Complexos polieletrólitos de quitosana e xantana carregados com ativos naturais e sintéticos: estudo físico/químico e microbiológico para aplicação de drug delivery / Polyelectrolyte complexes of chitosan and xanthan loaded with natural and synthetic actives: physicochemical and microbiological study for drug delivery application

A eficácia dos implantes osseointegrados é amplamente reconhecida na literatura científica. Contudo, infiltrações bacterianas na junção implante-pilar podem desencadear inflamação nos tecidos circundantes, contribuindo para a evolução de condições mais sérias, como a peri-implantite. O objetivo desse estudo foi produzir complexos polieletrólitos (PECs) de quitosana (Q) e xantana (X) em forma de membranas, carregá-las com ativos naturais e sintéticos antimicrobianos, caracterizálas estruturalmente e avaliá-las frente a degradação enzimática, cinética de liberação e ações antimicrobianas com finalidade de aplicação para drug delivery. Membranas de QX a 1% (m/v) foram produzidas em três proporções, totalizando doze grupos experimentais: QX (1:1); QX (1:2), QX (2:1), QX-P (com própolis) (1:1); QX-P (1:2); QX-P (2:1); QX-C (com canela) (1:1); QX-C (1:2); QX-C (2:1) e CLX (com clorexidina 0,2%) (1:1); CLX (1:2); CLX (2:1). Para os estudos de caracterização foram feitas análises da espessura em estado seco; análises morfológicas superficial e transversal em Microscopia Eletrônica de Varredura (MEV); análise estrutural de espectroscopia de infravermelho por transformada de Fourier (FTIR); análise de degradação por perda de massa sob ação da enzima lisozima; e análise da cinética de liberação dos ativos em saliva artificial. Para os testes microbiológicos, análises de verificação de halo de inibição e ação antibiofilme foram feitas contra cepas de Staphylococcus aureus (S. aureus) e Escherichia coli (E. coli). Os resultados demonstraram que a espessura das membranas variou conforme a proporção, sendo que o grupo QX (1:2) apresentou a maior média de 1,022 mm ± 0,2, seguida respectivamente do QX (1:1) com 0,641 mm ± 0,1 e QX (2:1) com 0,249 mm ± 0,1. Nas imagens de MEV é possível observar uma maior presença de fibras, rugosidade e porosidade nos grupos QX (1:2) e QX (1:1) respectivamente, e, no QX (2:1) uma superfície mais lisa, uniforme e fina. No FTIR foram confirmados os picos característicos dos materiais isoladamente, além de observar as ligações iônicas que ocorreram para formação dos PECs. Na análise de degradação, os grupos com ativos naturais adicionados tiveram melhores taxas de sobrevida do que os grupos QX. No teste de liberação, os grupos QX-P tiveram uma cinética mais lenta que os QX-C, cuja liberação acumulada de 100% foi feita em 24 h. Já nos testes do halo inibitório, somente os grupos CLX tiveram ação sobre as duas cepas, e os QX-P tiveram sobre S. aureus. Nas análises antibiofilme, os grupos CLX apresentaram as maiores taxas de redução metabólica nas duas cepas (± 79%); os grupos QX-P apresentaram taxas de redução similares em ambas as cepas, porém com percentual um pouco maior para E. coli (60- 80%) e os grupos QX-C tiveram grande discrepância entre as duas cepas: de 35 a 70% para S. aureus e 14 a 19% para E. coli. Pode-se concluir que, frente as análises feitas, o comportamento do material foi afetado diretamente pelos ativos adicionados a matriz polimérica. As proporções de Q ou X afetaram somente a espessura final. Quanto a aplicação proposta de drug delivery, os dispositivos apresentaram grande potencial, principalmente os grupos CLX e QX-P. (AU)

The effectiveness of osseointegrated implants is widely recognized in scientific literature. However, bacterial infiltrations at the implant-abutment interface may trigger inflammation in surrounding tissues, contributing to the development of more serious conditions, such as peri-implantitis. The aim of this study was to produce chitosan (Q) and xanthan (X) polyelectrolyte complexes (PECs) in the form of membranes, load and evaluate them for enzymatic degradation, release kinetics, and antimicrobial actions for drug delivery applications. QX membranes at 1% (w/v) were produced in three proportions, totaling twelve experimental groups: QX (1:1), QX (1:2), QX (2:1), QX-P (with propolis) (1:1), QX-P (1:2), QX-P (2:1), QX-C (with cinnamon) (1:1), QX-C (1:2), QX-C (2:1), and CLX (with 0.2% chlorhexidine) (1:1), CLX (1:2), CLX (2:1). Characterization studies included analyses of dry state thickness, surface and crosssectional morphology using Scanning Electron Microscopy (SEM), structural analysis by Fourier Transform Infrared (FTIR) spectroscopy, mass loss degradation analysis under lysozyme action, and active release kinetics analysis in artificial saliva. Microbiological tests included verification analyses of inhibition halos and antibiofilm action against strains of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Results showed that membrane thickness varied according to proportion, with group QX (1:2) presenting the highest average of 1.022 mm ± 0.2, followed by QX (1:1) with 0.641 mm ± 0.1, and QX (2:1) with 0.249 mm ± 0.1. SEM images showed greater presence of fibers, roughness, and porosity in groups QX (1:2) and QX (1:1) respectively, while QX (2:1) exhibited a smoother, more uniform, and thinner surface. FTIR confirmed characteristic peaks of the materials individually, besides showing ionic bonds formed for PECs. Degradation analysis revealed that groups with added natural actives had better survival rates than QX groups. In release tests, QX-P groups exhibited slower kinetics than QX-C, with 100% cumulative release achieved in 24 h. inhibitory halo tests, only CLX groups exhibited action against both strains, while QX-P acted against S. aureus. Antibiofilm analyses showed CLX groups with the highest metabolic reduction rates in both strains (± 79%); QX-P groups showed similar reduction rates in both strains, slightly higher for E. coli (60-80%), and QX-C groups had a significant discrepancy between strains: 35-70% for S. aureus and 14-19% for E. coli. In conclusion, material behavior was directly affected by added actives to the polymeric matrix. Proportions of Q or X only affected final thickness. Regarding proposed drug delivery applications, the devices showed great potential, especially CLX and QX-P groups.(AU)

Estudo da encapsulação de fármacos antineoplásicos em sistemas nanoestruturados: Caracterização estrutural e efeito sinérgico de fármacos / Study of the encapsulation of antineoplastic drugs in nanostructured systems: Structured characterization and synergistic effect of drugs

Dentro da área da nanotecnologia, o sistema drug delivery vem sendo amplamente utilizado, cujo objetivo é proporcionar uma maior eficácia dos ativos farmacêuticos, podendo envolver desde uma distribuição mais seletiva dentro do organismo até a taxa que as moléculas serão liberadas e/ou a atenuação dos efeitos adversos provocados. Para isso, os ativos são encapsulados em nanoestruturas, podendo estas serem de natureza sintética ou natural. Dentre os nanocarreadores promissores encontram-se os cubossomos, que são nanoestruturas complexas capazes de encapsular ativos tanto hidrofílicos quanto hidrofóbicos. O objetivo deste projeto foi estudar a encapsulação de fármacos antineoplásicos em sistemas drug delivery contra linhagens celulares, investigando também as alterações estruturais sofridas pelos cubossomos e os efeitos sinérgicos dos fármacos, sendo eles: a doxorrubicina, a cisplatina, a vemurafenibe e a curcumina. As metodologias empregadas para elucidar o efeito das combinações dos fármacos, a estruturação da nanopartícula e sua citotoxicidade foram: os estudos de viabilidade celular pós-exposição, espalhamento dinâmico de luz, potencial zeta, análise de rastreamento de nanopartículas, espalhamento de raios-x a baixos ângulos, criomicroscopia eletrônica de transmissão, eficiência de encapsulação e ensaio de liberação. Inicialmente os fármacos foram testados isoladamente e em duplas, sendo utilizadas cinco linhagens celulares, afim de se promover um delineamento aos ensaios futuros. A partir destes resultados, foi-se optado por manter duas linhagens celulares, a HeLa, como representante de tecidos tumorais, e a HaCat, modelo de tecido saudável, devido a menor resistência apresentada por elas. Em relação as combinações entre as drogas, pode-se observar que todas as duplas formadas apresentaram resultados sinérgicos na linhagem tumoral, sendo mantida para os testes seguintes a combinação curcumina e vemurafenibe. Os cubossomos foram sintetizados eficientemente, sendo produzidos na ausência de fármacos bem como contendo curcumina e vemurafenibe. As nanopartículas apresentaram uma variação de diâmetro entre 189 ± 3 nm e 224 ± 2 nm, sendo o PDI entre 0,08 e 0,25. A conformação do cubossomo foi confirmada através da criomicroscopia eletrônica de transmissão e pelo espalhamento de raios-x a baixos ângulos, onde foi determinada uma estruturação característica de Pn3m. Para a eficiência de encapsulação os valores variaram entre 79% de encapsulação para a curcumina e 72% para a vemurafenibe, quando utilizadas isoladamente. No caso da encapsulação em dupla, os valores se converteram para 63% e 53% para a curcumina e vemurafenibe, respectivamente. A liberação das drogas do interior da nanopartícula oscilou entre 1500, 480 e 420 minutos para os cubossomos de curcumina, vemurafenibe e curcumina + vemunafenibe, respectivamente. Os testes de citotoxicidade demonstraram que as concentrações de 0,01 e 0,03 mg/mL foram capazes de promover uma viabilidade acima de 70%, porém, utilizando estas proporções não foi possível observar resultados significativos. Por fim, o sistema se mostrou estável e homogêneo, sendo capaz de promover a encapsulação dos fármacos tanto singularmente quanto em dupla e, apesar da quantidade de fármacos não ter sido suficiente para ocasionar alterações ao sistema celular, a execução deste trabalho abre portas para que novos estudos sejam realizados, podendo-se testar diferentes ativos bem como alterando a composição da nanopartícula afim de se reduzir a citotoxicidade

Within the area of nanotechnology, the drug delivery system has been widely used, whose objective is to provide greater effectiveness of pharmaceutical active ingredients, which may range from a more selective distribution within the organism to the rate at which the molecules will be released and/or the attenuation of adverse effects caused. To achieve this, the active ingredients are encapsulated in nanostructures, which may be synthetic or natural in nature. Among the promising nanocarriers are cubosomes, which are complex nanostructures capable of encapsulating both hydrophilic and hydrophobic active ingredients. The objective of this project was to study the encapsulation of antineoplastic drugs in drug delivery systems against cell lines, also investigating the structural changes undergone by the cubosomes and the synergistic effects ofthe drugs, namely: doxorubicin, cisplatin, vemurafenib and curcumin. The methodologies used to elucidate the effect of drug combinations, the structuring of the nanoparticle and its cytotoxicity were: post-exposure cell viability studies, dynamic light scattering, zeta potential, nanoparticle tracking analysis, small angle x-rays scattering, transmission electron cryomicroscopy, encapsulation efficiency and release assay. Initially, the drugs were tested alone and in pairs, using five cell lines, in order to promote a design for future trials. Based on these results, it was decided to maintain two cell lines, HeLa, as a representative oftumor tissues, and HaCat, a model ofhealthy tissue, due to their lower resistance. Regarding the combinations between the drugs, it can be observed that all the pairs formed presented synergistic results in the tumor lineage, with the combination of curcumin and vemurafenib being maintained for the following tests. Cubosomes were efficiently synthesized, being produced in the absence of drugs as well as containing curcumin and vemurafenib. The nanoparticles varied in diameter between 189 ± 3 nm and 224 ± 2 nm, with the PDI being between 0.08 and 0.25. The conformation ofthe cubosome was confirmed through transmission electron cryomicroscopy and small angle x-rays scattering, where a characteristic structure of Pn3m was determined. For encapsulation efficiency, values varied between 79% encapsulation for curcumin and 72% for vemurafenib, when used alone. ln the case of double encapsulation, the values converted to 63% and 53% for curcumin and vemurafenib, respectively. The release of drugs from the interior of the nanoparticle ranged between 1500, 480 and 420 minutes for the curcumin, vemurafenib and cubosomes with curcumin + vemunafenib, respectively. Cytotoxicity tests demonstrated that concentrations of 0.01 and 0.03 mg/mL were capable of promoting viability above 70%, however, using these proportions it was not possible to observe significant results. Finally, the system proved to be stable and homogeneous, being able to promote the encapsulation of drugs both singly and in pairs and, although the quantity of drugs was not enough to cause changes to the cellular system, the execution of this work opens doors for new studies are carried out, with the possibility oftesting different active ingredients as well as changing the composition of the nanoparticle in order to reduce cytotoxicity

Development, characterization and anti - Mycobacterium tuberculosis activity of solid lipid nanoparticles for oral Piper corcovadensis roots extract delivery / Desarrollo, caracterización y actividad anti - Mycobacterium tuberculosis de nanopartículas lipídicas sólidas para la administración oral de extracto de raíces de Piper corcovadensis

The present study thus aimed at the development and physicochemical characterization of solid lipid nanoparticles loaded with crude extract of Piper corcovadensis roots (SLN - CEPc) and chitosan - coated solid lipid nanoparticles loaded with crude extract of P. corcovadensis roots (C - SLN - CEPc), as well as the determination of its antimycobacterial activity against Mycobacterium tuberculosis H37Rv, its cytotoxicity against the Vero cell line and evaluation in the hemolysis assay. Both formulat ions containing the encapsulated extract showed high encapsulation efficiency, formed by a monodispersed system with small and spherical particles, and there was no aggregation of particles. In the biological assays, SLN - CEPc and C - SLN - CEPc showed promisin g anti - M. tuberculosis activity with a minimum inhibitory concentration (MIC) of 12.5 µg/mL, whereas the cytotoxic concentrations obtained at 50% (CC 50 ) in Vero cells were 60.0 and 70.0 µg/mL, respectively. Therefore, nanoencapsulation showed satisfactory results, justifying its usage in the development of new products.

El presente estudio apuntó al desarrollo y caracterización fisicoquímica de na nopartículas lípidas en estado sólido, cargadas con extracto crudo de raíz de Piper c orcovadensis (SLN - CEPc) y nanopartículas lípidas en estado sólido cubiertas con quitosano cargadas co n extracto crudo de raíz de P. corcovadensis (C - SLN - CEPc), así como la determinación de su actividad antimico bacterial contra Mycobacterium tuberculosis H37Rv, su citotoxicidad contra la línea celular Vero y su evaluación en ensayo de hemólisis. Ambas formulaciones que contenían el extracto encapsulado mostraron alta eficien cia de encapsulación, formado por un sistema monodispersado con pequeñas partículas esféricas, y no hubo agregación de partículas. En los ensayos biológicos, SLN - CEPc y C - SLN - CEPc mostraron un a prometedora actividad anti - M. tuberculosis con una mínima conc entración inhibitoria (MIC) de 12,5 µg/mL, mientras que las concentraciones citotóxicas obtenidas al 50% (CC 50 ) en células Vero estuvo en 60,0 y 70,0 µg/mL, respectivamente. Por lo tanto, la nanoencapsulación mostró resultados satisfactorios, justificando su uso en el desarrollo de nuevos productos.

Effect of polymer nanoparticles on atherosclerotic lesions and the associated mechanisms: a review / 生物工程学报

Polymer nanoparticles generally refer to hydrophobic polymers-based nanoparticles, which have been extensively studied in the nanomedicine field due to their good biocompatibility, efficient long-circulation characteristics, and superior metabolic discharge patterns over other nanoparticles. Existing studies have proved that polymer nanoparticles possess unique advantages in the diagnosis and treatment of cardiovascular diseases, and have been transformed from basic researches to clinical applications, especially in the diagnosis and treatment of atherosclerosis (AS). However, the inflammatory reaction induced by polymer nanoparticles would induce the formation of foam cells and autophagy of macrophages. In addition, the variations in the mechanical microenvironment of cardiovascular diseases may cause the enrichment of polymer nanoparticles. These could possibly promote the occurrence and development of AS. Herein, this review summarized the recent application of polymer nanoparticles in the diagnosis and treatment of AS, as well as the relationship between polymer nanoparticles and AS and the associated mechanism, with the aim to facilitate the development of novel nanodrugs for the treatment of AS.

Erythrocytes-camouflaged nanoparticles: a promising delivery system for drugs and vaccines / 生物工程学报

Erythrocytes-camouflaged nanoparticles is an in vivo delivery system that uses erythrocytes or erythrocyte membrane nano vesicles as carriers for drugs, enzymes, peptides and antigens. This system has the advantages of good biocompatibility, long circulation cycle and efficient targeting. This review summarizes the type of carriers, their development history, the application of delivery strategies as well as their limitations and future challenges. Lastly, future directions and key issues in the development of this system are discussed.

Application of self-assembly in polypeptide drugs: a review / 生物工程学报

Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.

Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review / 中国中药杂志

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis / 中国中药杂志

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

Progress in preparation and application of sodium alginate microspheres / 生物医学工程学杂志

Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage capacity. The formation condition of sodium alginate gel is mild, effectively avoiding the inactivation of active substances. After a variety of preparation methods, sodium alginate microspheres are widely used in the fields of biomaterials and tissue engineering. This paper reviewed the common methods of preparing alginate microspheres, including extrusion, emulsification, electrostatic spraying, spray drying and coaxial airflow, and discussed their applications in biomedical fields such as bone repair, hemostasis and drug delivery.

Advances in modification and delivery of nucleic acid drugs / 浙江大学学报·医学版

Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.

Application of organic nanocarriers for intraocular drug delivery / 浙江大学学报·医学版

The application of intraocular drug delivery is usually limited due to special anatomical and physiological barriers, and the elimination mechanisms in the eye. Organic nano-drug delivery carriers exhibit excellent adhesion, permeability, targeted modification and controlled release abilities to overcome the obstacles and improve the efficiency of drug delivery and bioavailability. Solid lipid nanoparticles can entrap the active components in the lipid structure to improve the stability of drugs and reduce the production cost. Liposomes can transport hydrophobic or hydrophilic molecules, including small molecules, proteins and nucleic acids. Compared with linear macromolecules, dendrimers have a regular structure and well-defined molecular mass and size, which can precisely control the molecular shape and functional groups. Degradable polymer materials endow nano-delivery systems a variety of size, potential, morphology and other characteristics, which enable controlled release of drugs and are easy to modify with a variety of ligands and functional molecules. Organic biomimetic nanocarriers are highly optimized through evolution of natural particles, showing better biocompatibility and lower toxicity. In this article, we summarize the advantages of organic nanocarriers in overcoming multiple barriers and improving the bioavailability of drugs, and highlight the latest research progresses on the application of organic nanocarriers for treatment of ocular diseases.

Research progress on the nucleoside/nucleotide-loaded nanomedicines / 浙江大学学报·医学版

Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.

Advances in anti-invasive fungal drug delivery systems / 浙江大学学报·医学版

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.

Factors affecting nasal drug delivery and design strategies for intranasal drug delivery / 浙江大学学报·医学版

Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.

Drug target inference by mining transcriptional data using a novel graph convolutional network framework

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.

Progresses on active targeting liposome drug delivery systems for tumor therapy / 生物医学工程学杂志

Liposome is an ideal drug carrier with many advantages such as excellent biocompatibility, non-immunogenicity, and easy functionalization, and has been used for the clinical treatment of many diseases including tumors. For the treatment of tumors, liposome has some passive targeting capability, but the passive targeting effect alone is very limited in improving the drug enrichment in tumor tissues, and active targeting is an effective strategy to improve the drug enrichment. Therefore, active targeting liposome drug-carriers have been extensively studied for decades. In this paper, we review the research progresses on active targeting liposome drug-carriers based on the specific binding of the carriers to the surface of tumor cells, and summarize the opportunities, challenges and future prospects in this field.

Research progress of extracellular vesicles in the treatment of renal disease / 生理学报

Extracellular vesicles (EVs) are lipid bilayer-enclosed structures containing diverse bioactive cargoes that play a major role in intercellular communication in both physiological and pathological conditions. Currently, the field of EV-based therapy has been rapidly growing, and two main therapeutic uses of EVs can be surmised: (i) exploiting stem cell-derived EVs as therapeutic agents; and (ii) employing EVs as natural therapeutic vectors for drug delivery. This review will discuss the recent advances in EV-based therapy in the treatment of renal disease.

Peptide-based bioactivated in vivo assembly nanomaterials and its biomedical applications: a review / 生物工程学报

Based on the self-assembly process occurring in the human body all the time, self-assembled nanomaterials were designed by the researchers. The self-assembled nanomaterials have controllability, biocompatibility and functional advantages in vivo. The self-assembled nanomaterials constructed in situ under a physiological environment display various biological characteristics which can be used for imaging, therapy, and broad clinical applications. In situ self-assembled nanomaterials can boost drug function, reduce toxic and side effects, prolong imaging time and enlarge signal-to-noise ratio. By using pathological conditions to trigger specific responses in vivo, well-ordered nanoaggregates can be spontaneously formed by multiple weak bonding interactions. The assembly shows higher accumulation and longer retention in situ. Endogenous triggers for in situ assembly, such as enzymes, pH, reactive oxygen species and ligand receptor interaction, can be used to transform the materials into a variety of controllable nanostructures including nanoparticles, nanofibers and gels through bioactivated in vivo assembly (BIVA) strategies. BIVA strategies can be applied for treatment, imaging or participate in the physiological activities of cells at the lesion site. This review summarized and prospected the design of self-assembled peptide materials based on BIVA technology and their biomedical applications. The nanostructures of the self-assembly enable some beneficial biological effects, such as assembly induced retention (AIR) effect, enhanced targeting effect, multivalent bond effect, and membrane disturbance. Thus, the BIVA nanotechnology is promising for efficient drug delivery, enhancement of targeting and treatment, as well as optimization of the biological distribution of drugs.

Optimization of Diltiazem hydrochloride osmotic formulation using QBD approach

Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.