Wednesday, August 3, 2022

PLCL from PolySciTech: Akina used in development of nanoparticles for delivery of SN-38 as colorectal cancer therapy

 

Colon cancer is statistically the third most fatal malignancy worldwide. Almost 50% of patients develop metastatic colon cancer which is a highly fatal condition. Recently, researchers at University of Prishtina (Kosovo), TardigradeNano LLC (California), and San Diego State University used PLCL (cat# AP103) from PolySciTech division of Akina (www.polyscitech.com) along with pluronic to formulate a series of nanoparticles containing SN-38. They tracked the effects of these particles on the gene regulation of colorectal cancer cells with nanoparticles that have a wide pluronic corona or a collapsed one. This study holds promise to improve nanoparticle therapies of cancer in the future. Read more: Koliqi, Rozafa, Arlinda Daka Grapci, Pranvera Breznica Selmani, and Vuk Uskoković. "Gene Expression Effects of the Delivery of SN-38 via Poly (DL-lactide-co-caprolactone) Nanoparticles Comprising Dense and Collapsed Poloxamer Coronae." Journal of Pharmaceutical Innovation (2022): 1-9. https://link.springer.com/article/10.1007/s12247-022-09672-8

“Purpose: SN-38 is an antineoplastic drug with a three orders of magnitude higher activity than its prodrug, irinotecan, a common chemotherapeutic of choice in the treatment of colorectal cancer. A considerable number of genes are known to alter their expression under the influence of free SN-38, but no studies have looked at the gene expression effects of SN-38 delivered via poly(D-L-lactide-co-caprolactone) (PLCL) nanoparticles yet. Method: We evaluated changes to expression levels of genes encoding for ubiquitin D (UBD), fibroblast growth factor 3 (FGF3), histone (HIST), and regulator of cell cycle (RGCC) in SW-480 colon cancer cells in response to free SN-38 and two types of poloxamer-coated PLCL (PEO-PPO-PEO/PLCL) nanoparticles as carriers for SN-38, containing different conformations of the hydrophilic stealth corona: dense or collapsed. Results: Both the free drug and the two drug-loaded nanoformulations upregulated UBD and RGCC and downregulated FGF3 and HIST, which was consistent with the pharmacological activity of SN-38. Still, there was a clear difference in gene expression levels in SW-480 cells depending on whether they were challenged with free SN-38 or with nanoparticles loaded with SN-38. Most critically, the delivery of SN-38 with the nanoparticles prolonged its mode of action and, in the case of genes such as UBD, FGF3, and HIST, provided for a more intense effect on gene expression alteration than that achieved by the drug alone. Conclusions: Nanoparticles comprising the collapsed PEO-PPO-PEO corona produced a more intense effect on gene expression alteration than the nanoparticles with the dense PEO-PPO-PEO corona.”

Wednesday, July 27, 2022

PLA from PolySciTech:Akina used in development of inulin-PLA copolymer for cancer therapy

 


While poly(ethylene glycol) is commonly applied to create long-circulating nanoparticles, certain patients develop PEG allergic reactions requiring alternative options. Recently, researchers at University of Salerno (Italy) PLA (cat# AP005, AP231) and mPEG-PLA (cat# AK009) from PolySciTech division of Akina (www.polyscitech.com) to develop long-circulating nanoparticles for drug delivery applications. This research holds promise to improve development of nanotherapies in the future. Read more: Sardo, Carla, Teresa Mencherini, Carmela Tommasino, Tiziana Esposito, Paola Russo, Pasquale Del Gaudio, and Rita Patrizia Aquino. "Inulin-g-poly-D, L-lactide, a sustainable amphiphilic copolymer for nano-therapeutics." Drug Delivery and Translational Research (2022): 1-17. https://link.springer.com/article/10.1007/s13346-022-01135-4

“Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy while maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, is a winning choice to ensure a long circulation and colloidal stability, while in some cases, patients could develop PEG-directed immunoglobulins after the first administration. This lead to a phenomenon called accelerated blood clearance (ABC effect), and it is correlated with clinical failure because of the premature removal of the nanosystem from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility, and its GRAS status, the natural polysaccharide inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-g-poly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physicochemical point of view (solubility, 1D and 2D NMR, FT-IR, UV–Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well-known and well-characterized PEGylated counterpart, polyethylene glycol-b-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues.”

PCL from PolySciTech:Akina used in development of long-acting monoclonal antibody delivery system.

 

Monoclonal antibodies, or mAbs, are a type of protein made in a laboratory to fight a particular infection (SARS-CoV-2 or certain cancers). These are difficult to deliver due to their tendency to denature. Recently, researchers at University of Cincinnati used PCL (Cat# AP011) from PolySciTech division of Akina (www.polyscitech.com) to develop long-acting anti-body releasing porous implant. This research holds promise to improve the use of this class of pharmaceuticals. Read More: Waterkotte, Thomas, Xingyu He, Apipa Wanasathop, S. Kevin Li, and Yoonjee C. Park. "Long-term Antibody Release Polycaprolactone (PCL) Capsule and the Release Kinetics In Natural and Accelerated Degradation." bioRxiv (2022). https://www.biorxiv.org/content/10.1101/2022.06.06.493286.abstract

“Although therapy using monoclonal antibodies (mAbs) has been steadily successful over the last 20 years, the means of delivery of mAbs has not been optimized, especially for long-term delivery. Frequent injections or infusions have been current standard of care. In this study, we have developed a long-term antibody biodegradable implant using a porous polycaprolactone (PCL) capsule. It released Bevacizumab (Bev) slowly for 8 months to date. The Bev release kinetics fit a drug release model with experimental data of the diffusion coefficient and partition coefficient through the polymer capsule. Since screening drug release profiles for the long-term (> 6 months) is time consuming, an accelerated degradation method was used after validating characteristics of the PCL capsule in natural and accelerated degradation conditions. The correlation of time period between the natural and the accelerated degradation was determined. Overall, the study suggests mAbs can be released from a porous PCL capsule without an effect of the polymer degradation over the long period (~ 6 months) and the long-term release kinetics can be determined by the accelerated degradation within 14 days.”

PLGA-Rhodamine from PolySciTech used in development of arthritis treatment

 


Osteoarthritis is the most common form of arthritis, affecting millions of people worldwide. It occurs when the protective cartilage that cushions the ends of the bones wears down over time. Recently, researchers at Chungnam National University, Seoul National University and Chungbuk National University (Korea) utilized PLGA-Rhodamine (Cat# AV011) from PolySciTech division of Akina (www.polyscitech.com) to make traceable nanoparticles for tracking the particle location as part of development of osteoarthritis treatment. This research holds promise to improve treatment against arthritis. Read more: Park, Hyewon, Ha-Reum Lee, Hyo Jung Shin, Ji Ah Park, Yongbum Joo, Sun Moon Kim, Jaewon Beom, Seong Wook Kang, Dong Woon Kim, and Jinhyun Kim. "p16INK4a-siRNA nanoparticles attenuate cartilage degeneration in osteoarthritis by inhibiting inflammation in fibroblast-like synoviocytes." Biomaterials Science (2022). https://pubs.rsc.org/en/content/articlehtml/2022/bm/d1bm01941d

“In osteoarthritis (OA), chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favoring disease progression. Although senescence biomarker p16INK4a expression is known to induce aging by halting the cell cycle, therapeutic applications for p16INK4a targeting are limited. Here, we aimed to reduce cartilage damage and alleviate pain using p16INK4a nanoparticles in OA. The p16INK4a expression of human OA chondrocytes and synoviocytes from patients with knee OA was measured and the levels of p16INK4a, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP) 13 were examined. p16INK4a siRNA was encapsulated into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and characterized. The partial medial meniscectomy (pMMx) model was performed for the OA model which was investigated by molecular analysis and behavioral tests. The expression of p16INK4a was increased in the synovium and articular cartilage from OA patients. p16INK4a siRNA-loaded PLGA nanoparticles (p16 si_NP) reduced the levels of TNF-α, IL-1β, and IL-6 especially in fibroblast-like synoviocytes (FLSs), and MMP13 in chondrocytes. Rhodamine-tagged NPs injected into the mouse knee joints were found mainly in the synovium. p16 si_NP injection in the pMMx model alleviated pain-associated behavior, and reduced cartilage damage and p16INK4a in the synovium, and MMP13, collagen X, and NITEGE in cartilage. The preferential reduction of p16INK4a in FLSs by the application of RNAi nanomedicine could contribute to the recovery of osteoarthritic cartilage and relieve pain, suggesting that p16INK4a may be a viable future therapeutic candidate.”

PLA from PolySciTech used in development of treatment of gastroschisis

 

Reported gastroschisis has increased over the past 25 years from 0.1 cases per 10,000 to 1 case per 10,000 live births in developed countries, and from 3 to 5 cases per 10,000 births in developing countries. Recently, researchers from Universitas Airlangga (Indonesia) utilized PLLA (cat# AP006) from PolySciTech division of Akina (www.polyscitech.com) to develop spring-loaded drug delivery systems for treatment of gastroschisis. This research holds promise to improve treatments against this birth defect. Read more: Widiyanti, Prihartini, Fahreza Rachmat Yoviansyah, and Djony Izak Rudyarjo. "Poly L-Lactic Acid (Plla)-Collagen Coating Chitosan as a Spring-Loaded Silo Candidate for Gastroschisis." Journal of International Dental and Medical Research 15, no. 2 (2022): 950-955. http://www.jidmr.com/journal/wp-content/uploads/2022/06/77-MD22_1740_Prihartini_Widiyanti_Indonesia.pdf

“Abstract: Gastroschisis is one of the birth defects with organ conditions that come out of the abdominal cavity. The handling of gastroschisis is conducted by the staged closure method or wrapping the organ that comes out to be inserted slowly using gravity and a spring-loaded silo. To overcome this problem, a research study was conducted to find candidates for spring loaded silos with the combination of 5% PLLA, collagen with various concentrations (1, 0.75, 0.5, and 0.25)%, and 1% chitosan which was expected to reduce the risk of side effects in infants with gastroschisis such as infections and microbes. It can also improve the mechanical properties of the spring-loaded silo membrane. Based on the FTIR test, it showed the functional groups of PLLA (Ester), Collagen (Amide), and Chitosan (Amine). The SEM results showed that the overall pore value was 4.42-6.67 µm, thus it can meet the goretex pore size with a pore size range of 0-25 µm. The results of the tensile strength test, the UTS value on the abdominal wall was 2 - 9.2 MPa, thus the K2 sample with a value of 8.56 MPa has met and the value of the Elasticity Modulus of the linear alba layer on the abdominal wall was 23 - 335 MPa. The results of the contact angle test showed that the PLLA-Collagen chitosan coating samples were better on hydrophilic properties than the PLLA-Collagen samples. Cytotoxicity test results showed that the percentage of living cells was above 70% thus the membrane was non-toxic.”

PLGA from PolySciTech used in development of inhalable tuberculosis treatment

 


Tuberculosis is a potentially serious infectious disease that mainly affects the lungs. The bacteria that cause tuberculosis are spread from person to person through tiny droplets released into the air via coughs and sneezes. Recently, researchers at Indian Institute of Science used PLGA (cat# AP041) from PolySciTech division of Akina (www.polyscitech.com) to make cationic nanoparticles loaded with rifampicin to target tuberculosis infected mammalian cells. This research holds promise to provide for improved therapies against tuberculosis in the future. Read more: Sharma, Pallavi Raj, Ameya Atul Dravid, Yeswanth Chakravarthy Kalapala, Vishal K. Gupta, Sharumathi Jeyasankar, Avijit Goswami, and Rachit Agarwal. "Cationic inhalable particles for enhanced drug delivery to M. tuberculosis infected macrophages." Biomaterials Advances 133 (2022): 112612. https://www.sciencedirect.com/science/article/pii/S0928493121007529

“Highlights: Mycobacterium tuberculosis infected macrophages are highly phagocytic. Surface charge of PLGA microparticles modified by conjugating poly-l-lysine. Cationic microparticles were taken up rapidly and in large numbers by macrophages. Rifampicin encapsulation in cationic particles improved its intracellular delivery. Enhanced uptake by immune cells and alveolar macrophages in vivo. Abstract: Inhalable microparticle-based drug delivery platforms are being investigated extensively for Tuberculosis (TB) treatment as they offer efficient deposition in lungs and improved pharmacokinetics of the encapsulated cargo. However, the effect of physical parameters of microcarriers on interaction with Mycobacterium tuberculosis (Mtb) infected mammalian cells is underexplored. In this study, we report that Mtb-infected macrophages are highly phagocytic and microparticle surface charge plays a major role in particle internalization by infected cells. Microparticles of different sizes (0.5–2 μm) were internalized in large numbers by Mtb-infected THP-1 macrophages and murine primary Bone Marrow Derived Macrophages in vitro. Drastic improvement in particle uptake was observed with cationic particles in vitro and in mice lungs. Rapid uptake of rifampicin-loaded cationic microparticles allowed high intracellular accumulation of the drug and led to enhanced anti-bacterial function when compared to non-modified rifampicin-loaded microparticles. Cytocompatibility assay and histological analysis in vivo confirmed that the formulations were safe and did not elicit any adverse reaction. Additionally, pulmonary delivery of cationic particles in mice resulted in two-fold higher uptake in resident alveolar macrophages compared to non-modified particles. This study provides a framework for future design of drug carriers to improve delivery of anti-TB drugs inside Mtb-infected cells.”

Wednesday, July 6, 2022

PEG-PCL and PEG-PLA from PolySciTech used to understand protein – block copolymer micelle interactions

 


Block copolymers (PEG-PLGA, PEG-PCL, PEG-PLA, etc.) are commonly used to create drug-delivery platforms as they self-form into micelles which can entrap and carry hydrophobic drugs. Like all chemicals, these structures have a complex interaction with the multitude of components present in human blood which leads to their eventual disruption however exactly 'how' this happens is not well known. Recently, researchers at University of Illinois, Chicago used PEG-PCL (cat# AK073) and PEG-PLA (cat# AK009) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create micelles and investigated their interactions with serum albumins. This research holds promise to provide fundamental understanding to aid in the further development of micelle-based delivery systems. Read more: Dial, Catherine F., and Richard A. Gemeinhart. "Biophysical Characterization of Interactions between Serum Albumin and Block Copolymer Micelles." ACS Biomaterials Science & Engineering (2022). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.2c00016

“Block copolymer micelles have demonstrated great promise in the solubilization of hydrophobic drugs, but an understanding of the blood stability of the drug-laden micelles is needed for therapeutic advancement of micelle technologies. Following intravenous administration, mPEG-CL and mPEG-LA micelles have demonstrated quick release of their cargo and disassembly in blood, but the prevailing mechanisms of micelle disruption and key biomacromolecules driving this disruption have yet to be elucidated. Although protein interactions with solid polymeric nanoparticles have been characterized, not much is known regarding protein interactions with dynamic block copolymer micelles. Herein, we characterize the interaction of bovine and human serum albumins (BSA and HSA) with polymeric micelles, mPEG-CL and mPEG-LA, using protein fluorescence, isothermal titration calorimetry (ITC), and circular dichroism (CD) spectroscopy. We find that BSA and HSA have interactions with mPEG-CL, while only HSA is observed to weakly interact with mPEG-LA. Protein fluorescence suggests that binding of HSA to mPEG-CL and mPEG-LA is driven by electrostatic interactions. ITC suggests an interaction between serum albumin and mPEG-CL block copolymers driven by hydrogen bonding and electrostatic interactions in physiological MOPS-buffered saline, while mPEG-LA has no measurable interaction with either of the serum albumins. CD spectroscopy demonstrates that the protein secondary structure is intact in both proteins in the presence of mPEG-CL and mPEG-LA. Overall, BSA is not always predictive of polymeric interactions with HSA. Understanding of interactions between serum proteins and block copolymer micelles and the exact mechanisms of destabilization will direct the rational design of block copolymer systems for improving blood stability. KEYWORDS: micelle polymer albumin interactions protein−polymer interactions”