Monthly Archives: April 2015

P(DL)La-glycerol from Polyscitech used for curcumin delivery

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polyesters. This includes 3-arm P(DL)La-glycerol (Mw~15kDa) product number AP092. Recently this material was used for formulating nanoparticles for curcumin delivery which displayed prolonged circulation of curcumin in rat model and good in-vitro anti-cancer activity. Read more: Yoon, In-Soo, Ju-Hwan Park, Hyo Jin Kang, Ji Hyeong Choe, Min Su Goh, Dae-Duk Kim, and Hyun-Jong Cho. “Poly (d, l-lactic acid)-glycerol-based nanoparticles for curcumin delivery.” International Journal of Pharmaceutics (2015).  http://www.sciencedirect.com/science/article/pii/S0378517315003543

“Abstract: Poly(d,l-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intravenous delivery of curcumin (CUR). NPs with a mean diameter of approximately 200 nm, a narrow size distribution, and capable of efficient drug encapsulation were prepared using an emulsification-solvent evaporation method. The stability of NPs was verified in water, phosphate buffered saline (PBS), and serum after 24-h incubation. A sustained drug release pattern was observed, and the amount of CUR released in acidic media (pH 5.5) was higher than in media at physiological pH (pH 7.4). Blank NPs (without drug loading) did not exhibit severe cytotoxicity in MDA-MB-231 human breast adenocarcinoma cells. The in vitro anti-tumor efficacy of CUR-loaded NPs in MDA-MB-231 cells was comparable to that of a solution of CUR. Pharmacokinetic studies in rats showed that the in vivo clearance (CL) of CUR in the NP-treated group was lower than the group treated with CUR solution. Therefore, encapsulation of CUR in PDLLA-G NPs was shown to enable prolonged circulation of the drug in the blood stream and guarantee improved anticancer activity after intravenous injection. These biocompatible NPs could be an efficient nano-sized injectable formulation for CUR delivery.”

Yoon, 2015 PLA-glycerol curcumin delivery

PEG-PLA used to create hydrogel-microparticle polymersome

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable block copolymers including PEG-PLA. Recently this kind of polymer was utilized to generate cell-like hydrogel/microparticle structures. Read more: Martino, Chiara, Tae Yong Lee, and Shin-Hyun Kim. “Microfluidic generation of PEG-b-PLA polymersomes containing alginate-based core hydrogel.” Biomicrofluidics 9, no. 2 (2015): 024101. http://scitation.aip.org/content/aip/journal/bmf/9/2/10.1063/1.4914112

“Abstract: Herein, we demonstrate a novel method for the generation of monodisperse cell-like structures containing a biocompatible hydrogel matrix surrounded by a membrane responsive to chemical cues. Specifically, we employ droplet-based microfluidics to generate PEG-PLA polymersomes encapsulating alginate in liquid form. We investigate alginate core gelation by creating an osmotic pressure gradient across the polymeric membrane that, through expansion, allows the passage of calcium ions. The effects of calcium concentration on the core gelation are explored.”

mPEG-PLA from PolySciTech used for resveratrol delivery system

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable block copolymers including mPEG-PLA. Recently a publichation by Curtin University has reported on the use of mPEG-PLA as a precursor for a resveratrol conjugate system. Read more: Siddalingappa B, Benson HAE, Brown DH, Batty KT, Chen Y (2015) Stabilization of Resveratrol in Blood Circulation by Conjugation to mPEG and mPEG-PLA Polymers: Investigation of Conjugate Linker and Polymer Composition on Stability, Metabolism, Antioxidant Activity and Pharmacokinetic Profile. PLoS ONE 10(3): e0118824. doi:10.1371/journal.pone.0118824 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118824

“Abstract: Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing different chemical linkers and polymer compositions was investigated for enhanced pharmacokinetic profile of resveratrol. Ester conjugates such as α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol (MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol (MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were synthesized by alkali-mediated etherification. All polymer conjugates were fully characterized in vitro and the pharmacokinetic profile of selected conjugates was characterized in rats. Buffer and plasma stability of conjugates was dependent on polymer hydrophobicity, aggregation behavior and PEG corona, with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in vitro. Polymer conjugates irrespective of linker chemistry protected resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa), Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles with significantly higher plasma area under curve (AUC), slower clearance and smaller volume of distribution, compared to resveratrol.”

PolySciTech PLGA used for subcutaneous nanoparticle delivery of heparin

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA. Recently PLGA from Polyscitech was utilized for nanoparticle delivery of heparin in order to evaluate the effect of different types (e.g. different lactide ratios) of PLGA on drug release. Read more: Jogala, S., S. S. Rachamalla, and J. Aukunuru. “Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin.” Journal of Advanced Pharmaceutical Technology & Research 6, no. 2 (2015): 58. http://japtr.org/article.asp?issn=2231-4040;year=2015;volume=6;issue=2;spage=58;epage=64;aulast=Jogala

“Abstract: The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c.) nanoparticles of low molecular weight heparin (LMWH). The nanoparticles were prepared by water-in-oil in-water (w/o/w) emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15), and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1%) aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity) using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16-38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH. Keywords: Anti-factor Xa activity, low molecular weight heparin, nanoparticles, polylactide co-glycolide, subcutaneous, sustained release”

PolySciTech PLGA-PEG-COOH (AI34) used for targeted salinomycin cancer delivery

PolySciTech (www.polyscitech.com) provides a wide variety of reactive precursors. Recently polyvivo AI34 (PLGA-PEG-COOH) was utilized along with EDC/NHS chemistry to conjugate CD133 aptamer onto the exterior of the nanoparticle and used for delivery to cancer cells. Read more: Ni, Miaozhong, Min Xiong, Xinchao Zhang, Guoping Cai, Huaiwen Chen, Qingmin Zeng, and Zuochong Yu. “Poly (lactic-co-glycolic acid) nanoparticles conjugated with cD133 aptamers for targeted salinomycin delivery to cD133+ osteosarcoma cancer stem cells.” International Journal of Nanomedicine 10 (2015): 2537. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386781/

“Abstract: Background: Cancer stem cells (CSCs) possess the characteristics associated with normal stem cells and are responsible for cancer initiation, recurrence, and metastasis. CD133 is regarded as a CSCs marker of osteosarcoma, which is the most common primary bone malignancy in childhood and adolescence. Salinomycin, a polyether ionophore antibiotic, has been shown to kill various CSCs, including osteosarcoma CSCs. However, salinomycin displayed poor aqueous solubility that hinders its clinical application. The objective of this study was to develop salinomycin-loaded nanoparticles to eliminate CD133+ osteosarcoma CSCs. Methods: The salinomycin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles (SAL-NP) conjugated with CD133 aptamers (Ap-SAL-NP) were developed by an emulsion/solvent evaporation method, and the targeting and cytotoxicity of Ap-SAL-NP to CD133+ osteosarcoma CSCs were evaluated. Results: The nanoparticles are of desired particle size (~150 nm), drug encapsulation efficiency (~50%), and drug release profile. After 48 hours treatment of the Saos-2 CD133+ osteosarcoma cells with drugs formulated in Ap-SAL-NP, SAL-NP, and salinomycin, the concentrations needed to kill 50% of the incubated cells were found to be 2.18, 10.72, and 5.07 μg/mL, respectively, suggesting that Ap-SAL-NP could be 4.92 or 2.33 fold more effective than SAL-NP or salinomycin, respectively. In contrast, Ap-SAL-NP was as effective as SAL-NP, and less effective than salinomycin in Saos-2 CD133− cells, suggesting that Ap-SAL-NP possess specific cytotoxicity toward Saos-2 CD133+ cells. Ap-SAL-NP showed the best therapeutic effect in Saos-2 osteosarcoma xenograft mice, compared with SAL-NP or salinomycin. Significantly, Ap-SAL-NP could selectively kill CD133+ osteosarcoma CSCs both in vitro and in vivo, as reflected by the tumorsphere formation and proportion of Saos-2 CD133+ cells. Conclusion: Our results suggest that CD133 is a potential target for drug delivery to osteosarcoma CSCs and that it is possible to significantly inhibit the osteosarcoma growth by killing CD133+ osteosarcoma CSCs. We demonstrated that Ap-SAL-NP have the potential to target and kill CD133+ osteosarcoma CSCs. Keywords: targeted therapy, ligand-conjugated nanomedicines, cancer initiating cells”

PolySciTech products used for aerosol delivery

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including Mal-PEG-PLGA. Recently this polymer was utilized to generate STL labelled nanoparticles for aerosol delivery across the blood-brain-barrier. Read more: Justin E. Piazza, Chao Zhu, Ravi Selvaganapathy, Todd Hoare, Saransh B. Jain, Farhat Hossain and Ram K. Mishra “The Use of a Novel Intranasal Spray Device for the Administration of Nanoparticles for the Treatment of Rodents” ASME. J. Med. Devices. 2015;():. doi:10.1115/1.4029907 http://medicaldevices.asmedigitalcollection.asme.org/article.aspx?articleid=2174069

“Abstract: Experimental intranasal delivery of nanoparticle drug carriers is typically performed using a pipette with or without anaesthesia, a technique that may be a poor simulation of practical intranasal administration of drug-loaded nanoparticles in humans. Existing intranasal spray devices suffer from drawbacks in terms of variability in dose-control and spray duration as well as the application of non-uniform pressure fields when a nanoparticle-formulated drug is aerosolized. Furthermore, existing spray devices require large volumes that may not be available or may be prohibitively expensive to prepare. In response, we have developed a novel pneumatically-driven intranasal spray device for the administration of nanoparticles that is capable of administering extremely small quantities (50-100 µL) of nanoparticle suspension in a fine spray that disperses the nanoparticles uniformly on to the tissue. This device was validated using haloperidol-loaded Solanum tuberosum lectin (STL)-functionalized, poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PEG-PLGA) nanoparticles targeted for delivery to the brain for schizophrenia treatment. A pneumatic pressure of 100 kPa was found to be optimal to produce a spray that effectively aerosolizes nanoparticle suspensions and delivers them evenly to the olfactory epithelium. Intranasal administration of STL-functionalized nanoparticles using the intranasal spray device increased brain tissue haloperidol concentrations by a factor of 1.2-1.5x compared to STL-functionalized nanoparticles administered intranasally with a pipette. Such improved delivery enables the use of lower drug doses and thus offers both fewer side-effects and lower costs without compromising therapeutic efficacy.”

Akina, Inc. Non-Discrimination Policy

Akina, Inc., including the PolySciTech Division (www.polyscitech.com), are based in West Lafayette, Indiana. Non-discrimination of customers has always been a policy at Akina, Inc. Due to recent legal ambiguity regarding this subject, the Akina Non-Discrimination policy has been formally added to our standard terms and conditions (https://akinainc.com/polyscitech/Terms-and-Conditions.php). This policy is listed as term #18 as follows: “Akina, Inc. provides products and services to customers regardless of race, religion, color, sex, age, national origin or ancestry, marital status, parental status, sexual orientation, gender identity, disability, or veteran status.”