Retinol-Containing Graft Copolymers for Delivery of Skin-Curing Agents

The new polymeric systems for delivery in cosmetology applications were prepared using self-assembling amphiphilic graft copolymers. The synthesis based on “click” chemistry reaction included grafting of azide-functionalized polyethylene glycol (PEG-N3) onto multifunctional polymethacrylates containing alkyne units. The latter ones were obtained via atom transfer radical polymerization (ATRP) of alkyne-functionalized monomers, e.g., ester of hexynoic acid and 2-hydroxyethyl methacrylate (AlHEMA) with methyl methacrylate (MMA), using bromoester-modified retinol (RETBr) as the initiator. Varying the content of alkyne moieties adjusted by initial monomer ratios of AlHEMA/MMA was advantageous for the achievement of a well-defined grafting degree. The designed amphiphilic graft copolymers P((HEMA-graft-PEG)-co-MMA), showing tendency to micellization in aqueous solution at room temperature, were encapsulated with arbutin (ARB) or vitamin C (VitC) with high efficiencies (>50%). In vitro experiments carried out in the phosphate-buffered saline solution (PBS) at pH 7.4 indicated the maximum release of ARB after at least 20 min and VitC within 10 min. The fast release of the selected antioxidants and skin-lightening agents by these micellar systems is satisfactory for applications in cosmetology, where they can be used as the components of masks, creams, and wraps.

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EXTH-69. NANOTHERAPEUTICS FOR NEUROSURGICALLY-APPLIED DRUG DELIVERY

Neuro-Oncology ◽

10.1093/neuonc/noz175.399 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi96-vi97

Author(s):

Catherine Vasey ◽

Vincenzo Taresco ◽

Stuart Smith ◽

Cameron Alexander ◽

Ruman Rahman

Keyword(s):

Drug Loading ◽

Controlled Drug Release ◽

Glioma Cell Line ◽

Residual Tumour ◽

Drug Nanoparticles ◽

Self Assembling ◽

Post Surgery ◽

Primary Cell Lines ◽

Initial Monomer

Abstract Despite multimodal treatment, the median survival of Glioblastoma multiforme (GBM) patients remains less than 15 months, in considerable part due to diffusely infiltrative disease. Better treatment methods are necessary to eradicate residual tumour burden remaining beyond the resection cavity boundary. It is hypothesised that incorporating drug-loaded polymer pro-drug nanoparticles into a biodegradable microparticulate paste will lead to efficacious local delivery. We report the formulation of numerous self-assembling cytocompatible nanoparticles, based on different linear and branched polymeric architectures, amenable for localised intra-cavity delivery post-surgery. The polymers were synthesised by ring-opening polymerisation with organic catalysts, leading to controlled reaction kinetics and greater potential biomedical applicability. A simple nanoprecipitation technique was employed to gain nanoparticles with the size range of 60–130 nm, depending on the initial monomer ratios and polymeric architectures. Successful biocompatibility studies of the self-assembling nanoparticles have been carried out in vitro on the U87 glioma cell line. We demonstrated that copolymerisation of a monomer with functional capability enabled the successful conjugation of doxorubicin to the polymer chain. We will discuss strategies to incorporate pH-sensitive linkers to the polymeric backbone, which would allow controlled drug release in acidic microenvironments. Based on an increasing understanding of GBM intra-tumour heterogeneity, the capability to deliver multiple therapeutic moieties from single formulations is clinically-relevant. Thus, we hypothesised that polymers with a greater degree of branching over traditional linear structures would lead to greater drug loading, and successfully tested this hypothesis through the encapsulation of olaparib. Future work will assess the efficacy of the polymer pro-drug nanoparticles against both commercial and primary cell lines, and safety/efficacy of intra-cavity delivery using orthotopic syngeneic allografts, thus giving a more therapeutically-relevant insight into the activity of the formulations. This is the first study incorporating polymer pro-drugs of this type into an existing localised micro-scale delivery system for GBM therapies.

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Micellar Carriers Based on Amphiphilic PEG/PCL Graft Copolymers for Delivery of Active Substances

Polymers ◽

10.3390/polym12122876 ◽

2020 ◽

Vol 12 (12) ◽

pp. 2876 ◽

Cited By ~ 1

Author(s):

Justyna Odrobińska ◽

Dorota Neugebauer

Keyword(s):

Molecular Weight ◽

Graft Copolymers ◽

Drug Loading ◽

Polymer System ◽

Amphiphilic Copolymers ◽

Bioactive Substances ◽

Click Reactions ◽

Micellar Systems ◽

Active Substances

Amphiphilic copolymers of alkyne functionalized 2-hydroxyethyl methacrylate (AlHEMA) and poly(ethylene glycol) methyl ether methacrylate (MPEGMA) with graft or V-shaped graft topologies were synthesized. The functionalization of poly(ε-caprolactone) (PCL) with azide group enabled attachment to P(AlHEMA-co-MPEGMA) copolymers via a “click” alkyne-azide reaction. The introduction of PCL as a second side chain type in addition to PEG resulted in heterografted copolymers with modified properties such as biodegradability. “Click” reactions were carried out with efficiencies between 17–70% or 32–50% (for lower molecular weight PCL, 4000 g/mol, or higher molecular weight PCL, 9000 g/mol, respectively) depending on the PEG grafting density. The graft copolymers were self-assembled into micellar superstructures with the ability to encapsulate active substances, such as vitamin C (VitC), arbutin (ARB) or 4-n-butylresorcinol (4nBRE). Drug loading contents (DLC) were obtained in the range of 5–55% (VitC), 39–91% (ARB) and 42–98% (4nBRE). In vitro studies carried out in a phosphate buffer saline (PBS) solution (at pH 7.4 or 5.5) gave the maximum release levels of active substances after 10–240 min depending on the polymer system. Permeation tests in Franz chambers indicated that the bioactive substances after release by micellar systems penetrated through the artificial skin membrane in small amounts, and a majority of the bioactive substances remained inside the membrane, which is satisfactory for most cosmetic applications.

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4-n-Butylresorcinol-Based Linear and Graft Polymethacrylates for Arbutin and Vitamins Delivery by Micellar Systems

Polymers ◽

10.3390/polym12020330 ◽

2020 ◽

Vol 12 (2) ◽

pp. 330 ◽

Cited By ~ 3

Author(s):

Justyna Odrobińska ◽

Łukasz Mielańczyk ◽

Dorota Neugebauer

Keyword(s):

Click Reaction ◽

Skin Condition ◽

Amphiphilic Copolymers ◽

Solution Ph ◽

Polymeric Systems ◽

Micellar Systems ◽

Poly Ethylene ◽

Positive Effect ◽

Active Substances

A novel initiator, bromoester modified 4-n-butylresorcinol (4nBREBr2), was prepared and utilized in controlled atom transfer radical polymerization (ATRP) to obtain three series of amphiphilic copolymers. The V-shaped copolymers of methyl methacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA), and poly(ethylene glycol) methyl ether methacrylate (MPEGMA), abbreviated to P(HEMA–co–MMA), P(HEMA–co–MPEGMA), and P(MMA–co–MPEGMA), were synthesized. Moreover, P((HEMA–graft–PEG)–co–MMA) graft copolymers were prepared by combining the pre-polymerization modification of HEMA and a “click” reaction using a “grafting onto” approach. All copolymers could form micelles with encapsulated active substances (vitamin C (VitC), vitamin E (VitE), arbutin (ARB)), which are used in cosmetology. In vitro studies carried out in a PBS solution (pH 7.4) demonstrates that in most cases the maximum release of active substance was after 1 h. The polymeric systems presenting satisfactory encapsulation characteristics and release profiles are attractive micellar carriers of cosmetic substances, which show a positive effect on the skin condition.

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Synthesis and Characterization of Ionic Graft Copolymers: Introduction and In Vitro Release of Antibacterial Drug by Anion Exchange

Polymers ◽

10.3390/polym12092159 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2159

Author(s):

Katarzyna Niesyto ◽

Dorota Neugebauer

Keyword(s):

Bacterial Infections ◽

Graft Copolymers ◽

In Vitro Release ◽

Water Soluble ◽

Antibacterial Drug ◽

Water Contact ◽

Drug Conjugates ◽

Self Assembling ◽

Grafting From

Amphiphilic graft copolymers based on [2-(methacryloyloxy)ethyl]trimethyl- ammonium chloride (TMAMA) were obtained for the delivery of pharmaceutical ionic drugs, such as p-aminosalicylate (PAS) and clavunate (CLV) anions. The side chains were attached by grafting from a multifunctional macroinitiator via atom transfer radical polymerization (ATRP) to get polymers with different grafting degrees and ionic content. The self-assembling ability, confirmed by determining the critical micelle concentration (CMC) through interfacial tension (IFT) with the use of goniometry, was reduced after ion exchange (CMC twice higher than for chloride anions contained copolymers 0.005–0.026 mg/mL). Similarly, the hydrophilicity level (adjusted by the content of ionic fraction) evaluated by the water contact angle (WCA) of the polymer film surfaces was decreased with the increase of trimethylammonium units (68°–44°) and after introduction of pharmaceutical anions. The exchange of Cl− onto PAS− and CLV− in the polymer matrix was yielded at 31%–64% and 79%–100%, respectively. The exchange onto phosphate anions to release the drug was carried out (PAS: 20%–42%, 3.1–8.8 μg/mL; CLV: 25%–73%, 11–31 μg/mL from 1 mg of drug conjugates). Because of the bacteriostatic activity of PAS and the support of the action of the antibiotics by CLV, the designed water-soluble systems could be alternatives for the treatment of bacterial infections, including pneumonia and tuberculosis.

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Torus Circumference and Thickness Parameters From a Linear DNA Size Series Suggest How Toruses Self-Assemble

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119430 ◽

1985 ◽

Vol 43 ◽

pp. 522-523

Author(s):

George C. Ruben ◽

Kenneth A. Marx

Keyword(s):

Tertiary Structure ◽

Dna Complexes ◽

Tertiary Structures ◽

Self Assembling ◽

Double Stranded Dna ◽

Calf Thymus ◽

Dna Organization ◽

Condensed Dna ◽

Dna Size

Certain double stranded DNA bacteriophage and viruses are thought to have their DNA organized into large torus shaped structures. Morphologically, these poorly understood biological DNA tertiary structures resemble spermidine-condensed DNA complexes formed in vitro in the total absence of other macromolecules normally synthesized by the pathogens for the purpose of their own DNA packaging. Therefore, we have studied the tertiary structure of these self-assembling torus shaped spermidine- DNA complexes in a series of reports. Using freeze-etch, low Pt-C metal (10-15Å) replicas, we have visualized the microscopic DNA organization of both calf Thymus( CT) and linear 0X-174 RFII DNA toruses. In these structures DNA is circumferentially wound, continuously, around the torus into a semi-crystalline, hexagonal packed array of parallel DNA helix sections.

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Effect of temperature, CO2 and O2 on motility and mobility of Anisakidae larvae

Scientific Reports ◽

10.1038/s41598-021-83505-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aiyan Guan ◽

Inge Van Damme ◽

Frank Devlieghere ◽

Sarah Gabriël

Keyword(s):

Enzymatic Digestion ◽

Infected Fish ◽

Effect Of Temperature ◽

Video Recordings ◽

Different Temperatures ◽

Semi Solid ◽

Zoonotic Parasites ◽

The Impact ◽

Phosphate Buffered Saline

AbstractAnisakidae, marine nematodes, are underrecognized fish-borne zoonotic parasites. Studies on factors that could trigger parasites to actively migrate out of the fish are very limited. The objective of this study was to assess the impact of different environmental conditions (temperature, CO2 and O2) on larval motility (in situ movement) and mobility (migration) in vitro. Larvae were collected by candling or enzymatic digestion from infected fish, identified morphologically and confirmed molecularly. Individual larvae were transferred to a semi-solid Phosphate Buffered Saline agar, and subjected to different temperatures (6 ℃, 12 ℃, 22 ℃, 37 ℃) at air conditions. Moreover, different combinations of CO2 and O2 with N2 as filler were tested, at both 6 °C and 12 °C. Video recordings of larvae were translated into scores for larval motility and mobility. Results showed that temperature had significant influence on larval movements, with the highest motility and mobility observed at 22 ℃ for Anisakis spp. larvae and 37 ℃ for Pseudoterranova spp. larvae. During the first 10 min, the median migration of Anisakis spp. larvae was 10 cm at 22 ℃, and the median migration of Pseudoterranova spp. larvae was 3 cm at 37 ℃. Larval mobility was not significantly different under the different CO2 or O2 conditions at 6 °C and 12 ℃. It was concluded that temperature significantly facilitated larval movement with the optimum temperature being different for Anisakis spp. and Pseudoterranova spp., while CO2 and O2 did not on the short term. This should be further validated in parasite-infected/spiked fish fillets.

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Amphiphilic Graft Copolymers Capable of Mixed-Mode Interaction as Alternative Nonviral Transfection Agents

ACS Applied Bio Materials ◽

10.1021/acsabm.0c01123 ◽

2021 ◽

Vol 4 (2) ◽

pp. 1268-1282

Author(s):

Ivonne L. Diaz Ariza ◽

Valérie Jérôme ◽

León D. Pérez Pérez ◽

Ruth Freitag

Keyword(s):

Mixed Mode ◽

Graft Copolymers ◽

Mode Interaction ◽

Amphiphilic Graft Copolymers ◽

Nonviral Transfection

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Characterization of Gelatin Hydrogels Cross-Linked with Microbial Transglutaminase as Engineered Skeletal Muscle Substrates

Bioengineering ◽

10.3390/bioengineering8010006 ◽

2021 ◽

Vol 8 (1) ◽

pp. 6

Author(s):

Divya Gupta ◽

Jeffrey W. Santoso ◽

Megan L. McCain

Keyword(s):

Skeletal Muscle ◽

Elastic Modulus ◽

Ambient Air ◽

In Vitro Models ◽

Microbial Transglutaminase ◽

Conventional Culture ◽

Muscle Tissues ◽

Physical Features ◽

Phosphate Buffered Saline

Engineered in vitro models of skeletal muscle are essential for efficiently screening drug safety and efficacy. However, conventional culture substrates poorly replicate physical features of native muscle and do not support long-term culture, which limits tissue maturity. Micromolded gelatin hydrogels cross-linked with microbial transglutaminase (gelatin-MTG hydrogels) have previously been shown to induce C21C2 myotube alignment and improve culture longevity. However, several properties of gelatin-MTG hydrogels have not been systematically characterized, such as changes in elastic modulus during incubation in culture-like conditions and their ability to support sarcomere maturation. In this study, various gelatin-MTG hydrogels were fabricated and incubated in ambient or culture-like conditions. Elastic modulus, mass, and transmittance were measured over a one- or two-week period. Compared to hydrogels in phosphate buffered saline (PBS) or ambient air, hydrogels in Dulbecco’s Modified Eagle Medium (DMEM) and 5% CO2 demonstrated the most stable elastic modulus. A subset of gelatin-MTG hydrogels was micromolded and seeded with C2C12 or primary chick myoblasts, which aligned and fused into multinucleated myotubes with relatively mature sarcomeres. These data are important for fabricating gelatin-MTG hydrogels with predictable and stable mechanical properties and highlight their advantages as culture substrates for engineering relatively mature and stable muscle tissues.

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The Antibacterial Effects of Resin-Based Dental Sealants: A Systematic Review of In Vitro Studies

Materials ◽

10.3390/ma14020413 ◽

2021 ◽

Vol 14 (2) ◽

pp. 413

Author(s):

Saad Saeed AlShahrani ◽

Mana’a Saleh AlAbbas ◽

Isadora Martini Garcia ◽

Maha Ibrahim AlGhannam ◽

Muath Abdulrahman AlRuwaili ◽

...

Keyword(s):

Antibacterial Agents ◽

Data Extraction ◽

Risk Of Bias ◽

Dental Sealants ◽

Medium Risk ◽

Metabolic Activities ◽

High Degree ◽

Phosphate Buffered Saline ◽

Full Text Screening

This review aimed to assess the antimicrobial effects of different antibacterial agents/compounds incorporated in resin-based dental sealants. Four databases (PubMed, MEDLINE, Web of Science and Scopus) were searched. From the 8052 records retrieved, 275 records were considered eligible for full-text screening. Nineteen studies met the inclusion criteria. Data extraction and quality assessment was performed by two independent reviewers. Six of the nineteen included studies were judged to have low risk of bias, and the rest had medium risk of bias. Compounds and particles such as zinc, tin, Selenium, chitosan, chlorhexidine, fluoride and methyl methacrylate were found to be effective in reducing the colony-forming unit counts, producing inhibition zones, reducing the optical density, reducing the metabolic activities, reducing the lactic acid and polysaccharide production and neutralizing the pH when they are added to the resin-based dental sealants. In addition, some studies showed that the antibacterial effect was not significantly different after 2 weeks, 2 months and 6 months aging in distilled water or phosphate-buffered saline. In conclusion, studies have confirmed the effectiveness of adding antibacterial agents/compounds to dental sealants. However, we should consider that these results are based on laboratory studies with a high degree of heterogeneity.

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Dermal delivery of amitriptyline for topical analgesia

Drug Delivery and Translational Research ◽

10.1007/s13346-021-00982-x ◽

2021 ◽

Author(s):

Chin-Ping Kung ◽

Bruno C. Sil ◽

Yanling Zhang ◽

Jonathan Hadgraft ◽

Majella E. Lane ◽

...

Keyword(s):

Treatment Options ◽

Isopropyl Myristate ◽

Promising Candidate ◽

In Vitro Permeation ◽

Base Form ◽

Dermal Delivery ◽

Phosphate Buffered Saline ◽

Topical Analgesia ◽

Topical Analgesic

Abstract Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical properties of the molecule, amitriptyline is also a promising candidate for delivery as a topical analgesic. Here we report the dermal delivery of amitriptyline from a range of simple formulations. The first stage of the work required the conversion of amitriptyline hydrochloride to the free base form as confirmed by nuclear magnetic resonance (NMR). Distribution coefficient values were measured at pH 6, 6.5, 7, and 7.4. Solubility and stability of amitriptyline were assessed prior to conducting in vitro permeation and mass balance studies. The compound demonstrated instability in phosphate-buffered saline (PBS) dependent on pH. Volatile formulations comprising of isopropyl alcohol (IPA) and isopropyl myristate (IPM) or propylene glycol (PG) were evaluated in porcine skin under finite dose conditions. Compared with neat IPM, the IPM:IPA vehicles promoted 8-fold and 5-fold increases in the amount of amitriptyline that permeated at 24 h. Formulations containing PG also appear to be promising vehicles for dermal delivery of amitriptyline, typically delivering higher amounts of amitriptyline than the IPM:IPA vehicles. The results reported here suggest that further optimization of topical amitriptyline formulations should be pursued towards development of a product for clinical investigational studies. Graphical abstract

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