in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0 .001="" a="" and="" approach="" conclusion:="" controlled="" deliver="" density="" efficiently="" findings="" group="" groups="" hemangioma.="" hemangioma="" infantile="" inhibition="" is="" keywords:="" leading="" liposomes="" locally="" lower="" mean="" microsphere="" microvessel="" mm2="" o:p="" of="" other="" our="" p="" pl:="" pl="25" plim-treated="" plim="" promising="" propranolol:="" propranolol="" release="" saline:="" saline="40" show="" significant="" significantly="" site="" than="" that="" the="" to="" very="" vessels="" vs="" was="">

Tuesday, October 31, 2017

PLGA-Glucose from PolySciTech used in cancer glucose-targeting nanoparticle development for cancer therapy

Cancer cells are typically be considered to act ‘hungry,’ as they consume glucose and oxygen at much faster rates than normal cells. For this, they have over-expressed glucose uptake moieties to absorb more of this energy filled sugar. This provides one method of targeting cancer which is to focus on their over-uptake of glucose as a targeting strategy. Recently, researchers at Seoul National University and Kangwon National University (Korea) utilized PLGA and PLGA-glucose from PolySciTech (www.polyscitech.com) (PolyVivo AP027 (PLGA-glucose) and AP041 (PLGA)) to create nanoparticles which target to the glucose uptake transporters of cancer cells. This research holds promise for improved cancer treatments by targeted delivery. Read more: Park, Ju-Hwan, Hyun-Jong Cho, and Dae-Duk Kim. "Poly ((D, L) lactic-glycolic) acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting." International Journal of Nanomedicine 12 (2017): 7453. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644567/


“Poly((D,L)lactic-glycolic)acid–star glucose (PLGA-Glc) polymer-based nanoparticles (NPs) were fabricated for tumor-targeted delivery of docetaxel (DCT). NPs with an approximate mean diameter of 241 nm, narrow size distribution, negative zeta potential, and spherical shape were prepared. A sustained drug release pattern from the developed NPs was observed for 13 days. Moreover, drug release from PLGA-Glc NPs at acidic pH (endocytic compartments and tumor regions) was significantly improved compared with that observed at physiological pH (normal tissues and organs). DCT-loaded PLGA-Glc NPs (DCT/PLGA-Glc NPs) exhibited an enhanced antiproliferation efficiency rather than DCT-loaded PLGA NPs (DCT/PLGA NPs) in Hep-2 cells, which can be regarded as glucose transporters (GLUTs)-positive cells, at ≥50 ng/mL DCT concentration range. Under glucose-deprived (hypoglycemic) conditions, the cellular uptake efficiency of the PLGA-Glc NPs was higher in Hep-2 cells compared to that observed in PLGA NPs. Cy5.5-loaded NPs were prepared and injected into a Hep-2 tumor-xenografted mouse model for in vivo near-infrared fluorescence imaging. The PLGA-Glc NPs group exhibited higher fluorescence intensity in the tumor region than the PLGA NPs group. These results imply that the PLGA-Glc NPs have active tumor targeting abilities based on interactions with GLUTs and the hypoglycemic conditions in the tumor region. Therefore, the developed PLGA-Glc NPs may represent a promising tumor-targeted delivery system for anticancer drugs. Keywords: PLGA-Glc, nanoparticles, glucose transporter, hypoxia, tumor targeting”

Tuesday, October 24, 2017

PLGA and PLCL from PolySciTech used in development of biodegradable foam for advanced wound treatment


One means to encourage wound healing, in either chronic or traumatic wounds, is to reduce the pressure across the wound surface to encourage local blood-flow, stimulate healing, and draw out excess fluids. This requires placing a sterile foam over the top of the wound and connecting the foam to a vacuum pump with an air-tight cover to apply vacuum to the wound. Conventionally, this is done with a non-degradable polyurethane-type foam. During this treatment, tissue often grows into the foam, which creates significant problems upon changing the dressing as fresh-grown tissue can be damaged. Recently, researchers at Wake Forest University utilized multiple PLGA, PLCL, and PCL products (PolyVivo AP037, AP081, AP036, AP073, AP013, and AP015) from PolySciTech (www.polyscitech.com) to develop a degradable, compressible foam for wound therapy. This research holds promise for development of improved wound-therapy methods using foams that simply resorb into the body rather than have problems with in-growth. Read more: Warner, Harleigh J., and William D. Wagner. "Fabrication of biodegradable foams for deep tissue negative pressure treatments." Journal of Biomedical Materials Research Part B: Applied Biomaterials. http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.34007/full

“ABSTRACT: Devices for negative pressure wound therapy (NPWT) rely on compressible foams operating at the tissue-device interface. Clinically used foams are nonabsorbable and if used on deep wounds or left in place for an extended period of time, excessive cell ingrowth and formation of granulation tissue into the foam may require a surgical procedure to remove the foam. Foams with fast degradation and with low immunogenicity and fibrotic response are required. Foams composed of combinations of poly(lactide-co-glycolide) (PLGA), poly(lactide-co-caprolactone) (PLCL), and polycaprolactone (PCL) were created by combined salt leaching and solvent displacement protocols. In vitro and in vivo degradation studies and mechanical properties of foams were evaluated and compared to clinically used poly(vinyl alcohol) (PVA) foam and PCL foams. Foams composed of PLGA (50:50 lactide:glycolide) of low molecular weight blended with PCL maintained mechanical properties and degraded significantly after 21 days of subcutaneous implantation in rats. The most ideal formulations for use in NPWT were identified as copolymeric PLGA (Mn 3000 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at either a 75:25 or 50:50 ratio, and copolymeric PLGA (Mn 7500 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at a 50:50 ratio. KeyWords: polyester, polycaprolactone, poly(lactic-co-glycolic acid), foams, negative pressure wound therapy”

Monday, October 23, 2017

PLGA-PEG-PLGA thermogel from PolySciTech used in development of delivery system for ovarian cancer treatment


Ovarian cancer is particularly difficult to treat in a clinical setting as it has relatively few symptoms before progressing to an advanced stage. Chemotherapeutic agents tend to work well initially, but the cancer can become resistant quickly. One means to counter this is to apply drugs through the intraperitoneal route, a direct injection into the abdominal cavity. This allows for maximum exposure of the cancer to the chemotherapeutics. This, however, requires a thermogel delivery system which can trap the drug and allow for slow, controlled release of the compounds after the injection. Recently, researchers at University of Wisconsin-Madison and Mokpo National University (Korea), purchased PLGA-PEG-PLGA (PolyVivo AK012) from PolySciTech (www.polyscitech.com). They utilized this polymer to generate a thermogel and deliver chemotherapeutic agents epothilone B (EpoB), rapamycin, and tanespimycin. They found good pre-clinical results in reducing the growth of ovarian cancer cells by delivering these agents. This research holds promise for improved ovarian cancer treatment options. Read more: Shin, Dae Hwan, and Glen S. Kwon. "Pre-clinical evaluation of a themosensitive gel containing epothilone B and mTOR/Hsp90 targeted agents in an ovarian tumor model." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917309069


“Abstract: Despite clinical remission of epithelial ovarian cancer (EOC) after surgical resection and first-line chemotherapy, about 60% of patients will re-develop peritoneal metastasis and about 50% will relapse with chemoresistant disease. Clinical studies suggest that intra-peritoneal (i.p.) chemotherapy effectively treats residual EOC after cyto-reduction by gaining direct access into the peritoneal cavity, enabling elevated drug levels versus intravenous (i.v.) injection. However, chemoresistant disease is still problematic. To overcome resistance against microtubule stabilizing agents such as taxanes, epothilone B (EpoB) has merit, especially in combination with molecular targeted agents that inhibit heat shock protein 90 (Hsp90) and/or mammalian target of rapamycin (mTOR). In this paper, we report on the successful loading and solubilization of EpoB in a poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(d,l-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) thermosensitive gel (g-E). Further, we report on successful co-loading of 17-AAG (Hsp90) and rapamycin (mTOR) (g-EAR). After i.p. injection in mice, g-EAR showed gelation in the peritoneum and sustained, local-regional release of EpoB, 17-AAG, and rapamycin. In a luciferase-expressing ES-2 (ES-2-luc) ovarian cancer xenograft model, single i.p. injections of g-E and g-EAR delayed bioluminescence from metastasizing ES-2-luc cells for 2 and 3 weeks, respectively, despite fast drug release for g-EAR in vivo versus in vitro. In summary, a PLGA-b-PEG-b-PLGA sol-gel has loading and release capacities for EpoB and its combinations with 17-AAG and rapamycin, enabling a platform for i.p. delivery, sustained multi-drug exposure, and potent antitumor efficacy in an ES-2-luc, ovarian cancer i.p. xenograft model. Keywords: Drug combination; Epothilone B; Intraperitoneal injection; Ovarian cancer; Peritoneal carcinomatosis; Thermogel”