Potential Drug Delivery System Research Articles

Coaxial electrospun nanofibers as drug delivery system for local treatment of periodontitis.

The aim of the present study was to prepare resorbable polylactide fibers for periodontitis treatment using coaxial electrospinning to optimize the release of metronidazole (MNA) by reducing the initial burst effect. Poly(L-lactide-co-D,L-lactide) (PLA) fibers mats with different distributions of metronidazole (MNA) were manufactured by coaxial electrospinning (COAX). By COAX spinning the central core of the fiber was enriched with 40% MNA (m/m), while the sheath of the fiber consisted of PLA only (test group). In contrast, fibers of the control group were prepared by conventional electrospinning with the same amount of MNA but with a homogenous drug distribution (HDD - homogenously distributed drug). The release of MNA was determined by analyzing aliquots from the fiber mats using UV-VIS spectroscopy. Agar diffusion tests were carried out to determine the antibacterial effect on periodontopathogenic bacteria. Biocompatibility was tested in direct contact to human gingival fibroblasts (HGF) for two days. The COAX mats showed a retarded drug release compared to the conventional HDD fibers. After 24h, 64% of total MNA was released cumulatively from the COAX fibers while 90% of the MNA was released from the HDD fibers (controls). The antibacterial effect of COAX fibers was significantly higher after 24h compared to the HDD fibers. Cell cultivation revealed significant higher numbers of vital cells among the COAX mats. COAX fibers showed improved sustained MNA release compared to conventional fibers and can be seen as potential drug delivery systems in local periodontitis treatment.

Amidation of methyl ester-functionalised poly(2-oxazoline)s as a powerful tool to create dual pH- and temperature-responsive polymers as potential drug delivery systems

We present the synthesis of different amine-functionalised poly(2-oxazoline)s, their dual pH and temperature response as well as their capability to as promising stimuli responsive drug delivery vectors.

Biodegradable Polymeric Pharmaceutical Nanoemulgel Coloaded with Eucalyptol‐Lornoxicam: Fabrication and Characterizations for Possible Better Pain Management

Nanoemulgels are considered as potential and ideal drug delivery systems for the transdermal administration of poorly soluble drugs like lornoxicam. Their intrinsic characteristics, such as small globule size as well as excipient type, make transdermal passage of the drug easier. The current study was aimed at developing nanoemulgel based formulation of lornoxicam coloaded with eucalyptol to enhance drug skin permeation and bioavailability in order to promote therapeutic outcome in appropriate time. High shear homogenization technique was utilized to develop optimized lornoxicam encapsulated nanoemulsion followed by its conversion into nanoemulgel formulation by the addition of 1% Carbopol 940 as gelling agent. Different characterization tests were performed on optimized formulation such as surface charge, particle size and size distribution, viscosity, spreadability, pH, drug content determination, drug entrapment efficiency, in vitro drug release, and drug permeation analysis. The optimized formulation had globule size of 143.7 ± 2.18 nm. The results of drug entrapment efficiency, in vitro drug release, and skin penetration experiments were found satisfactory. Based on the formulation type, permeability parameters such as permeability constant (Kp), enhancement ratio (Er), and steady state flux (Jss) revealed greater values and satisfactory outcomes. When compared to other formulations (LRX nanoemulgel and EU nanoemulgel), the LRX‐EU nanoemulgel formulation produced improved skin permeation profile (flux, 189.63 ± 7.68 μg/cm2/h; permeability coefficient, 2.09 ± 0.067 cm/h; and ER, 4.274). This work clearly proved that lornoxicam coloaded with eucalyptol nanoemulgel formulations could be developed to generate stable drug delivery systems. Thus, LRX‐EU NEG formulation seems promising in terms of physicochemical properties, enhanced bioavailability, and high skin penetration profile as compared to LRX NEG formulation.

엔잘루타마이드의 용해도 개선을 위한 고형의 자가나노유화 약물전달시스템

The objective of this study was to develop a novel enzalutamide-loaded solidified self-nanoemulsifying drug delivery system formulation with enhanced solubility and dissolution rate. Various oil and surfactant were screened, then Medium Chain Triglyceride oil and Polysorbate 80 and Labrafil M2125CS were selected as oil and a surfactant. Pseudoternary phase diagram was constructed to detect the nanoemulsion zone. Among the SNEDDS formulations tested, SNEDDS consisted of MCT oil (oil), Polysorbate 80 (surfactant) and Labrafil M2125CS (co-surfactant) at a weight ratio of 20:70:10. The SNEDDS produced the emulsion droplet size 18.66±0.88 nm. Spray drying technique was used to convert the selected enzalutamide-loaded SNEDDS into solid SNEDDS with inert carrier such as silicon dioxide. Enzlautamide-loaded solid SNEDDS was characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffractometry, dynamic light scattering, saturation solubility and in vitro dissolution study. The S-SNEDDS produced an emulsion droplet size of 15.37±0.49 nm and there was no change in particle size between with or without drug. SEM and PXRD results suggested that enzalutamide existed in amorphous form in enzalutamide-loaded solid SNEDDS. In addition, enzalutamide-loaded solid SNEDDS increased saturation solubility 42-fold and dissolution rates 23- fold compared to crystalline enzalutamide. Therefore, the solid SNEDDS could be a potential nano-sized drug delivery system for poorly water-soluble drug enzalutamide.

Reconstructed membrane vesicles from the microalga Dunaliella as a potential drug delivery system

The aim of this biophysical study is to characterize reconstructed membrane vesicles obtained from microalgae in terms of their morphology, properties, composition, and ability to transport a model drug. The reconstructed vesicles were either emptied or non-emptied and exhibited a non-uniform distribution of spherical surface structures that could be associated with surface coat proteins, while in between there were pore-like structures of up to 10 nm that could contribute to permeability. The reconstructed vesicles were very soft and hydrophilic, which could be attributed to their composition. The vesicles were rich in proteins and were mostly derived from the cytoplasm and chloroplasts. We demonstrated that all lipid classes of D. tertiolecta are involved in the formation of the reconstructed membrane vesicles, where they play fundamental role to maintain the vesicle structure. The vesicles appeared to be permeable to calcein, impermeable to FITC-ovalbumin, and semipermeable to FITC-concanavalin A, which may be due to a specific surface interaction with glucose/mannose units that could serve as a basis for the development of drug carriers. Finally, the reconstructed membrane vesicles could pave a new way as sustainable and environmentally friendly marine bioinspired carriers and serve for studies on microtransport of materials and membrane-related processes contributing to advances in life sciences and biotechnology.

Heteroatoms (B, N, S) doped quantum dots as potential drug delivery system for isoniazid: insight from DFT, NCI, and QTAIM

Toxicity in drug includes target toxicity, immune hypersensitivity and off target toxicity. Recently, advances in nanotechnology in the areas of drug delivery have help reduce toxicity and enhance drug solubility and deliver drugs to target sites more efficiently. In this study, we present a novel heteroatom functionalized quantum dot (QD-NBC and QD-NBS) as an effective drug delivery system for isoniazid. The said QD has been computationally modeled to assess its effectiveness in delivering isoniazid to desired target. Density functional theory (DFT) calculations were performed on the QD at the B3LYP/6−311+G(d, p) level to assess its stability through the natural bond orbital (NBO) calculations, and frontier molecular orbital (FMO) before and after interaction with isoniazid drug to understand any change in molecular behavior of the surface. Appropriate intermolecular interactions between the QD and the drug were computed through the Quantum theory of atoms in molecules (QTAIM) and Non-covalent interaction to assess the various binding mechanism and possible interactions resulting to the effective delivery of the drug target. To understand and accurately appraise the binding energy of adsorption, DFT calculations were performed with different functionals (B3LYP, CAM-B3LYP, PBEPBE, GD3BJ & WB97XD/6−311+G (d, p)). The results from DFT calculations point the functionalized QDs to be stable with appreciable energy gap suitable for delivery purposes. The adsorption energy of the drug target with the QD is in the range of −24.73 to 33.75 kcal/mol which indicates substantial interaction of the drug with the QD surface. This absorption energy is comparable with several reported literature and thus prompt the suitability of the surface for isoniazid delivery.

Thiolated pectin-chitosan composites: Potential mucoadhesive drug delivery system with selective cytotoxicity towards colorectal cancer

Mucoadhesive drug delivery systems (DDS) may promote safer chemotherapy for colorectal cancer (CRC) by maximizing local drug distribution and residence time. Carbohydrate polymers, e.g. pectin (P) and chitosan (CS), are potential biomaterials for CRC-targeted DDS due to their gelling ability, mucoadhesive property, colonic digestibility, and anticancer activity. Polymer mucoadhesion is augmentable by thiolation, e.g. pectin to thiolated pectin (TP). Meanwhile, P-CS polyelectrolyte complex has been shown to improve structural stability. Herein, we fabricated, characterized, and evaluated 5-fluorouracil-loaded primary DDS combining TP and CS as a composite (TPCF) through triple crosslinking actions (calcium pectinate, polyelectrolyte complex, disulfide). Combination of these crosslinking yields superior mucoadhesion property relative to single- or dual-crosslinked counterparts, with comparable drug release profile and drug compatibility. PCF and TPCF exhibited targeted cytotoxicity towards HT29 CRC cells with milder cytotoxicity towards HEK293 normal cells. In conclusion, TP-CS composites are promising next-generation mucoadhesive and selectively cytotoxic biomaterials for CRC-targeted DDS.

Improving the circulation time and renal therapeutic potency of extracellular vesicles using an endogenous ligand binding strategy.

Kidney diseases are a serious health issue worldwide, and novel therapeutics are urgently needed. Extracellular vesicles (EVs) have emerged as potent drug delivery systems (DDSs), but their therapeutic potential is limited by short circulation times and insufficient renal retention. Here, we report that endogenous ligand (albumin, ALB) binding is an efficient modification strategy to improve the therapeutic potency of EV-based DDSs for kidney diseases. Surface albumin-binding peptide (ABP)-displayed EVs (ABP-EVs) were produced by transfecting parent cells with the ABP-Lamp2b fusion plasmid. Compared with unmodified EVs (NC-EVs), ABP-EVs showed increased binding to ALB in vitro and elevated circulation time and multiple organ retention in vivo after systemic (iv) injection. Moreover, ABP-EVs had higher renal retention than NC-EVs in mice with acute kidney injury through a complex mechanism involving microvascular injury and megalin-mediated endocytosis. As a result, delivery of small molecule drugs (e.g., curcumin) or proteins (e.g., hepatocyte growth factor) by ABP-EVs had superior therapeutic (e.g., anti-apoptotic, antioxidant, anti-inflammatory) effects in vitro and in vivo. This study highlights that ABP-EVs are versatile DDSs for kidney diseases and provides insights into the new strategies of engineering EVs for drug delivery.

Synergistic chemotherapy and phototherapy based on red blood cell biomimetic nanomaterials.

Novel drug delivery systems (DDSs) have become the mainstay of research in targeted cancer therapy. By combining different therapeutic strategies, potential DDSs and synergistic treatment approaches are needed to effectively deal with evolving drug resistance and the adverse effects of cancer. Nowadays, developing and optimizing human cell-based DDSs has become a new research strategy. Among them, red blood cells can be used as DDSs as they significantly enhance the pharmacokinetics of the transported drug cargo. Phototherapy, as a novel adjuvant in cancer treatment, can be divided into photodynamic therapy and photothermal therapy. Phototherapy using erythropoietic nanocarriers to mimic the unique properties of erythrocytes and overcome the limitations of existing DDSs shows excellent prospects in clinical settings. This review provides an overview of the development of photosensitizers and research on bio-nano-delivery systems based on erythrocytes and erythrocyte membranes that are used in achieving synergistic outcomes during phototherapy/chemotherapy.

Nanoencapsulated nutraceuticals: Potential drug delivery systems for immune health

Nanoencapsulated nutraceuticals: Potential drug delivery systems for immune health

Subcutaneous injection of a bortezomib-loaded thermosensitive hydrogel for the treatment of multiple myeloma

Multiple myeloma (MM) is incurable as one of the most common hematologic malignancies. Bortezomib (BTZ) is a first-in-class reversible proteasome inhibitor in the clinic for the treatment of MM. BTZ was initially approved for the administrator by only the intravenous injection route in 2003. Then, subcutaneous administration was approved in the US and EU in 2012 in addition to the intravenous injection route. The rates and severity of peripheral neuropathy were significantly lower than those of intravenous injection administration. Injectable thermosensitive hydrogels are a potential drug delivery system for controlled release. But it is difficult to achieve the aim of local therapy of MM. A subcutaneous delivery system for a long time may be a potential therapy method due to the subcutaneous administration of BTZ. Here, we designed a BTZ-loaded injectable hydrogel system to sustain drug release for a period of days. It could lower the side effects, enhance the therapeutic effect, and reduce the injection time.

Precision engineering designed phospholipid-tagged pamidronate complex functionalized SNEDDS for the treatment of postmenopausal osteoporosis.

Disodium pamidronate, a second-generation bisphosphonate is a potent drug for the treatment of osteoporosis, which has been very well established by previous literature. It has very low oral permeability, leading to its low oral bioavailability, which restrict this drug to being administered orally. Therefore, the present research work includes the development of an orally effective nanoformulation of pamidronate. In this work, disodium pamidronate was complexed with phospholipon 90G for the enhancement of permeability and to investigate the phospholipon 90G-tagged pamidronate complex-loaded SNEDDS for oral delivery with promises of enhanced bioavailability and anti-osteoporotic activity. The rational design and optimization was employed using Central Composite Design (Design Expert® 12, software) to optimize nanoformulation parameters. In this work, a commercially potential self nano-emulsifying drug delivery system (SNEDDS) has been developed and evaluated for improved oral bioavailability and better clinical acceptance. The hot micro-emulsification and ultracentrifugation method with vortex mixing was utilized for effective tagging of phospholipon 90G with pamidronate and then loading into the SNEDDS nanocarrier. The optimized Pam-PLc SNEDDS formulation was characterized for particle size, PDI, and zeta potential and found to be 56.38 ± 1.37nm, 0.218 ± 0.113, and 22.41 ± 1.14 respectively. Also, a 37.9% improved bioavailability of pamidronate compared to marketed tablet was observed. Similarly, in vivo pharmacokinetic studies suggest a 31.77% increased bone density and significant enhanced bone biomarkers compared to marketed tablets. The developed formulation is safe and effectively overcomes anti-osteoporosis promises with improved therapeutic potential. This work provides very significant achievements in postmenopausal osteoporosis treatment and may lead to possible use of nanotherapeutic-driven emerging biodegradable carriers-based drug delivery.

Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice.

Atractylodes lancea (Thunb.) DC. (A. lancea: AL) is a promising candidate for the treatment of cholangiocarcinoma (bile duct cancer). The study investigated (i) the propensity of capsule formulation of the standardized extract of AL (formulated AL) to modulate mRNA and protein expression and activities of CYP1A2 and CYP3A1 in rats after long- and short-term exposure, (ii) the pharmacokinetics of atractylodin (ATD: active constituent) after long-term administration of formulated AL, and (iii) the biodistribution of atractylodin-loaded polylactic-co-glycolic acid (ATD-PLGA-NPs) in mice. To investigate CYP1A2 and CYP3A1 modulatory activities following long-term exposure, rats of both genders received oral doses of the formulated AL at 1,000 (low dose), 3,000 (medium dose), and 5,000 (high dose) mg/kg body weight daily for 12 months. For short-term effects, male rats were orally administered the formulated AL at the dose of 5,000 mg/kg body weight daily for 1, 7, 14 and 21 days. The pharmacokinetic study was conducted in male rats after administration of the formulated AL at the dose of 5,000 mg/kg body weight daily for 9 months. The biodistribution study was conducted in a male mouse receiving ATD-PLGA-NPs at the equivalent dose to ATD of 100 mg/kg body weight. The high dose of formulated AL produced an inducing effect on CYP1A2 but an inhibitory effect on CYP3A1 activities in male rats. The low dose, however, did not inhibit or induce the activities of both enzymes in male and female rats. ATD reached maximum plasma concentration (Cmax) of 359.73 ng/mL at 3 h (tmax). Mean residence time (MRT) and terminal phase elimination half-life (t1/2z) were 3.03 and 0.56 h, respectively. The extent of biodistribution of ATD in mouse livers receiving ATD-PLGA-NPs was 5-fold of that receiving free ATD. Clinical use of low-dose AL should be considered to avoid potential herb-drug interactions after long-term use. ATD-PLGA-NPs is a potential drug delivery system for cholangiocarcinoma treatment.

Mussel-inspired poly(hydroxyethyl acrylate-co-itaconic acid)-catechol/hyaluronic acid drug-in-adhesive patches for transdermal delivery of ketoprofen

This research aimed to create new hydrophilic drug-in-adhesive patches for transdermal drug delivery. Poly(hydroxyethyl acrylate-co-itaconic acid)-catechol (PHI-cat) and hyaluronic acid (HA) were used as main components in the pressure-sensitive adhesive. Citric acid and aluminium hydroxide were exploited as crosslinking agents and ketoprofen was employed as a model delivering compound. The adhesive performance, physicochemical properties, drug-polymer interaction, drug crystallization, drug content, drug permeation through the skin, and coordination polymer network of the patches were investigated. In addition, skin irritation and adhesion potential in human subjects were assessed. Due to the ability of catechol groups to form interaction with the skin tissue, the patches containing PHI-cat and HA offered a considerably greater adhesion ability to human skin compared with the patches without catechol and commercial patches. Furthermore, the patches had good physical and chemical stability. Therefore, these catechol-functionalized patches may be potential transdermal drug delivery systems with excellent adhesive properties for the delivery of a drug through the skin.

Ethylferulate-loaded nanoemulsions as a novel anti-inflammatory approach for topical application

Ethyl ferulate (EF) is a phenylpropanoid with antioxidant and anti-inflammatory activities extracted from essential oil of several plants. However, this compound is immiscible with water. In this study, different nanoemulsion (NE) formulations were prepared and have their physicochemical properties assessed to induce a stable and efficient aqueous colloidal dispersion of drug. The oil-in-water NE samples were selected from the pseudo-ternary phase diagram constructed using soybean oil as oily phase, and a mixture of surfactants composed by polysorbate 80 and sorbitan monooleate. The oil phase containing surfactants was mixed with water using a ultrasonication procedure at 25 °C. The formulation with the smallest and uniformly droplet-sized have the ethyl ferulate-loading in three concentrations (1 %, 2.5 %, and 5 % w/w). Their interactions with compounds of NE were followed using Fourier transform infrared spectroscopy. The samples exhibited an incredible physical stability, even after drug-loading. The NE showed the ability for controlling the drug release. The in vivo experiments with rats demonstrated the biocompatibility of tested formulations, no skin irritation signs were identified. In addition, an efficient reducing of paw edema was observed compared to the used control. The experimental achievements suggest an interesting and promising novel ethyl ferulate nanoemulsion, as a potential drug delivery system to be used for topical anti-inflammatory application.

Isopropyl Amino Acid Esters Ionic Liquids as Vehicles for Non-Steroidal Anti-Inflammatory Drugs in Potential Topical Drug Delivery Systems with Antimicrobial Activity.

New derivatives of non-steroidal anti-inflammatory drugs were synthesized via conjugation with L-amino acid isopropyl esters. The characteristics of the physicochemical properties of the obtained pharmaceutically active ionic liquids were determined. It has been shown how the incorporation of various L-amino acid esters as an ion pair affects the properties of the parent drug. Moreover, the antimicrobial activity of the obtained compounds was evaluated. The proposed structural modifications of commonly used drugs indicate great potential for use in topical and transdermal preparations.

Free‐Blockage Mesoporous Silica Nanoparticles Loaded with Cerium Oxide as ROS‐Responsive and ROS‐Scavenging Nanomedicine (Adv. Funct. Mater. 46/2022)

Mesoporous Materials In article number 2208316, Xiaohui Ju and co-workers report the design of free-blockage reactive oxygen species (ROS)-responsive mesoporous silica nanoparticles (MSNs) as potential drug delivery systems. Methyl sulfide units are functionalized onto MSNs through co-condensation or grafting pathways. In an ROS-rich environment, the nanocarriers undergo structure and polarity changes and release cargo of cerium oxide nanoparticles to scavenge excessive ROS related to pathological conditions.

Redox-responsive hydrogels of thiolated pectin as vehicles for the smart release of acetaminophen

Redox-responsive hydrogels gained considerable attention as drug delivery systems since they allow releasing of encapsulated drugs under specific conditions. The potentialities of these smart materials can increase considerably with the use of biopolymers; however, this option is barely investigated. In this study, we report an original strategy for the synthesis of a polysaccharide-based hydrogel consisting only of thiolated pectin and exploited it as a potential drug delivery system with redox-responsive properties. Hydrogels of different compositions were synthesized by disulfide crosslinking using a simple one-pot process without additional chemical catalysts. Beyond the complete characterization, we demonstrate that the synthesized hydrogels were quickly degraded in the presence of physiological reducing agents (L-glutathione and L-cysteine), whereas exhibiting high stability in their absence. Acetaminophen (a model drug) was encapsulated into these hydrogels and further released in the absence and presence of reducing agents. These experiments confirmed the redox-responsiveness of the synthesized materials, which can be ranked as an advantage for smart drug release devices.

Effect of ionic strength on porosity and surface charge of chitosan nanoparticles

Chitosan, a natural cationic polymer, is gaining popularity due to its biodegradable and biocompatible properties. The parameters such as ionic strength (I) and porosity play an important role in case of chitosan nanoparticles (CSNPs) contributing to their formation, stability, and suitable biomedical applications. To explore these findings, we varied the concentration of acetic acid (I) and studied physicochemical properties of CSNPs, which revealed the effect of ionic strength on the surface properties and porosity of CSNPs. Further, ionic strength of CSNPs simulated using COMSOL Multiphysics. Thus, our conclusions give important understanding on the applicability of CSNPs as a potential drug delivery system for future applications.

Hybrid Lipid Nanoparticles Loaded with Doxorubicin for the Therapy of Breast Cancer

Breast cancer is the leading cause of death in women and its incidence is growing fast worldwide. Due to the poor benefits of doxorubicin (Dox), the first line chemotherapeutic drug for breast cancer treatment, the development of new drug delivery systems (DDSs) for Dox is critical to improve the breast cancer treatment efficacy. Here in this study, we used a film dispersion method to construct hybrid lipid nanoparticles (HLN) containing different lipids, including biotin conjugated lipid, during which Dox was loaded into the carrier to finally construct Dox loaded HLN (HLN/Dox) as a potential DDS for targeted breast cancer therapy. Our results showed that HLN/Dox were nanosized formulation with increased accumulation to MCF-7 cells due to biotin modification both in vitro and in vivo . In addition, the cellular cytotoxicity as well we in vivo antitumor assay also showed the promising cancer cell killing and tumor inhibition effects of HLN/Dox, which suggested its potential to be applied in future clinical practice.