scholarly journals Nanotherapeutics for neurosurgically-applied drug delivery

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv15-iv16
Author(s):  
Catherine Vasey ◽  
Vincenzo Taresco ◽  
Stuart Smith ◽  
Cameron Alexander ◽  
Ruman Rahman
Keyword(s):  
Ring Opening ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Residual Tumour ◽  
Tumour Burden ◽  
Functional Capability ◽  
Tumour Heterogeneity ◽  
Self Assembling ◽  
Cavity Boundary ◽  
Future Work

Abstract Despite multimodal treatment, the median survival of Glioblastoma multiforme (GBM) 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. Based on an increasing understanding of GBM intra-tumour heterogeneity, the capability to deliver multiple therapeutic moieties from single formulations is clinically-relevant. It is hypothesised that incorporating drug-loaded polymer pro-drugs, which are capable of transcytotic ‘hopping’, into a biodegradable microparticulate paste will lead to efficacious local delivery. Here we report the formulation of numerous self-assembling cytocompatible nanoparticles, based on different linear and branched polymeric architectures. The polymers were synthesised by ring opening polymerisation with organic catalysts, leading to controlled reaction kinetics and greater potential biomedical applicability. We demonstrated that copolymerisation of a monomer with functional capability enabled the successful conjugation of doxorubicin to the polymer chain. 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. We will discuss strategies to incorporate: i) pH-sensitive linkers to the polymeric backbone, which would allow controlled drug release in acidic microenvironments; ii) multiple combined chemotherapeutics, including doxorubicin and olaparib. Future work will assess the efficacy of the polymer pro-drugs against primary GBM lines derived from the invasive margin and safety/efficacy using orthotopic syngeneic allografts. This is the first study incorporating polymer pro-drugs of this type into an existing localised micro-scale delivery system for GBM therapies.

scholarly journals EXTH-69. NANOTHERAPEUTICS FOR NEUROSURGICALLY-APPLIED DRUG DELIVERY

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.

scholarly journals ATRP-based synthesis of a pH-sensitive amphiphilic block polymer and its self-assembled micelles with hollow mesoporous silica as DOX carriers for controlled drug release

RSC Advances ◽  
2021 ◽  
Vol 11 (48) ◽  
pp. 29986-29996
Author(s):  
Xiuxiu Qi ◽  
Hongmei Yan ◽  
Yingxue Li
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Self Assembly ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Ph Sensitive ◽  
Core Shell ◽  
Assembly Process ◽  
Block Polymer ◽  
Hollow Mesoporous Silica

A pH-sensitive core–shell nanoparticle (HMS@C18@PSDMA-b-POEGMA) was developed via a self-assembly process as the carrier of anticancer drug doxorubicin (DOX) for drug loading and controlled release.

scholarly journals Amorphous Drug-Polymer Salts

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1271
Author(s):  
Xin Yao ◽  
Amy Lan Neusaenger ◽  
Lian Yu
Keyword(s):  
Recent Progress ◽  
Drug Loading ◽  
Salt Formation ◽  
High Drug ◽  
Coated Particles ◽  
Tropical Conditions ◽  
Amorphous Drugs ◽  
Amorphous Drug ◽  
Future Work ◽  
High Drug Loading

Amorphous formulations provide a general approach to improving the solubility and bioavailability of drugs. Amorphous medicines for global health should resist crystallization under the stressful tropical conditions (high temperature and humidity) and often require high drug loading. We discuss the recent progress in employing drug–polymer salts to meet these goals. Through local salt formation, an ultra-thin polyelectrolyte coating can form on the surface of amorphous drugs, immobilizing interfacial molecules and inhibiting fast crystal growth at the surface. The coated particles show improved wetting and dissolution. By forming an amorphous drug–polymer salt throughout the bulk, stability can be vastly enhanced against crystallization under tropical conditions without sacrificing the dissolution rate. Examples of these approaches are given, along with suggestions for future work.

scholarly journals Advances in Polyhydroxyalkanoate Nanocarriers for Effective Drug Delivery: An Overview and Challenges

Nanomaterials ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 175
Author(s):  
Priyanka Prakash ◽  
Wing-Hin Lee ◽  
Ching-Yee Loo ◽  
Hau Seung Jeremy Wong ◽  
Thaigarajan Parumasivam
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
In Situ Polymerization ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Production Costs ◽  
Natural Polymers ◽  
High Production ◽  
The Many

Polyhydroxyalkanoates (PHAs) are natural polymers produced under specific conditions by certain organisms, primarily bacteria, as a source of energy. These up-and-coming bioplastics are an undeniable asset in enhancing the effectiveness of drug delivery systems, which demand characteristics like non-immunogenicity, a sustained and controlled drug release, targeted delivery, as well as a high drug loading capacity. Given their biocompatibility, biodegradability, modifiability, and compatibility with hydrophobic drugs, PHAs often provide a superior alternative to free drug therapy or treatments using other polymeric nanocarriers. The many formulation methods of existing PHA nanocarriers, such as emulsion solvent evaporation, nanoprecipitation, dialysis, and in situ polymerization, are explained in this review. Due to their flexibility that allows for a vessel tailormade to its intended application, PHA nanocarriers have found their place in diverse therapy options like anticancer and anti-infective treatments, which are among the applications of PHA nanocarriers discussed in this article. Despite their many positive attributes, the advancement of PHA nanocarriers to clinical trials of drug delivery applications has been stunted due to the polymers’ natural hydrophobicity, controversial production materials, and high production costs, among others. These challenges are explored in this review, alongside their existing solutions and alternatives.

scholarly journals Thiophene Derivatives as Anticancer Agents and Their Delivery to Tumor Cells Using Albumin Nanoparticles

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 192 ◽  
Author(s):  
Guangsheng Cai ◽  
Simiao Wang ◽  
Lang Zhao ◽  
Yating Sun ◽  
Dongsheng Yang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Drug Loading ◽  
Great Promise ◽  
Self Assembling ◽  
Laser Confocal Scanning Microscopy ◽  
Confocal Scanning ◽  
Thiophene Derivatives

A series of thiophene derivatives (TPs) were synthesized and evaluated for cytotoxicity in HepG2 and SMMC-7721 cell lines by MTT assay. TP 5 was identified as a potential anticancer agent based on its ability to inhibit tumor cell growth. Drawbacks of TPs, including poor solubility and high toxicity, were overcome through delivery using self-assembling HSA nanoparticles (NPs). The optimum conditions for TP 5-NPs synthesis obtained by adjusting the temperature and concentration of TP 5. The NPs had an encapsulation efficiency of 99.59% and drug-loading capacity of 3.70%. TP 5 was slowly released from TP 5-NPs in vitro over 120 h. HepG2 and SMMC-7721 cell lines were employed to study cytotoxicity of TP 5-NPs, which exhibited high potency. ROS levels were elevated and mitochondrial membrane potentials reversed when the two cell lines were treated with TP 5-NPs for 12 h. Cellular uptake of fluorescence-labeled TP 5-NPs in vitro was analyzed by flow cytometry and laser confocal scanning microscopy. Fluorescence intensity increased over time, suggesting that TP 5-NPs were efficiently taken up by tumor cells. In conclusion, TP 5-NPs showed great promise as an anticancer therapeutic agent.

Pseudolatex from STR 5L Block Rubber for Drug Delivery

2013 ◽  
Vol 844 ◽  
pp. 166-169 ◽  
Author(s):  
Prapaporn Boonme ◽  
Kamon Panrat ◽  
Wiwat Pichayakorn
Keyword(s):  
Drug Release ◽  
Contact Allergy ◽  
Drug Loading ◽  
Methyl Cellulose ◽  
Controlled Drug Release ◽  
Colloidal Dispersion ◽  
Mineral Oil ◽  
Lauryl Sulfate ◽  
Drug Encapsulation

Pseudolatex is colloidal dispersion containing spherical solid or semisolid particles and can be prepared from any existing thermoplastic water-insoluble polymers. It is useful for drug encapsulation and controlled drug release. In this study, pseudolatex base was prepared from STR 5L block rubber. The various parameters such as speed and time of homogenization, type and concentration of surfactants, amount of mineral oil, and type of drug loading were studied to prepare the stable pseudolatex. These preparations were evaluated in particle size, pH, viscosity, emulsion stability, drug encapsulation, and in vitro drug release. It was found that the most stable formulation contained 3.5% block rubber, 0.2% methyl cellulose, 6% mineral oil, 4% dibutyl phthalate, 2% sodium lauryl sulfate, and 2% Uniphen P-23 using the speed and time of homogenizer as 20000 rpm and 20 minutes, respectively. Furthermore, the pseudolatex bases reduced the protein impurity form 0.5516% to 0.2108% in formulation with mineral oil and to 0.1781% in formulation without mineral oil, that could decrease contact allergy caused by the protein allergens. Dichloromethane residues in pseudolatex bases were 22.05 mg/L and 7.85 mg/L in formulations with and without mineral oil, respectively, that were satisfied from USP recommendation value of lower than 600 mg/L. Propranolol HCl, lidocaine HCl, and indomethacin could be loaded into pseudolatex only in the concentration of 1%. However, lidocaine base in the concentration of 1-5% could be loaded into pseudolatex which had the similar physical properties and stability to pseudolatex base. The in vitro drug release from pseudolatexs provided the controlled drug release for more than 24 hr.

Micelles with Cyclic Poly(ε-caprolactone) Moieties: Greater Stability, Larger Drug Loading Capacity, and Slower Degradation Property for Controlled Drug Release

Langmuir ◽  
2019 ◽  
Vol 35 (38) ◽  
pp. 12509-12517 ◽  
Author(s):  
Guiying Kang ◽  
Lu Sun ◽  
Yuping Liu ◽  
Chao Meng ◽  
Wei Ma ◽  
...  
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Loading Capacity

scholarly journals Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance

2015 ◽  
Vol 112 (10) ◽  
pp. 2978-2983 ◽  
Author(s):  
Tuo Wei ◽  
Chao Chen ◽  
Juan Liu ◽  
Cheng Liu ◽  
Paola Posocco ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Therapy ◽  
Drug Delivery System ◽  
Anticancer Drug ◽  
Delivery System ◽  
Drug Carrier ◽  
Drug Loading ◽  
Cancer Drug ◽  
Self Assembling

Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy.

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