Drug-loaded Particles Research Articles

Synthesis and Characterization of N-Doped Carbon Quantum Dots and its Application for Efficient Delivery of Curcumin in Live Cell.

To improve bioavailability, enhance the solubility and stability of the hydrophobic drug curcumin, nanoparticles such as carbon quantum dots (CQDs) are unique choices. In this study, we present a simple, cost-effective, and eco-friendly method for synthesizing nitrogen-doped carbon quantum dots (N-CQDs) and their application in the efficient delivery of hydrophobic drugs curcumin into live cancer cells. The N-CQDs produced in this study exhibit excellent water solubility, remarkable stability, and high biocompatibility. To synthesize the N-CQD, we use a carbon source found naturally (lemon juice) and for doping, we use N-rich doping agents such as ethylene diamine and urea by using eco-friendly chemical oxidation methods. The resulting N-CQDs, with particle sizes under 10 nm, exhibit a good quantum yield, reinforcing their utility for biomedical applications. N-CQDs and drug-loaded particles are evaluated using various techniques like UV-Vis, Fluorescence Spectroscopy, Dynamic Light Scattering (DLS), and Atomic Force Microscopy (AFM) as well. Additionally, we report a remarkable method to use N-CQDs as carriers for the anticancer drug curcumin, significantly enhancing the solubility in live cells. Our research also delved into the application of N-CQDs in in vivo bioimaging and drug release studies within live cancer cells, with a particular focus on their pH-dependence behavior.

Elongated Particles Show a Preferential Uptake in Invasive Cancer Cells.

Mechanically driven cellular preference for drug carriers can enhance selectivity in cancer therapy, underscoring the importance of understanding the physical aspects of particle uptake. In this study, it was hypothesized that elongated particles might be preferentially taken up by deformable, aggressive cancer cells compared to normal cells. Two film-stretching methods were tested for 0.8-2.4 μm polystyrene (PS) particles: one based on solubility in organic solvents and the other on heat-induced softening. The heat-induced method produced more homogenous particle batches, with a standard deviation in the particle aspect ratio of 0.42 compared to 0.91 in the solvent-based method. The ability of cells to engulf elongated PS particles versus spherical particles was assessed in two subsets of human melanoma A375 cells. In the more aggressive cancer cell subset (A375+), uptake of elongated PS particles increased by 10% compared to spherical particles. In contrast, the less aggressive subset (A375-) showed a 25% decrease in uptake of elongated particles. This resulted in an uptake ratio between A375+ and A375- that was 1.5 times higher for elongated PS particles than for spherical ones. To further demonstrate relevance to drug delivery, elongated paclitaxel-loaded biodegradable, slow-releasing poly(lactic-co-glycolic) acid (PLGA) particles were synthesized. No significant difference in cytotoxic effect was observed between A375+ and A375- cells treated with spherical drug-loaded particles. However, treatment with ellipsoidal particles led to a significantly enhanced cytotoxic effect in aggressive cells compared to less aggressive cells. These findings present promising directions for tailored cancer drug delivery and demonstrate the importance of particle physical properties in cellular uptake and drug delivery mechanisms.

Physico-Chemical Characterizations of Composited Calcium-Ortho-Phosphate Porous Particles and Their Controlled Release Behavior of Clindamycin Phosphate and Amikacin Sulfate.

The porous particles prepared from composited calcium-ortho-phosphate (biphasic), Thai silk fibroin, gelatin, and alginate, with an organic to inorganic component ratio of 15.5:84.5, were tested for their abilities to control the release of the commercialized antibiotic solutions, clindamycin phosphate (CDP) and amikacin sulfate (AMK). The in vitro biodegradability tests complying to the ISO 10993-13:2010 standard showed that the particles degraded <20 wt% within 56 days. The drugs were loaded through a simple adsorption, with the maximum loading of injection-graded drug solution of 43.41 wt% for CDP, and 39.08 wt% for AMK. The release profiles from dissolution tests of the drug-loaded particles varied based on the adsorption methods used. The drug-loaded particles (without a drying step) released the drug immediately, while the drying process after the drug loading resulted in the sustained-release capability of the particles. The model-fitting of drug release profiles showed the release driven by diffusion with the first-ordered kinetic after the initial burst release. The released CDF and AMK from particles could sustain the inhibition of Gram-positive bacteria and Gram-negative bacteria, respectively, for at least 72 h. These results indicated the potential of these composited particles as controlled-release carriers for CDP and AMK.

Injectability of high concentrated suspensions using model microparticles

Administration of high-concentrated suspension formulations (i.e., solid particles dispersed in a liquid vehicle) can be limited due to their greater propensity for needle occlusion. The physical interaction between the solid phase (i.e., particles), the vehicle (i.e., flow field), and injection devices could result in the formation of particle bridging or filtering, posing a major risk in dose delivery accuracy and injectability. Here, given the limited understanding on how clogging initiates in syringe and needle delivery systems, we report an experimental approach to fully characterize the transient injection behavior of suspensions. In particular, we first established a custom fluorescence tagging and imaging technique with integrated force sensor to enable visual observation of local particle concentrations and plunger force monitoring throughout injection. Then, we investigated the effects of key formulation properties and device parameters including particle concentration and morphology, carrier viscosity, injection rate, needle and syringe sizes, and tissue backpressure on the incidence of suspension particle jamming and needle clogging. We performed systematic benchmark studies demonstrating that increasing needle inner diameter (ID) and particle density considerably reduced clogging risk, while increasing vehicle viscosity, particle size, and tissue backpressure significantly increased clogging. The experimental framework presented is amenable to quantifying clogging risk in drug-loaded particle suspensions and provides a guideline to make informed decisions on the tradeoffs between creating particles for pharmaceutical impact and feasibility of injection delivery.

Paravertebrally-Injected Multifunctional Hydrogel for Sustained Anti-Inflammation and Pain Relief in Lumbar Disc Herniation.

Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.

PEGylated Micro/Nanoparticles Based on Biodegradable Poly(Ester Amides): Preparation and Study of the Core-Shell Structure by Synchrotron Radiation-Based FTIR Microspectroscopy and Electron Microscopy.

Surface modification of drug-loaded particles with polyethylene glycol (PEG) chains is a powerful tool that promotes better transport of therapeutic agents, provides stability, and avoids their detection by the immune system. In this study, we used a new approach to synthesize a biodegradable poly(ester amide) (PEA) and PEGylating surfactant. These were employed to fabricate micro/nanoparticles with a core-shell structure. Nanoparticle (NP)-protein interactions and self-assembling were subsequently studied by synchrotron radiation-based FTIR microspectroscopy (SR-FTIRM) and transmission electron microscopy (TEM) techniques. The core-shell structure was identified using IR absorption bands of characteristic chemical groups. Specifically, the stretching absorption band of the secondary amino group (3300 cm-1) allowed us to identify the poly(ester amide) core, while the band at 1105 cm-1 (C-O-C vibration) was useful to demonstrate the shell structure based on PEG chains. By integration of absorption bands, a 2D intensity map of the particle was built to show a core-shell structure, which was further supported by TEM images.

Mix and Shake: A Mild Way to Drug-Loaded Lysozyme Nanoparticles.

Biocompatible nanoparticles as drug carriers can improve the therapeutic efficiency of hydrophobic drugs. However, the synthesis of biocompatible and biodegradable polymeric nanoparticles can be time-consuming and often involves toxic solvents. Here, a simple method for protein-based stable drug-loaded particles with a narrow polydispersity is introduced. In this process, lysozyme is mixed with hydrophobic drugs (curcumin, ellipticine, and dasatinib) and fructose to prepare lysozyme-based drug particles of around 150 nm in size. Fructose is mixed with the drug to generate nanoparticles that serve as templates for the lysozyme coating. The effect of lysozyme on the physicochemical properties of these nanoparticles is studied by transmission electron microscopy (TEM) and scattering techniques (e.g., dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS)). We observed that lysozyme significantly stabilized the curcumin fructose particles for 7 days. Moreover, additional drugs, such as ellipticine and dasatinib, can be loaded to form dual-drug particles with narrow polydispersity and spherical morphology. The results also reveal that lysozyme dual ellipticine/dasatinib curcumin particles enhance the cytotoxicity and uptake on MCF-7 cells, RAW 264.7 cells, and U-87 MG cells due to the larger and rigid hydrophobic core. In summary, lysozyme in combination with fructose and curcumin can serve as a powerful combination to form protein-based stable particles for the delivery of hydrophobic drugs.

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.

Preparation of Hirudin-Loaded Chitosan/Polycaprolactone Bowl-Shaped Particles and an Application for a Drug Delivery System

Atherosclerosis, a disease that mainly affects human blood vessels, can cause various cerebral ischaemic diseases such as coronary heart disease and peripheral arterial disease. However, conventional drugs for the treatment of atherosclerosis have the disadvantages of low bioavailability and high toxicity. Bowl-shaped particles not only have the excellent properties of traditional spherical particles, such as improved drug distribution, increased drug absorption, reduced drug toxicity and side effects, but also are easier to circulate in the blood for a long time, have reduced immune rejection and have a larger specific surface area. Chitosan/polycaprolactone bowl-shaped particles were prepared via electrostatic spraying, and the effects of precursor solution concentration and polymer ratio on particle morphology were investigated. Chitosan/polycaprolactone composite bowl-shaped particles containing hirudin were prepared under optimal parameters for sustained anticoagulation. The anticoagulant molecules of hirudin could be continuously released from the composite scaffold as the bowl particles degraded. The biocompatibility and haemocompatibility of the composite particles were assessed using mouse glial cells and rabbit blood, and the results showed that the cell viability of the drug-loaded particles was overall above 90% and the haemolysis rate was below 2%. By controlling the release rate of hirudin, bowl-shaped particles can achieve a long-term anticoagulant drug delivery system and have wider application potential as a novel blood contact material.

Inhibition of growth of hepatocellular carcinoma by co-delivery of anti-PD-1 antibody and sorafenib using biomimetic nano-platelets

BackgroundTraditional nanodrug delivery systems have some limitations, such as eliciting immune responses and inaccuracy in targeting tumor microenvironments.Materials and methodsTargeted drugs (Sorafenib, Sora) nanometers (hollow mesoporous silicon, HMSN) were designed, and then coated with platelet membranes to form aPD-1-PLTM-HMSNs@Sora to enhance the precision of drug delivery systems to the tumor microenvironment, so that more effective immunotherapy was achieved.ResultsThese biomimetic nanoparticles were validated to have the same abilities as platelet membranes (PLTM), including evading the immune system. The successful coating of HMSNs@Sora with PLTM was corroborated by transmission electron microscopy (TEM), western blot and confocal laser microscopy. The affinity of aPD-1-PLTM-HMSNs@Sora to tumor cells was stronger than that of HMSNs@Sora. After drug-loaded particles were intravenously injected into hepatocellular carcinoma model mice, they were demonstrated to not only directly activate toxic T cells, but also increase the triggering release of Sora. The combination of targeted therapy and immunotherapy was found to be of gratifying antineoplastic function on inhibiting primary tumor growth.ConclusionsThe aPD-1-PLTM-HMSNs@Sora nanocarriers that co-delivery of aPD-1 and Sorafenib integrates unique biomimetic properties and excellent targeting performance, and provides a neoteric idea for drug delivery of personalized therapy for primary hepatocellular carcinoma (HCC).

A Detailed Review on Porous Microspheres: Methods of Preparation, Characterization, and its Applications

Porous microspheres are a new kind of carrier with high porosity, uniform porous structure, and pore size with narrow distribution. They are having inter-connective pores present externally and internally which leads to very low mass density and greater specific surface area, making them have excellent adsorption properties. Because of this uniqueness over non-porous microspheres, they are having extensive pharmaceutical applications. Porous microspheres are formulated by several methods, which involve the use of porogens or templating agents for the formation of pores, self-forming pores by particle matrices without any pore-forming agents, and chemical synthesis. These microspheres are very promising in varied fields of medicine such as enhancing of dissolution of poorly soluble drugs, developing novel drug delivery systems, and improving the functional properties of drug-loaded particles. The main factor governing their applications depends on the pore structure and porosity. Therefore, this review aims at emphasizing the principles underlying the development and evaluation of porous microspheres as a controlled and targeted drug delivery system and becomes an informative reference that can be beneficial for several interested research scholars.

Simulation of Remote Forces Generated by High-Temperature Superconducting Bulks for Magnetic Drug Delivery

The strong background fields and field gradients required for the magnetic delivery of chemotherapeutic drugs in cancer treatments has proven to be challenging to achieve at the scale of the human body. Although several magnetic drug delivery (MDD) methods have been proposed to generate adequate forces in deep tissues, current technologies lack in either force strength, directional changes and/or duty cycle of the treatment. The current MDD system capable of generating the strongest forces, dipole field navigation, uses ferromagnetic (FM) cores in the strong uniform field of an MRI to steer the drug-loaded particles. Hence, considering the nearly ten-fold increase in magnetization of high-temperature superconducting (HTS) bulks in comparison to the strongest FM, the forces obtained in dipole field navigation could potentially be increased by replacing the FM cores with HTS bulks. In this work, we evaluate two different methods for generating magnetic forces using an HTS bulk in a magnetic resonance imaging (MRI) scanner by using finite element method simulations. First, the HTS pellet is zero field cooled and inserted in the uniform field of an MRI, such that the pellet is magnetized by the fringe field of the MRI. Secondly, a field cooled HTS pellet is rotated in the uniform field of an MRI in order to generate magnetic field gradients. The magnetic forces produced by both methods are compared with those obtained by dipole field navigation. In both methods evaluated, we found that the forces generated by the HTS pellet is either complementary to or stronger than those obtained with FM cores. Therefore, this work shows that HTS bulks could potentially be used to navigate magnetic particles in the deep tissues of the human vascular network more efficiently.

CXCR4 Targeting Nanoplatform for Transcriptional Activation of Latent HIV-1 Infected T Cells.

Antiretroviral drugs are limited in their ability to target latent retroviral reservoirs in CD4+ T cells, highlighting the need for a T cell-targeted drug delivery system that activates the transcription of inactivated viral DNA in infected cells. Histone deacetylase inhibitors (HDACi) disrupt chromatin-mediated silencing of the viral genome and are explored in HIV latency reversal. But single drug formulations of HDACi are insufficient to elicit therapeutic efficacy, warranting combination therapy. Furthermore, protein kinase C activators (PKC) have shown latency reversal activity in HIV by activating the NF-κB signaling pathway. Combining HDACi (SAHA) with PKC (PMA) activators enhances HIV reservoir activation by promoting chromatin decondensation and subsequent transcriptional activation. In this study, we developed a mixed nanomicelle (PD-CR4) drug delivery system for simultaneous targeting of HIV-infected CD4+ T cells with two drugs, suberoylanilide hydroxamic acid (SAHA) and phorbol 12-myristate 13-acetate (PMA). SAHA is a HDACi that promotes chromatin decondensation, while PMA is a PKC agonist that enhances transcriptional activation. The physicochemical properties of the formulated PD-CR4 nanoparticles were characterized by NMR, CMC, DLS, and TEM analyses. Further, we investigated in vitro safety profiles, targeting efficacy, and transcriptional activation of inactivated HIV reservoir cells. Our results suggest that we successfully prepared a targeted PD system with dual drug loading. We have compared latency reversal efficacy of a single drug nanoformulation and combination drug nanoformulation. Final PD-SP-CR4 successfully activated infected CD4+ T cell reservoirs and showed enhanced antigen release from HIV reservoir T cells, compared with the single drug treatment group as expected. To summarize, our data shows PD-SP-CR4 has potential T cell targeting efficiency and efficiently activated dormant CD4+ T cells. Our data indicate that a dual drug-loaded particle has better therapeutic efficacy than a single loaded particle as expected. Hence, PD-CR4 can be further explored for HIV therapeutic drug delivery studies.

Polymeric Microspheres Designed to Carry Crystalline Drugs at Their Surface or Inside Cavities and Dimples.

Injectable polymer microparticles with the ability to carry and release pharmacologically active agents are attracting more and more interest. This study is focused on the chemical synthesis, characterization, and preliminary exploration of the utility of a new type of injectable drug-releasing polymer microparticle. The particles feature a new combination of structural and physico-chemical properties: (i) their geometry deviates from the spherical in the sense that the particles have a cavity; (ii) the particles are porous and can therefore be loaded with crystalline drug formulations; drug crystals can reside at both the particle's surfaces and inside cavities; (iii) the particles are relatively dense since the polymer network contains covalently bound iodine (approximately 10% by mass); this renders the drug-loaded particles traceable (localizable) by X-ray fluoroscopy. This study presents several examples. First, the particles were loaded with crystalline voriconazole, which is a potent antifungal drug used in ophthalmology to treat fungal keratitis (infection/inflammation of the cornea caused by penetrating fungus). Drug loading as high as 10% by mass (=mass of immobilized drug/(mass of the microparticle + mass of immobilized drug) × 100%) could be achieved. Slow local release of voriconazole from these particles was observed in vitro. These findings hold promise regarding new approaches to treat fungal keratitis. Moreover, this study can help to expand the scope of the transarterial chemoembolization (TACE) technique since it enables the use of higher drug loadings (thus enabling higher local drug concentration or extended therapy duration), as well as application of hydrophobic drugs that cannot be used in combination with existing TACE embolic particles.

The interplay of solvent-drug-protein interactions during albumin nanoparticles formulations for temozolomide delivery to brain cancer cells.

Temozolomide (TMZ), the first line for glioma therapy, suffers from stability at physiological pH. TMZ was selected as a challenging model drug for loading into human serum albumin nanoparticles (HSA NPs). Our aim is to optimise the conditions for TMZ loading into HSA NPs while ensuring TMZ stability. Blank and TMZ-HSA NPs were fabricated using the de-solvation technique and the effect of different formulation parameters was evaluated. For blank NPs, crosslinking time had no significant effect on NPs' size while acetone produced significantly smaller particles than ethanol. Upon drug loading, though TMZ was stable in acetone and ethanol as single agents yet, ethanol-based NPs showed misleadingly high EE% due to drug instability in ethanol formulations as evident by the UV spectrum.The optimum conditions for drug-loaded particles were: 10 mg/ml HSA, 4 mg TMZ using acetone, yielded NPs with 145 nm in diameter, ξ of -16.98 mV and 0.16% DL. The selected formula reduced the cell viabilities of GL261 glioblastoma cells and BL6 glioblastoma stem cells to 61.9% and 38.3%, respectively. Our results corroborated that careful manipulation of TMZ formulation processing parameters is crucial for encapsulating such chemically unstable dug while simultaneously ensuring its chemical stability.

Rapid Indomethacin Release from Porous Pectin Particles as a Colon-Targeted Drug Delivery System.

The conventional pectin delivery systems in the colon are often impaired by a slow release rate. Nanostructured particles, especially porous ones, have gained popularity as drug delivery systems owing to their high mass transfer efficiency. In this research, porous pectin particles were synthesized as drug carriers (using indomethacin as a model drug) via template-assisted spray drying. Specific surface areas of the porous pectin particles have been improved by up to 203 m2 g-1 compared with nonporous particles (1 m2 g-1). The porous structure shortened the diffusion path and improved the release rate of drug molecules. Additionally, the predominant drug release mechanism from porous pectin particles is Fickian diffusion, which is different from the combination of erosion and diffusion mechanism observed for nonporous particles. As a result, these porous drug-loaded pectin particles demonstrated rapid drug release rates of up to three times faster than nonporous particles. Control of the release rate could be achieved by changing the porous structure of the particles. This strategy is an efficient means to synthesize porous particles allowing rapid drug release into the colonic target.

Hollow Particles Obtained by Prilling and Supercritical Drying as a Potential Conformable Dressing for Chronic Wounds.

The production of aerogels for different applications has been widely known, but the use of polysaccharide-based aerogels for pharmaceutical applications, specifically as drug carriers for wound healing, is being recently explored. The main focus of this work is the production and characterization of drug-loaded aerogel capsules through prilling in tandem with supercritical extraction. In particular, drug-loaded particles were produced by a recently developed inverse gelation method through prilling in a coaxial configuration. Particles were loaded with ketoprofen lysinate, which was used as a model drug. The core-shell particles manufactured by prilling were subjected to a supercritical drying process with CO2 that led to capsules formed by a wide hollow cavity and a tunable thin aerogel layer (40 μm) made of alginate, which presented good textural properties in terms of porosity (89.9% and 95.3%) and a surface area up to 417.0 m2/g. Such properties allowed the hollow aerogel particles to absorb a high amount of wound fluid moving very quickly (less than 30 s) into a conformable hydrogel in the wound cavity, prolonging drug release (till 72 h) due to the in situ formed hydrogel that acted as a barrier to drug diffusion.

FOLFIRINOX-loaded immunoliposome-like particles for localized pancreatic cancer treatment

FOLFIRINOX therapy, a combination of oxaliplatin, 5-fluorouracil, irinotecan, and leucovorin, is one of the most applied treatment schemes for pancreatic adenocarcinoma. However, because this form of treatment causes significant side effects, it has become important to reduce the dose of the drug administered to the patients and target the drug to the tumor tissue. This study presents the liposomal type of this therapy scheme to demonstrate its applicability to localized chemotherapy strategies. Briefly, lipid-based liposome-like particles have been synthesized and physically, chemically, and thermally characterized. Following the decoration of the liposome-like particles with anti-Mucin-4, a malignancy marker for pancreatic adenocarcinoma, the encapsulation efficiency of the FOLFIRINOX components and release profile of the FOLFIRINOX-loaded liposome-like particles have been analyzed using the high-pressure liquid chromatography. Cytotoxicity analyses and cellular encapsulation studies of Mucin-4-targeted liposome-like particles were performed in HPAF-II (ascites-derived cell, Mucin-4(+)) and PANC-I (tumor-derived cell, Mucin-4(−)) cells. The results have shown that Mucin-4-targeted liposome-like particles enter HPAF-II cells more selectively than PANC-I cells. Besides, after the FOLFIRINOX application, a significant difference was observed between the viability of HPAF-II and PANC-I cells at 100-fold dilution. In genotoxicity and apoptosis analysis, it was found that drug-loaded liposome-like particles caused DNA damage in cancer cells with the increase in concentration. The study suggests that Mucin-4-targeted liposome-like particles can provide superior patient welfare and a promising treatment model for pancreatic adenocarcinoma and can be used in localized chemotherapy applications due to their long-term stability, nanoscale size, and target-driven nature.

Biodegradable Magnetic Hydrogel Robot with Multimodal Locomotion for Targeted Cargo Delivery.

Recent strides in the development of untethered miniature robots have shown the advantages of diverse actuation methods, flexible maneuverability, and precise locomotion control, which has made miniature robots attractive for biomedical applications such as drug delivery, minimally invasive surgery, and disease diagnosis. However, biocompatibility and environmental adaptability are among the challenges for further in vivo applications of miniature robots due to the sophisticated physiological environment. Herein, we propose a biodegradable magnetic hydrogel robot (BMHR) that possesses precise locomotion with four stable motion modes, namely tumbling mode, precession mode, spinning-XY mode, and spinning-Z mode. Using a homemade vision-guided magnetic driving system, the BMHR can achieve flexible conversion between the different motion modes to cope with changes in complex environments, and its superior ability to cross obstacles is demonstrated. In addition, the transformation mechanism between different motion modes is analyzed and simulated. Benefiting from the diverse motion modes, the proposed BMHR has promising applications in drug delivery, showing remarkable effectiveness in targeted cargo delivery. The BMHR's biocompatible property, multimodal locomotion, and functionality with drug-loaded particles can provide a new perspective to combine miniature robots with biomedical applications.

In Vitro Release and In Vivo Pharmacokinetics of Praziquantel Loaded in Different Polymer Particles.

Approximately 1 billion people are affected by neglected diseases around the world. Among these diseases, schistosomiasis constitutes one of the most important public health problems, being caused by Schistosoma mansoni and treated through the oral administration of praziquantel (PZQ). Despite being a common disease in children, the medication is delivered in the form of large, bitter-tasting tablets, which makes it difficult for patients to comply with the treatment. In order to mask the taste of the drug, allow more appropriate doses for children, and enhance the absorption by the body, different polymer matrices based on poly(methyl methacrylate) (PMMA) were developed and used to encapsulate PZQ. Polymer matrices included PMMA nano- and microparticles, PMMA-co-DEAEMA (2-(diethylamino)ethyl methacrylate), and PMMA-co-DMAEMA (2-(dimethylamino)ethyl methacrylate) microparticles. The performances of the drug-loaded particles were characterized in vitro through dissolution tests and in vivo through pharmacokinetic analyses in rats for the first time. The in vitro dissolution studies were carried out in accordance with the Brazilian Pharmacopeia and revealed a good PZQ release profile in an acidic medium for the PMMA-DEAEMA copolymer, reaching values close to 100 % in less than 3 h. The in vivo pharmacokinetic analyses were conducted using free PZQ as the control group that was compared with the investigated matrices. The drug was administered orally at doses of 60 mg/kg, and the PMMA-co-DEAEMA copolymer microparticles were found to be the most efficient release system among the investigated ones, reaching a Cmax value of 1007 ± 83 ng/mL, even higher than that observed for free PZQ, which displayed a Cmax value of 432 ± 98 ng/mL.