Design Of Drug Delivery Systems Research Articles

A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy.

Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms. In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS). In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells. This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

Fast dissolving tablet

Fast dissolving tablets have emerged as a popular dosage form, particularly beneficial for pediatric and geriatric patients facing challenges such as dysphagia or hand tremors. These tablets dissolve quickly in saliva without needing water, enhancing compliance and effectiveness of therapy. They offer advantages like easy portability, accurate dosing, and improved bioavailability. Various technologies, including spray drying and melt granulation, have been developed for their manufacturing. This review provides comprehensive information on fast dissolving tablets, covering their definition, advantages, limitations, challenges, and available formulations. The design of an oral drug delivery system prioritizes convenience in administration and improved patient compliance, making it the preferred route of drug delivery despite certain drawbacks. Over the last decade, there has been a growing demand for Fast Disintegrating Tablets (FDTS), turning this field into a rapidly expanding area within the pharmaceutical industry. The formulation’s popularity and effectiveness have led to the development of various FDT technologies. These technologies aim to achieve rapid tablet disintegration and mouth dissolution within five seconds, eliminating the need for chewing or water intake. This characteristic is particularly advantageous for populations such as pediatrics, geriatrics, and patients facing difficulties in swallowing conventional tablets and capsules. The formulation of an easily administrable dosage form, considering challenges like swallowing difficulties and low patient compliance, has driven the creation of orally disintegrating tablets. Traditional preparation methods include spray drying, freeze drying, direct compression, molding, and sublimation. In addition, new technologies have been devised to enhance the production of orodispersible tablets.

Dynamic Simulations of Interaction of the PEG-DPPE Micelle-Encapsulated Short-Chain Ceramides with the Raft-Included Membrane.

The lipid raft subdomains in cancer cell membranes play a key role in signal transduction, biomolecule recruitment, and drug transmembrane transport. Augmented membrane rigidity due to the formation of a lipid raft is unfavorable for the entry of drugs, a limiting factor in clinical oncology. The short-chain ceramide (CER) has been reported to promote drug entry into membranes and disrupt lipid raft formation, but the underlying mechanism is not well understood. We recently explored the carrier-membrane fusion dynamics of PEG-DPPE micelles in delivering doxorubicin (DOX). Based on the phase-segregated membrane model composed of DPPC/DIPC/CHOL/GM1/PIP2, we aim to explore the dynamic mechanism of the PEG-DPPE micelle-encapsulating DOXs in association with the raft-included cell membrane modulated by C8 acyl tail CERs. The results show that the lipid raft remains integrated and DOX-resistant subjected to free DOXs and the micelle-encapsulating ones. Addition of CERs disorganizes the lipid raft by pushing CHOL aside from DPPC. It subsequently allows for a good permeability for PEG-DPPE micelle-encapsulated DOXs, which penetrate deeper as CER concentration increases. GM1 is significant in guiding drugs' redistributing between bilayer phases, and the anionic PIP2 further helps DOXs attain the inner bilayer surface. These results elaborate on the perturbing effect of CERs on lipid raft stability, which provides a new comprehensive approach for further design of drug delivery systems.

Rational design of a nonclassical liposomal nanoscale drug delivery system for innovative cancer therapy

AbstractAdvanced drug delivery systems are widely considered to be powerful approaches for treating cancer and many other diseases because of their superior ability to improve pharmacokinetics, promote lesion‐targeted delivery efficacy, and/or reduce the toxic effects of diverse therapeutics. Owing to the unique biomimetic structure of lipid bilayers surrounding aqueous cavities, liposomes have been found to encapsulate various therapeutics, ranging from small molecules with different hydrophobicities to biomacromolecules. With the advent of surface PEGylation, stealth liposomes with excellent in vivo long‐circulating behaviors have been generated, thus these liposomes have been extensively explored for the development of liposomal drugs with greatly improved in vivo pharmacokinetic behaviors by functioning as delivery vehicles. Inspired by their successes in clinical practice, stealth liposomes have recently been utilized as the main building scaffold or surface coating layers of other nanoparticulate formulations, which are coined as nonclassical liposomal nanoscale drug delivery systems (NDDSs) in this review, to enable the rational design of next‐generation liposomal nanomedicine. Therefore, after overviewing the latest progress in the development of conventional liposome‐based nanomedicine, we will introduce the development of these nonclassical liposomal NDDSs as well as their innovative cancer treatment strategies. We will subsequently provide a critical perspective on the future development of new cancer nanomedicines based on these rationally designed nonclassical liposomal NDDSs.

Modular Synthesis of PEG-Dendritic Block Copolymers by Thermal Azide-Alkyne Cycloaddition with Internal Alkynes and Evaluation of their Self-Assembly for Drug Delivery Applications.

Linear-dendritic block copolymers assemble in solution due to differences in the solubility or charge properties of the blocks. The monodispersity and multivalency of the dendritic block provide unparalleled control for the design of drug delivery systems when incorporating poly(ethylene glycol) (PEG) as a linear block. An accelerated synthesis of PEG-dendritic block copolymers based on the click and green chemistry pillars is described. The tandem composed of the thermal azide-alkyne cycloaddition with internal alkynes and azide substitution is revealed as a flexible, reliable, atom-economical, and user-friendly strategy for the synthesis and functionalization of biodegradable (polyester) PEG-dendritic block copolymers. The high orthogonality of the sequence has been exploited for the preparation of heterolayered copolymers with terminal alkenes and alkynes, which are amenable for subsequent functionalization by thiol-ene and thiol-yne click reactions. Copolymers with tunable solubility and charge were so obtained for the preparation of various types of nanoassemblies with promising applications in drug delivery.

Enhancing Drug Delivery Efficacy Through Bilayer Coating of Zirconium-Based Metal-Organic Frameworks: Sustained Release and Improved Chemical Stability and Cellular Uptake for Cancer Therapy.

The development of nanoparticle (NP)-based drug carriers has presented an exciting opportunity to address challenges in oncology. Among the 100,000 available possibilities, zirconium-based metal-organic frameworks (MOFs) have emerged as promising candidates in biomedical applications. Zr-MOFs can be easily synthesized as small-size NPs compatible with intravenous injection, whereas the ease of decorating their external surfaces with functional groups allows for targeted treatment. Despite these benefits, Zr-MOFs suffer degradation and aggregation in real, in vivo conditions, whereas the loaded drugs will suffer the burst effect-i.e., the fast release of drugs in less than 48 h. To tackle these issues, we developed a simple but effective bilayer coating strategy in a generic, two-step process. In this work, bilayer-coated MOF NU-901 remained well dispersed in biologically relevant fluids such as buffers and cell growth media. Additionally, the coating enhances the long-term stability of drug-loaded MOFs in water by simultaneously preventing sustained leakage of the drug and aggregation of the MOF particles. We evaluated our materials for the encapsulation and transport of pemetrexed, the standard-of-care chemotherapy in mesothelioma. The bilayer coating allowed for a slowed release of pemetrexed over 7 days, superior to the typical 48 h release found in bare MOFs. This slow release and the related performance were studied in vitro using both A549 lung cancer and 3T mesothelioma cells. Using high-resolution microscopy, we found the successful uptake of bilayer-coated MOFs by the cells with an accumulation in the lysosomes. The pemetrex-loaded NU-901 was indeed cytotoxic to 3T and A549 cancer cells. Finally, we demonstrated the general approach by extending the coating strategy using two additional lipids and four surfactants. This research highlights how a simple yet effective bilayer coating provides new insights into the design of promising MOF-based drug delivery systems.

Advancing Bone-Targeted Drug Delivery: Leveraging Biological Factors and Nanoparticle Designs to Improve Therapeutic Efficacy.

Designing targeted drug delivery systems to effectively treat bone diseases ranging from osteoporosis to nonunion bone defects remains a significant challenge. Previously, nanoparticles (NPs) self-assembled from diblock copolymers of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (PSMA-b-PS) delivering a Wnt agonist were shown to effectively target bone and improve healing via the introduction of a peptide with high affinity to tartrate-resistant acid phosphatase (TRAP), an enzyme deposited by the osteoclasts during bone remodeling. Despite these promising results, the underlying biological factors governing targeting and subsequent drug delivery system (DDS) design parameters have not been examined to enable the rational design to improve bone selectivity. Therefore, this work investigated the effect of target ligand density, the treatment window after injury, specificity of TRAP binding peptide (TBP), the extent of TRAP deposition, and underlying genetic factors (e.g., mouse strain differences) on TBP-NP targeting. Data based on in vitro binding studies and in vivo biodistribution analyses using a murine femoral fracture model suggest that TBP-NP-TRAP interactions and TBP-NP bone accumulation were ligand-density-dependent; in vitro, TRAP affinity was correlated with ligand density up to the maximum of 200,000 TBP ligands/NP, while NPs with 80,000 TBP ligands showed 2-fold increase in fracture accumulation at day 21 post injury compared with that of untargeted or scrambled controls. While fracture accumulation exhibited similar trends when injected at day 3 compared to that at day 21 postfracture, there were no significant differences observed between TBP-functionalized and control NPs, possibly due to saturation of TRAP by NPs at day 3. Leveraging a calcium-depletion diet, TRAP deposition and TBP-NP bone accumulation were positively correlated, confirming that TRAP-TBP binding leads to TBP-NP bone accumulation in vivo. Furthermore, TBP-NP exhibited similar bone accumulation in both C57BL/6 and BALB/c mouse strains versus control NPs, suggesting the broad applicability of TBP-NP regardless of the underlying genetic differences. These studies provide insight into TBP-NP design, mechanism, and therapeutic windows, which inform NP design and treatment strategies for fractures and other bone-associated diseases that leverage TRAP, such as marrow-related hematologic diseases.

Photo-responsive doxorubicin delivery: Nanogel systems based on azobenzene and host-guest interactions enhanced by squeezing action

Conventional chemotherapy methods impact both normal and cancerous cells; therefore, it is essential to design drug delivery systems to reduce undesired drug effects. Nano-scaled drug delivery systems have the advantage of high retention time in blood as well as the capability of conventional penetration into tissue barriers. In this study, light-sensitive biocompatible nanogels with a core-shell structure have been synthesized and characterized as drug delivery system loaded with doxorubicin (DOX). These smart nanogels possess a hydrophobic core, coated with hydrophilic starch polymeric chains, which are modified with β-cyclodextrin (βCD). The core-shell formation is based on host-guest interaction between azobenzene rings as photochromic agents and βCD hydrophobic cavities. The mechanism of drug release is based on the cis-trans isomerization of azobenzene molecules upon light irradiation and dissociation of crore-shell entities. Due to this isomerization, shrinkage of hydrophobic core and removal of shell occurred simultaneously, which assist the drug release. In conclusion, a nanoscale carrier was designed with sustainable drug release under light irradiation as an external and non-contact stimulus. The synthesized nanogels were characterized by FT-IR, 1H NMR, SEM, DLS, and TEM. In addition, the MTT assay proposed that the viability of the A-431 cells has plunged in the presence irradiated nanogels, also histological studies were performed to evaluate the efficacy of the prepared nanogels in cancerous tissues.

The Lawson-loaded β-cyclodextrin nanocarriers (LB-NCs) a novel targeted cancer cell in stomach and breast cancer as a drug delivery system.

Applying nanotechnology to design drug delivery systems is a promising turning point in cancer treatment strategies. In the current study, Lawson, a nonpolar anticancer phytochemical, was entrapped into β-cyclodextrin polymer to evaluate its selective cytotoxicity in several types of human cancer cell lines including MCF-7, AGS, A549, and PC3. The Lawson-loaded β-cyclodextrin nanocarriers (LB-NCs) were produced by applying a high-energy ultrasound-mediated homogenization technique. The LB-NCs were characterized by applying dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential, and field emission scanning electron microscopy (FESEM) analysis. Also, the selective cytotoxic impact of the LB-NCs was studied by conducting the MTT assay on human MCF-7, AGS, A549, and PC3 cancer cell lines. Finally, the type of cellular death was evaluated by measuring the cell cycle status and apoptotic gene expression profile of the treated MCF-7 cells by conducting flow cytometry and Q-PCR methods, respectively. The synthesized negatively charged (- 23.8 mV) nanoparticles (348.12 nm) exhibited apoptotic activity in the human breast MCF-7 cancer cells by upregulating the apoptotic gene expression profile (Caspase 3, 8, and 9). The LB-NCs exhibited a significant selective cytotoxic effect on the human cancer cell lines compared with the normal HUVEC cells. However, variable toxic intensities were detected depending on the cancer cell type. Selective cancer cell-depended anticancer activity of the produced LB-NCs has the potential to be considered their safe efficient targeted anticancer activity. However, studying the animal cancer models has to be conducted to verify their selective toxicity and clarify the cellular death mechanism.

Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bonds results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within PNS-SS-DOX is responsive to the intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

Salvia miltiorrhiza Bunge (Danshen) based nano-delivery systems for anticancer therapeutics

BackgroundThe ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PurposeWith the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. MethodsA systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. ResultsThe main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. ConclusionThis review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.

Design and Evaluation of Osmotic Drug Delivery System of Efonidipine

A diabetic foot ulcer (DFU) is the prime cause of poor quality of life among diabetic patients. DFU leads to physical disability and an enormous economic burden on diabetic patients. The development and prognosis of DFU are preventable in most patients by modifying the risk factors for DFU. Programs intervened by clinical pharmacists can enhance rational drugs use and improve the early identification and prevention of DFU. This study intended to prove the beneficial outcome in identifying the risk factors and the provision of patient-tailored referral advice regarding DFU among diabetic patients. This cross-sectional study assessed the neuropathy through Michigan Neuropathy Screening Instrument (MNSI), Monofilament and Vibration test using Tuning Fork and Handheld Doppler for assessing the lower limb vascular disease as per NICE guideline among 137 diabetic patients. 64% of patients were found to have symptoms of neuropathy through the neuropathy assessment test whereas 36% did not have the symptoms. Foot sensory using monofilament test was found to be normal in 49.64% of DFU patients, reduced in 43.80%, and absent in 6.57% of DFU patients. The Ankle Brachial Index (ABI) was found to be normal in 48% of patients, mild in 34% of patients, moderate in 12% of patients, and incompressible in 6% of patients. Clinical Pharmacist intervened risk assessment through Hand-held Doppler, MNSI instrument, and Vibration test helped in screening the DFU patients for Neuropathy, and implementation of effective per patient-tailored education was found to be beneficial in the early identification of DFU and referral to specialty hospitals

Bio‐based pH‐responsive nanofibrous membranes for controlled release of tetracycline hydrochloride

AbstractDesign and fabrication of pH‐responsive nanofibrous membranes by biomaterials is a key step for drug delivery systems. Currently, there is an increasing attention on design of biocompatible nanofibrous drug delivery systems. Here, a bio‐based pH‐responsive nanofibrous membranes loaded with antibiotic were fabricated for the controlled release of tetracycline hydrochloride (TH). The in vitro drug release behavior of varied pH‐responsive nanofibrous with different mass ratios of poly (lactic acid) (PLA) and cellulose acetate phthalate (CAP) was investigated to clarify the release mechanism. TH initial burst release within 20 mins was large than 97.5% for PLA/CAP/TH NFM under alkaline conditions (pH = 8). The antioxidant activity of TH loaded PLA/CAP NFMs are all higher than 55% after 30 mins. The prepared fibrous membranes possess sufficient antibacterial activity against both to Gram‐negative and Gram‐positive bacteria. At the same time, it also has good biocompatibility. Therefore, the fabricated nanofibrous membranes was demonstrated to be a pH‐responsive nanoplatform for drug delivery.

The Design and Optimization of Fast-dissolving Oral Drug Delivery System (ODDS) of Valproic Acid (VLA) an Anti-epileptic Category Drug

Objective: Develop and optimize a fast-dissolving oral drug delivery system (ODDS) for Valproic acid (VLA), an anti-epileptic drug, using Design of Experiments (DoE). Methodology: DoE, a powerful tool for optimizing formulations, was employed to investigate the impact of various factors on the dissolution rate of VLA ODDS. Key factors studied included superdisintegrants (sodium starch glycolate, crospovidone), diluents (lactose, microcrystalline cellulose), and lubricants (magnesium stearate). A Box-Behnken design was used to create experimental runs, and the dissolution rate at 30 minutes was chosen as the response variable. Results: The DoE analysis revealed significant interactions between factors affecting the dissolution rate. The formulation containing sodium starch glycolate, lactose, and low magnesium stearate concentration exhibited the fastest dissolution rate (Q30 > 85% in 10 minutes). Conclusion: This study successfully designed and optimized a fast-dissolving ODDS for VLA using DoE. The optimized formulation offered rapid drug release, potentially improving patient compliance and therapeutic efficacy. This approach demonstrates the effectiveness of DoE in optimizing pharmaceutical formulations for enhanced performance. The findings indicated that the RSM was effectively utilized in developing valproic acid fast dispersible tablets, thus representing a significant progress in the treatment of epileptic seizures.

Controlled Sublimation Rate of Guest Drug from Polymorphic Forms of a Cyclodextrin-Based Polypseudorotaxane Complex and Its Correlation with Molecular Dynamics as Probed by Solid-State NMR.

Encapsulation of active pharmaceutical ingredients (APIs) in confined spaces has been extensively explored as it dramatically alters the molecular dynamics and physical properties of the API. Herein, we explored the effect of encapsulation on the molecular dynamics and physical stability of a guest drug, salicylic acid (SA), confined in the intermolecular spaces of γ-cyclodextrin (γ-CD) and poly(ethylene glycol) (PEG)-based polypseudorotaxane (PPRX) structure. The sublimation tendency of SA encapsulated in three polymorphic forms of the γ-CD/PEG-based PPRX complex, monoclinic columnar (MC), hexagonal columnar (HC), and tetragonal columnar (TC), was investigated. The SA sublimation rate was decreased by 3.0-6.6-fold and varied in the order of MC form > HC form > TC form complex. The 13C and 1H magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectra and 13C spin-lattice relaxation time (T1) indicated that the encapsulated SA molecules existed as the monomeric form, and its molecular mobility increased in the order of MC form > HC form > TC form complex. In the complexes, a rapid chemical exchange between two dynamic states of SA (free and bound) was suggested, with varying adsorption/desorption rates accounting for its distinct molecular mobility. This adsorption/desorption process was influenced by proton exchange at the interaction site and interaction strength of SA in the complexes, as evidenced by 1H MAS spectra and temperature dependency of the 13C carbonyl chemical shift. A positive correlation between the molecular mobility of SA and its sublimation rate was established. Moreover, the molecular mobility of γ-CD and PEG in the complexes coincided with that of SA, which can be explained by fast guest-driven dynamics. This is the first report on the stability improvement of an API through complexation in polymorphic supramolecular host structures. The relationship between the molecular dynamics and physical properties of encapsulated API will aid in the rational design of drug delivery systems.

Design, Evaluation and Optimization of Albuterol Sulphate and Theophylline Pulsincap drug delivery system for chronotherapy of Asthma

The aim of the current study was to design and develop and evaluate pulsatile drug delivery system of Albuterol Sulphate and Theophylline for the treatment of Asthma. The capsule body was made water insoluble by cross linked with formaldehyde vaopur. The treatment of Formalin was adopted to modify the gelatin capsule solubility. The formalin residue was carried out by quantitative test. The drug-excipient compatibility is done by FTIR and UV . The pulsincap formulation were prepared by using hydrogel plug of various components. The drug content of the formulation of pulsincap was found to be in the general range. The invitro drug release studies in ph1.2 .6.2 and 7.4 buffern was noticed to be zero percent and capsule was stable for 2 hours drug the studyF5 formulation batch was selected which was best and good formulation and promoted maximum drug release of  96.29%   percentage at  phosphate buffers when compared with other formulation. Pulsincap formulation can be adopted for optimum delivery of pellets in the treatment as per chronotherapy
 Keywords:  Theophylline, quantitative test, invitro drug release studies, phosphate buffers6.2 and 7.4.

Nanoparticle-Based Drug Delivery Systems for Enhancing Bone Regeneration.

The treatment of bone defects has been a long-standing challenge in clinical practice. Among the various bone tissue engineering approaches, there has been substantial progress in the development of drug delivery systems based on functional drugs and appropriate carrier materials owing to technological advances in recent years. A large number of materials based on functional nanocarriers have been developed and applied to improve the complex osteogenic microenvironment, including for promoting osteogenic activity, inhibiting osteoclast activity, and exerting certain antibacterial effects. This Review discusses the physicochemical properties, drug loading mechanisms, advantages and disadvantages of nanoparticles (NPs) used for constructing drug delivery systems. In addition, we provide an overview of the osteogenic microenvironment regulation mechanism of drug delivery systems based on nanoparticle (NP) carriers and the construction strategies of drug delivery systems. Finally, the advantages and disadvantages of NP carriers are summarized along with their prospects and future research trends in bone tissue engineering. This Review thus provides advanced strategies for the design and application of drug delivery systems based on NPs in the treatment of bone defects.

Design, optimization, and characterization of covalent organic framework-based nanoparticle drug delivery systems

Drug delivery system has became a research hotspot due to its excellent targeting ability and drug-controlled releases. Herein, a hierarchically flower-like hollow COF (HFH-COF) is synthesized via a simple one-step reaction method at room temperature. The as-prepared HFH-COF has high specific surface area, uniform pore size and pH sensitivity. Based on drug loading experiments using Adriamycin (DOX) as a model molecule, HFH-COF exhibits high drug loading capabilities. The drug release curves under different pH conditions show that HFH-COF is pH sensitive. In vitro cell experiments further confirmed that HFH-COF has good biocompatibility. DOX can be effectively released from HFH-COF to kill tumor cells. The as-prepared HFH-COF drug-loading system has exceptional drug loading ability, excellent biocompatibility, pH sensitivity of the tumor microenvironment, as well as good the potential application prospects in tumor treatment. Overall, a new COF-based drug delivery systems have been developed, and COFs are expanding the field of drug carriers as well.

An Albumin-Holliday Junction Biomolecular Modular Design for Programmable Multifunctionality and Prolonged Circulation.

Combinatorial properties such as long-circulation and site- and cell-specific engagement need to be built into the design of advanced drug delivery systems to maximize drug payload efficacy. This work introduces a four-stranded oligonucleotide Holliday Junction (HJ) motif bearing functional moieties covalently conjugated to recombinant human albumin (rHA) to give a "plug-and-play" rHA-HJ multifunctional biomolecular assembly with extended circulation. Electrophoretic gel-shift assays show successful functionalization and purity of the individual high-performance liquid chromatography-purified modules as well as efficient assembly of the rHA-HJ construct. Inclusion of an epidermal growth factor receptor (EGFR)-targeting nanobody module facilitates specific binding to EGFR-expressing cells resulting in approximately 150-fold increased fluorescence intensity determined by flow cytometric analysis compared to assemblies absent of nanobody inclusion. A cellular recycling assay demonstrated retained albumin-neonatal Fc receptor (FcRn) binding affinity and accompanying FcRn-driven cellular recycling. This translated to a 4-fold circulatory half-life extension (2.2 and 0.55 h, for the rHA-HJ and HJ, respectively) in a double transgenic humanized FcRn/albumin mouse. This work introduces a novel biomolecular albumin-nucleic acid construct with extended circulatory half-life and programmable multifunctionality due to its modular design.

Quillaja and Sapindus saponins influence on effect on solubilization of Polymyxin B peptide antibiotic in aqueous solutions

Knowing and understanding the interactions between surfactants and pharmaceuticals is crucial for the proper and efficient design of drug delivery systems. The goal of such systems is to ensure that the drug is as bioavailable to cells as possible. The subject of this study was the effect of natural surfactants, saponins from Quillaja saponaria Mol. and Sapindus mukorossi L., on the behavior of the antibiotic Polymyxin B in aqueous solutions at 30 °C and atmospheric pressure. The conducted research showed that the tested surfactants in the concentration range up to 5 mg mL−1 did not affect the solubility of the antibiotic, but increased the value of the octanol–water partition coefficient (Kow). At concentrations of plant saponins from both sources, Kow slightly increased from 0.19 (control sample) to 0.40 (at 5 mg mL−1). The presence of surfactants also led to changes in the particle size distribution of Polymyxin B solutions and also in their zeta potential values. There was also a clear effect of saponins on the freezing point of the Polymyxin solution, but no significant changes in the melting point were observed. The collected results provide new knowledge about the interactions of plant surfactants and peptides based on the example of Polymyxin B, which opens wider possibilities for their use in drug delivery systems.