Delivery Of Bioactive Molecules Research Articles

DNA-GEL, Novel Nanomaterial for Biomedical Applications and Delivery of Bioactive Molecules

Novel DNA materials promise unpredictable perspectives for applications in cell biology. The realization of DNA-hydrogels built by a controlled association of DNA nanostars, whose binding can be tuned with minor changes in the nucleotide sequences, has been recently described. DNA hydrogels, with specific gelation properties that can be reassambled in desired culture media supplemented with drugs, RNA, DNA molecules and other bioactive compounds offer the opportunity to develop a novel nanomaterial for the delivery of single or multiple drugs in tumor tissues as an innovative and promising strategy. We provide here a comprehensive description of different, recently realized DNA-gels with the perspective of stimulating their biomedical application. Finally, we discuss the possibility to design sophisticated 3D tissue-like DNA-gels incorporating cell spheroids or single cells for the assembly of a novel kind of cellular matrix as a preclinical investigation for the implementation of tools for in vivo delivery of bioactive molecules.

Role of Nanomedicine in Treatment of Brain Cancer

Background: Drug delivery to cancerous brain is a challenging task as it is surrounded by an efficient protective barrier. The main hurdles for delivery of bioactive molecules to cancerous brain are blood brain barrier (BBB), the invasive nature of gliomas, drug resistance, and difficult brain interstitium transportation. Therefore, treatment of brain cancer with the available drug regimen is difficult and has shown little improvement in recent years. Methods: We searched about recent advancements in the use of nanomedicine for effective treatment of the brain cancer. We focused on the use of liposomes, nanoparticles, polymeric micelles, and dendrimers to improve brain cancer therapy. Results: Nanomedicines are well suited for the treatment of brain cancer owing to their highly acceptable biological, chemical, and physical properties. Smaller size of nanomedicines also enhances their anticancer potential and penetration into blood brain barrier (BBB). Conclusion: Recently, nanomedicine based approaches have been developed and investigated for effective treatment of brain cancer. Some of these have been translated into clinical practice, in order to attain therapeutic needs of gliomas. Future advancements in nanomedicines will likely produce significant changes in methods and practice of brain cancer therapy.

Wirelessly triggered bioactive molecule delivery from degradable electroactive polymer films

AbstractThe development of stimuli‐responsive drug delivery systems offers significant opportunities for innovations in industry. It is possible to produce polymer‐based drug delivery devices enabling spatiotemporal control of the release of the drug triggered by an electrical stimulus. Here we describe the development of a wireless controller for drug delivery from conductive/electroactive polymer‐based biomaterials and demonstrate its function in vitro. The wireless polymer conduction controller device uses very low power, operating at 2.4 GHz, and has a supply voltage controller circuit which controls electrical stimulation voltage levels. The computer graphical user interface program communicates with the controller device, and it receives device information, device status and temperature data from the controller device. The prototype of the wireless controller system can trigger the delivery of a drug, dexamethasone phosphate, from a matrix of degradable electroactive polymers. Furthermore, we introduce the application of in silico toxicity screening as a potentially useful method to facilitate the design of non‐toxic degradable electroactive polymers for a multitude of biotechnological applications, addressing one of the key commercial challenges to biomaterial development, in accordance with ‘safe by design’ principles. © 2020 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Functionalized exosome harboring bioactive molecules for cancer therapy.

Exosomes are nanosized vesicles with a lipid membrane that are secreted by most cells and play a crucial role as intermediates of intercellular communication because they carry bioactive molecules. Exosomes are promising for drug delivery of chemicals, proteins, and nucleic acids owing to their inherent properties such as excellent biocompatibility, high tumor targetability, and prolonged circulation in vivo. In this review, we cover recent approaches and advances made in the field of exosome-mediated delivery of bioactive molecules for cancer therapy and factors that affect the clinical use of exosomes. This review can be used as a guideline for further study in expanding the utility of therapeutic exosomes.

Plant-food-derived bioactives: Key health benefits and current nanosystems as a strategy to enhance their bioavailability

Natural products interest is gradually increasing worldwide. Plant-food-derived bioactives have a long history of use as a good source of ingredients for valuable medical usages. Plant-based foods consist of micro and macronutrients, and bioactive components, with health-promoting benefits. The handling of complex mixtures of plants has been methodically switched by therapies using a single isolated substance. The delivery of bioactive molecules in nanosystems is enhancing their bioavailability, it is much safer and cost-effective. However, there are many challenges in combining bioactive substances in nanocarrier materials. A discussion related with nanocarriers will be done in this review.

Lipid Nanostructured Particles as Emerging Carriers for Targeted Delivery of Bioactive Molecules: Applications in Food and Biomedical Sciences (An Overview)

Lipid nanoparticles are getting a growing scientific and technological interest, worldwide. Either Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), Lipid Drug Conjugates (LDCs) or Polymer-Lipid Nanoparticles (PLNs) have been produced and investigated last years, being reccomended as emerging carrier systems for many food and biomedical applications. An overview of the last publications, mainly since 2017 is presented, underlying the most important methods and techniques used for their preparation (e.g. high shear homogenization in hot and cold conditions, ultrasound assisted melt emulsification) as well techniques applied for measuring the size, calorimetric properties, zeta-potential, etc. Most relevant data related to the use of food-grade ingredients and designed lipid nanoparticles as delivery systems for organic and inorganic bioactive molecules in food or packaging’s are presented. The major reason for this trend in food science is the aim to overcome problems associated with the low bioavailability of many lipophilic bioactive compounds which are claimed to bring benefits to human health (carotenoid or anthocyanin pigments, sterols, vitamins). Finally, the recent applications of different formulas of lipid nanoparticles as drug carriers for in vitro experiments or for in vivo therapy (oral, parenteral or transdermal formulas) are presented.

High-throughput, Label-Free Quantitative Proteomic Studies of the Anticancer Effects of Electrical Pulses with Turmeric Silver Nanoparticles: an in vitro Model Study

Triple negative breast cancer (TNBC) represents 15–20% of the over one million new breast cancer cases occurring each year. TNBC is an aggressive cancer phenotype, with low 5-year survival rates, high 3-year recurrence rates, and increased risk of metastasis. A lack of three commonly exploited hormone receptors renders TNBC resistant to endocrine therapies and lends to its critical absence of viable therapeutic targets. This necessitates the development of alternate and effective novel therapeutic strategies for TNBC. Towards this, our current work seeks to develop the technique of Electrical pulse (EP)-mediated Turmeric silver nanoparticles (TurNP) therapy, known as Electrochemotherapy (ECT), to effectively target TNBC cells. This technique involves the efficient delivery of natural bioactive molecules with anti-cancer effects via a biophysical means. In these experiments, the bioactive molecules are turmeric, a dried rhizome of Curcuma longa that has been used for centuries, both as a dietary supplement and as a medicine in Ayurveda (science of life) in the Indian subcontinent and in traditional Chinese medicine. Our results reveal the combined effect of TurNP + EP treatment in reducing MDA-MB-231 cell viability to as low as 9% at 12 h. Showing biological selectivity, this combination treatment has a substantially lower effect on non-tumorigenic mammary epithelial MCF10A cells (67% viability). To gain mechanistic insights into the actions of TurNP-based ECT treatment, we performed high-throughput, label-free quantitative proteomics studies. Proteomics results indicate that TurNP + EP treatment significantly influenced expression of a diverse list of proteins, including receptors, transcription factors, structural proteins, kinases, and metabolic enzymes. This include the downregulation of 25 proteins in PI3K-Akt signaling pathway (such as GRB2, EGFR, EPHA2, GNB1, GNB2, 14–3–3 family, and Integrin family proteins), and 12 proteins (AKR1A1, ALDOA, ALDOC, PGK1, PGM1, PGAM1, ENO1, ENO2, GAPDH, TPI1, LDHA, and LDHB) in the glycolytic pathway with concomitant reduction in metabolite levels (glucose uptake, and intracellular- lactate, glutamine, and glutamate). Compared to TurNP alone, TurNP + EP treatment upregulated 66 endoplasmic reticulum and 193 mitochondrial proteins, enhancing several processes and pathways, including Pyruvate Metabolism, Tricarboxylic acid (TCA) cycle, and Oxidative Phosphorylation (OXPHOS), which redirected the TNBC metabolism to mitochondria. This switch in the metabolism caused excessive production of H2O2 reactive oxygen species (ROS) to inflict cell death in MDA-MB-231 cells, demonstrating the potency of this treatment.

Electrofluidic control of bioactive molecule delivery into soft tissue models based on gelatin methacryloyl hydrogels using threads and surgical sutures

The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100 µA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17 ± 0.50 um/s and took less than 8 minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99 ± 0.40 μm/s) than larger molecules such as dextran (2.26 ± 0.55 μm/s with 4 kDa) or BSA (0.33 ± 0.07 μm/s with 66.5 kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2 hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.

Synthesis and Characterization of a Biocomposite Bone Bandage for Controlled Delivery of Bone-Active Drugs in Fracture Nonunions.

Fracture nonunions are common in orthopedics and their treatment often involves multiple surgical interventions. The aim of this study was to fabricate and characterize a gelatin-nano-hydroxyapatite membrane (GM)-based bone bandage for controlled delivery of bio-active molecules; recombinant human bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) to promote osteoinduction and prevent callus resorption, respectively. In vitro cell-material interaction experiments using MC3T3 cells seeded on the GM indicated good biocompatibility. rhBMP-2-functionalized GM promoted osteogenic differentiation of MC3T3 cells and the rhBMP-2 bio-activity thus remained, as indicated by increased levels of alkaline phosphatase compared to only GM. The GM released a small amount (1.1%) of rhBMP-2 in vitro over a period of 5 weeks, demonstrating a strong interaction of rhBMP-2 with the GM. In the first animal study, the GM specimens loaded with rhBMP-2 or with the combination of rhBMP-2 + ZA were placed in the abdominal muscle pouch of rats. In the GM + rhBMP-2 + ZA group, significantly higher bone volume (21.5 ± 5.9 vs 2.7 ± 1.0 mm3) and area (3.3 ± 2.3 vs 1.0 ± 0.4 mm2) of bone were observed compared to GM + rhBMP-2 after 4 weeks, as indicated by micro-computed tomography and histomorphometry, respectively. Finally, a nonunion model in rats was used to evaluate the efficacy of the GM bandage and bio-active molecules in healing of fracture nonunions. The GM functionalized with rhBMP-2 + ZA led to higher bone formation around the fracture (63.9 ± 19.0 vs 31.8 ± 3.7 mm3) and stronger fracture callus (110.8 ± 46.8 vs 45.6 ± 17.8 N) compared to the empty controls. However, the overall union rate was only marginally improved. The GM alone or combined with ZA did not aid in bone healing in this model. Thus, this study shows that controlled delivery of rhBMP-2 + ZA via the developed GM is a promising approach that could aid in earlier full load bearing in patients with nonunion.

Near‐Infrared Light Triggered‐Release in Deep Brain Regions Using Ultra‐photosensitive Nanovesicles

AbstractRemote and minimally‐invasive modulation of biological systems with light has transformed modern biology and neuroscience. However, light absorption and scattering significantly prevents penetration to deep brain regions. Herein, we describe the use of gold‐coated mechanoresponsive nanovesicles, which consist of liposomes made from the artificial phospholipid Rad‐PC‐Rad as a tool for the delivery of bioactive molecules into brain tissue. Near‐infrared picosecond laser pulses activated the gold‐coating on the surface of nanovesicles, creating nanomechanical stress and leading to near‐complete vesicle cargo release in sub‐seconds. Compared to natural phospholipid liposomes, the photo‐release was possible at 40 times lower laser energy. This high photosensitivity enables photorelease of molecules down to a depth of 4 mm in mouse brain. This promising tool provides a versatile platform to optically release functional molecules to modulate brain circuits.

Multi-stimuli responsive nanogel/hydrogel nanocomposites based on κ-carrageenan for prolonged release of levodopa as model drug

This study describes the development of a novel biocompatible nanogel/hydrogel nanocomposite system for long-term delivery of bioactive molecules. To this aim, the nanogels were synthesized via radical polymerization of poly(N-isopropylacrylamide). The nanogels were introduced during the formation of a hydrogel network to produce nanogel/hydrogel soft nanocomposites, while the biocompatible hydrogel was based on poly (acrylic acid) grafted onto κ-carrageenan polysaccharide with entrapped magnetic iron oxide nanoparticles as crosslinker. In these systems, by using stimuli-responsive functional polymers in both gels (nanogels and hydrogels), pH, thermal and magnetic-responsive properties can be brought to final soft nanocomposites. The obtained soft nanocomposite was characterized by Fourier transform infrared spectrum (FT-IR), thermogravimetric (TG) analysis, and scanning electron microscopy (SEM). This biopolymer based nanogel/hydrogel used as a prolonged releasing drug carrier for levodopa (L-DOPA) as a main drug for treating Parkinson's symptoms. The in vitro release of L-DOPA was investigated at different pHs. pH-dependent release of the active drug can be sustained for >11 days from this soft nanocomposite. The results demonstrated a sustained release model that can be extended for other drugs.

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility.

The Asherman’s syndrome, also known as intrauterine adhesion, often follows endometrium injuries resulting from dilation and curettage, hysteroscopic resection, and myomectomy as well as infection. It often leads to scarring formation and female infertility. Pathological changes mainly include gland atrophy, lack of vascular stromal tissues and hypoxia and anemia microenvironment in the adhesion areas. Surgical intervention, hormone therapy and intrauterine device implantation are the present clinical treatments for Asherman’s syndrome. However, they do not result in functional endometrium recovery or pregnancy rate improvement. Instead, an increasing number of researches have paid attention to the reconstruction of biomimetic endometrium interfaces with advanced tissue engineering technology in recent decades. From micro-scale cell sheet engineering and cell-seeded biological scaffolds to nano-scale extracellular vesicles and bioactive molecule delivery, biomimetic endometrium interfaces not only recreate physiological multi-layered structures but also restore an appropriate nutritional microenvironment by increasing vascularization and reducing immune responses. This review comprehensively discusses the advances in the application of novel biocompatible functionalized endometrium interface scaffolds for uterine tissue regeneration in female infertility.

Kinetic Modeling and Optimization of the Release Mechanism of Curcumin from Folate Conjugated Hybrid BSA Nanocarrier

Abstract Nanocarriers have been explored widely for targeted and sustainable delivery of drugs and other bioactive molecules. Kinetic modeling on the drug release and optimization of the process parameters offers a fundamental explanation for the release mechanism along with an insight on the properties of the carrier. In the present work, a hybrid Bovine serum albumin- Calcium ferrite (BSA-CFNP) nanocarrier in conjugation with folic acid has been developed for the controlled release of curcumin, as a model anticancer drug. Super paramagnetic calcium ferrite nanoparticles were synthesized by sol-gel method. Curcumin was loaded onto the BSA and hybrid BSA-CFNP carriers by desolvation technique. Folic acid conjugation was performed, using EDC coupling reaction, to enable the receptor mediated endocytosis of the drug. The synthesized samples were characterized by FTIR, XRD and SEM techniques. Optimization of curcumin loading on the carrier was evaluated using Taguchi method, which provided a simpler yet effective route to study the influence of the process parameters under consideration. In-vitro stimuli responsive curcumin release studies were investigated. The amount of FA conjugated was also optimized. The drug release trends were studied at different simulated physiological environments. The drug release mechanism was evaluated by applying various kinetic models such as zero order, first order, Higuchi, Korsmeyer Peppas and Hixson Crowell. The controlling parameters and their effects on the release of curcumin from the devised system were elucidated from the best fit model.

Recent advances in natural polymer-based drug delivery systems

Natural polymers have been extensively explored as the vehicles for encapsulation and delivery of drugs and other bioactive molecules, which have attracted tremendous attention. Their inherent advantages in marvelous biocompatibility, controlled enzyme degradation, specific interactions with some biomolecules, and easy modification endow them with versatility in drug delivery. In this perspective, the drug delivery systems (DDS) constructed by representative natural polymers, polysaccharides (chitosan and hyaluronic acid) and proteins (silk fibroin and collagen), are generally summarized. Payloads mainly involve small molecular weight drug, proteins, and DNA for the applications of tissue engineering, wound healing or anticancer therapy. Moreover, the DDS constructed by their derivatives and with other materials also have been presented focusing on the chemical and morphological modifications, the addtions of smart stimuli-triggered or targeted motifs and so on, which evidently promoted the delivery and therapy efficiency. Obviously, more intelligent and specific delivery strategies will be developed and more multifunctional natural polymers based carriers will be expended in the future. We try to seek more insights into the evolution of delivery system so as to figure out what we will truly gain in the next few decades to come.

Role of microsphere as drug carrier for osteogenic differentiation

Drug delivery system in sustainable manner has a great potential in biomedical applications. Along with its biocompatibility, microspheres ability to encapsulate and promote sustained release of drugs or growth factor makes them an ideal carrier for the transport of bioactive molecules for tissue regeneration and controlled drug delivery applications. Additionally, the injectable form of small spherical microsphere facilitates the accurate drug delivery. These drug carrier microspheres have significant role in osteogenic differentiation. The invasive delivery of bioactive molecules promotes bone regeneration. The drug stimulates the osteogenic differentiation of stem cell and promotes the damaged tissue for self-repair. This review elaborates the role of polymeric microspheres and the composite microspheres as a drug carrier for osteogenic differentiation.

Nanocomposites for the delivery of bioactive molecules in tissue repair: vital structural features, application mechanisms, updated progress and future perspectives.

In recent years, nanocomposites have attracted great attention in tissue repair as carriers for bioactive molecule delivery due to their biochemical and nanostructural similarity to that of physiological tissues, and controlled delivery of bioactive molecules. In this review, we aim to comprehensively clarify how the applications of nanocomposites for bioactive molecule delivery in tissue repair are achieved by focusing on the following aspects: (1) vital structural features (size, shape, pore, etc.) of nanocomposites that have crucial effects on the biological properties and function of bioactive molecule-delivery systems, (2) delivery performance of bioactive molecules possessing high entrapment efficiency of bioactive molecules and good controlled- and sustained-release of bioactive molecules, (3) application mechanisms of nanocomposites to deliver and release bioactive molecules in tissue repair, (4) updated research progress of nanocomposites for bioactive molecule delivery in hard and soft tissue repair, and (5) future perspectives in the development of bioactive molecule-delivery systems based on nanocomposites.

Recent advances in polyphenols nanocarriers against breast cancer therapy focus on in vitro studies: literature review

Cancer is considered a severe public health problem worldwide. Among the most incident cases, breast cancer, which affects many women in the entire world, can be mentioned. Currently, there are well-established protocols for the treatment of this type of cancer. However, cancer treatment presents collateral effects that can compromise the patient’s quality of life. Therefore, studies have suggested that plants and fruits rich in polyphenols have antitumor activity, decrease chemotherapy resistance, and reduce side effects caused by chemotherapy. However, most of these compounds have low bioavailability making their potential pharmacological challenging. Therefore, the search for carriers that can efficiently protect and transport these bioatives to tumor cells is of great interest. In this sense, nanostructured systems can be included as the delivery of bioactive molecules and drugs. Thus, this study aimed to report the current studies using nanocarriers containing phenolic compounds to evaluate their antitumor effect against breast cancer cells. Data collection included the virtual databases Science Direct and Web of Science using the descriptors: nanoparticles and polyphenols and breast cancer, for experimental articles published from 2015 to September 15, 2020. The search resulted in a total of 1346 articles, of 37 met the inclusion criteria. The studies have demonstrated the efficiency of nanostructures containing polyphenols against cancer cells, suggesting excellent perspectives in the use of nanotechnology combined with bioactive compounds in the treatment of breast cancer.

A phenotypic approach to probing cellular outcomes using heterobivalent constructs

Various conjugation techniques are used to affect the intracellular delivery of bioactive small molecules. However, the ability to track changes in the phenotype when applying these tools remains poorly studied. We addressed this issue by having prepared a focused library of heterobivalent constructs based on Rho kinase inhibitor HA-100. By comparing the induction of the phenotype of interest, cell viability and cellular uptake, we demonstrate that various conjugates indeed lead to divergent cellular outcomes.

Nanotechnology approaches in the current therapy of skin cancer.

Skin cancer is a high burden disease with a high impact on global health. Conventional therapies have several drawbacks; thus, the development of effective therapies is required. In this context, nanotechnology approaches are an attractive strategy for cancer therapy because they enable the efficient delivery of drugs and other bioactive molecules to target tissues with low toxic effects. In this review, nanotechnological tools for skin cancer will be summarized and discussed. First, pathology and conventional therapies will be presented, followed by the challenges of skin cancer therapy. Then, the main features of developing efficient nanosystems will be discussed, and next, the most commonly used nanoparticles (NPs) described in the literature for skin cancer therapy will be presented. Subsequently, the use of NPs to deliver chemotherapeutics, immune and vaccine molecules and nucleic acids will be reviewed and discussed as will the combination of physical methods and NPs. Finally, multifunctional delivery systems to codeliver anticancer therapeutic agents containing or not surface functionalization will be summarized.

Ethosomes: A Novel Drug Delivery System And Their Therapeutic Applications -A Review

“Ethosomes” are soft vesicles made up of Phospholipids, Ethanol and water. They are “novel carrier system” used for delivery of drugs having low penetration through biological membrane i.e., Skin “Transdermal delivery of drugs” plays a major role in the Ethosomes. In this review we are going to discuss about various applications of ethosomes i.e. Delivery of antibiotic, Delivery of NSAIDS, Anti-cancer, Anti-fungal, Skin cancer, Anti-Acne etc. Ethosomes are loaded with drugs like Indomethacin (NSAIDS), Clotrimazole (Anti-fungal), Raloxifene HCl (Anti-cancer), Fluconazole (Antibiotic) etc. This review explains about the preparation methods used in the preparation of ethosomes such as cold method, Hot method, Injection method, Mechanical dispersion method and Classic methods. Evaluation tests performed in the ethosomes are Drug entrapment efficiency, permeation characteristics, Assay of HPLC, FT-IR studies, stability studies, size analysis, zeta potential etc. Various Penetrtion enhancers like Labrasol, Transcutol, and Terpenes were used in the formulation of ethososmes. Improve the penetration of both lipophilic and hydrophilic drugs through stratum corneum [SC] into deeper layers of the skin very effectively when compared with liposomes. Ethosomes can act as a carrier for large and diverse group of drugs with different physicochemical properties and found a number of applications in pharmaceutical, biotechnological and cosmetic fields. Enhanced delivery of bioactive molecules through the skin and cellular membranes by means of an ethosomal transporter opens numerous confronts and prospects for the research and future development of novel improved therapies. The formulation of ethosomes possesses promising future in effective dermal or transdermal delivery of bioactive agents.