Sustained Drug Release Properties Research Articles

Influence of design parameters on sustained drug release properties of 3D-printed theophylline tablets

The application of three-dimensional printing (3DP) in the pharmaceutical industry brings a broad spectrum of benefits to patients by addressing individual needs and improve treatment success. This study investigates the sustained release properties of 3DP tablets containing Theophylline (TPH), which is commonly used to treat respiratory diseases and recently having a comeback due to its potential in the treatment of conditions like Covid-19. Since TPH is a narrow therapeutic window (NTW) drug with serious side effects in the event of overdose, the release properties must be observed particularly closely. We employed a state-of-the-art single screw extrusion 3D printer, which is fed with granules containing the drug. By employing a Taguchi orthogonal array design of experiments (DOE), tablet design parameters and factor related process stability were sought to be evaluated fundamentally. Following this, examinations regarding tailored TPH dosages were undertaken and a relationship between the real printed dose of selected tablet designs and their sustained drug release was established. The release profiles were analyzed using different mathematical model fits and compared in terms of mean dissolution times (MDT). Finally, in-vivo/in-vitro correlation (IVIVC) and physiologically based pharmacokinetic (PBPK) modeling showed that a paradigm patient group could be covered with the dosage forms produced.

Deferoxamine-Loaded Chitosan-Based Hydrogel on Bone Implants Showing Enhanced Bond Strength and Pro-Angiogenic Effects.

Angiogenesis is vital for bone fracture healing and plays a significant role in the fate of orthopedic implants. The growth and maintenance of new blood vessels at the fracture site of patients is essential, which promotes the clinical outcome of plasma sprayed Ti (PST) coated orthopedic implants. In order to endow the PST coating with pro-angiogenic effects, deferoxamine-loaded chitosan-based hydrogel was fabricated on the coating surface. Polydopamine-modified chitosan (CS/PDA) hydrogel exhibited enhanced bonding strength to PST coatings as evidenced by scratch test. The deferoxamine-loaded CS/PDA (CS/PDA-DFO) exhibited a sustained drug-release property, and the cumulative concentration of released DFO reached 20.21 μg/mL on day 7. PST-CS/PDA with higher wettability and active group quantity enhanced the viability and adhesion characteristics of human umbilical vein endothelial cells (HUVECs) and upregulated the secretion level of nitric oxide and vascular endothelial growth factor. Moreover, the introduction of DFO in PST-CS/PDA further enhanced the pro-angiogenic effects. Above all, this study offers a novel approach for developing hydrogel coating on orthopedic implants showing enhanced bonding strength and pro-angiogenic effects.

Surface Modification of Hydroxyapatite Coating for Enhanced Antibiotic Therapy

A major strategy to combat implant-associated infections is to develop implant coatings with intrinsic antibacterial activity. Since hydroxyapatite (HAp) coatings and antibiotic administration are commonly used in clinical settings, developing HAp-coated implants with localized antibiotic-releasing properties has attracted popularity. Considering the antibacterial metal species (Ag, Zn, Cu, etc.) in metal–organic frameworks and their drug delivery capacity, in this study, a gentamicin-loaded zeolitic imidazolate framework-8 nanolayer was deposited on a plasma-sprayed HAp coating (HAp/ZIF-8@Gent), which served as a Gent and Zn2+ reservoir. The investigation on the binding interaction between ZIF-8 and HAp indicated that the growth of ZIF-8 was through a Zn2+ seed layer on the HAp coating via an adsorption–replacement mechanism, instead of simple physical adsorption. The HAp/ZIF-8@Gent coating exhibited a sustained drug-release property, and the cumulative concentration of released Gent reached 239.8 ± 7.1 μg/mL on day 8. Compared to the HAp-Zn and HAp/ZIF-8 coatings, the HAp/ZIF-8@Gent coating exhibited significantly higher antibacterial activity against E. coli. This was ascribed to the combined antibacterial effects of Zn2+ and Gent. The cytocompatibility of the HAp/ZIF-8@Gent coating was confirmed via cell proliferation. Above all, the ZIF-8-modified HAp coating with localized delivery of Gent and Zn2+ possessed excellent antibacterial activity and acceptable cytocompatibility, showing potential in mitigating implant-associated infections.

Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation

Improving the pharmacokinetics of intra-articularly injected therapeutics is a major challenge in treating joint disease. Small molecules and biologics are often cleared from the joint within hours, which greatly reduces their therapeutic efficacy. Furthermore, they are often injected at high doses, which can lead to local cytotoxicity and systemic side effects. In this study, we present modular polymer-drug conjugates of zwitterionic poly(carboxybetaine acrylamide) (pCBAA) and the anti-inflammatory glucocorticoid dexamethasone (DEX) to create cartilage-targeted carriers with slow-release kinetics. pCBAA polymers showed excellent cartilage penetration (full thickness in 1 h) and retention (>50 % after 2 weeks of washing). DEX was loaded onto the pCBAA polymer by employing two different DEX-bearing comonomers to produce pCBAA-co-DEX conjugates with different release kinetics. The slow-releasing conjugate showed zero-order release kinetics in PBS over 70 days. The conjugates elicited no oxidative stress on chondrocytes compared to dose-matched free DEX and protected bovine cartilage explants from the inflammatory response after treatment with IL-1β. By combining cartilage targeting and sustained drug release properties, the pCBAA-co-DEX conjugates solve many issues of today's intra-articular therapeutics, which could ultimately enable better long-term clinical outcomes with fewer side effects.

Incorporation of nanoparticles in silk fibroin solution: Toward water‐stable silk fibroin films possessing silk I structure

AbstractWater‐stable silk fibroin (SF) films are normally prepared by transforming the secondary structure of SF, from amorphous silk I (random coils) to silk II (β‐sheet), via physical or chemical means. Although mechanically strong, these films are generally brittle. Herein, we prepared water‐stable flexible SF films possessing silk I rather than silk II structure. Films were prepared by casting SF solution possessing SF nanoparticles induced by two different methods: (1) pre‐prepared SF nanoparticles by ethanol were added into SF solution; (2) nanoparticles were induced in SF solution via autoclaving. These films were compared with each other and with water‐annealed and methonol‐annealed films for their secondary structure and physical properties. The as‐prepared films were primarily composed of silk I structure, as validated by x‐ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. However, the water‐annealed and methanol‐annealed films exhibited silk II structure. The films prepared by induction of nanoparticles were water‐stable, transparent, mechanically strong (tensile strength as high as 5.14 ± 1.43 MPa), exhibited tunable degradation and sustained drug release properties. As for mechanical properties, these films displayed 4 times and 12 times improved mechanical ductility as compared with water‐annealed and methanol‐annealed films, respectively. Moreover, these films exhibited fast enzymatic degradation as compared with their counterparts with silk II structure. These films hold great promise as a biomaterial for tissue engineering applications especially where flexibility and fast degradation of scaffold are important.

Chitosan-Caffeic Acid Antibacterial Coating for PDMS Surfaces: A Sustained Moxifloxacin Release and Prolonged Coating Adhesion

Central venous catheters (CVCs) are largely used to administer chemotherapy, hemodialysis, and other treatments. Mostly made of polydimethylsiloxane (PDMS), these medical devices present an intrinsic risk of infection due to the possible formation of biofilm, thus increasing the risk of complications. Drug-releasing polymer coatings are a well-recognized strategy for combating biofilm formation. However, adhesion of the coating to the substrate over time is a major challenge. Therefore, this work aimed to design a chitosan-based coating designed to have maximum adhesion and stability to guarantee sustained drug release and antibacterial properties for at least 14 days. A coating composed of chitosan (CS) as a drug carrier, caffeic acid (CA) and copper sulphate (Cu) as crosslinkers, and moxifloxacin (Mox) as an antibiotic, was deposited through a controlled casting process onto functionalized PDMS surface. PDMS surface modification was investigated by X-ray photoelectron spectroscopy (XPS), and Fourier-transfer infrared (FTIR). Antibiotic release over time was measured in pseudo-physiological conditions (pH 7.4 and at 37 °C). Indirect cytotoxicity assays were performed on human dermal fibroblasts (HDF). The adhesion of the as-designed coating was evaluated by a specially designed pull-off test, before and after aging for 14 days in PBS. XPS and FTIR analyses confirmed the successful PDMS surface modification. The CS-CA-Cu-Mox coating resulted in being non-cytotoxic towards HDF and exhibited sustained moxifloxacin release for up to 49 days. Furthermore, the CS-CA and CS-CA-Cu coatings presented antibacterial activity for 21 days against E. coli, and for 14 days against S. aureus. Importantly, the coating maintained stable adhesion after 14 days in pseudo-physiological conditions. This study provides new insights into the adhesion behavior of polymeric coatings for medical devices, which is rarely reported in the literature.

Functionalized Carbon Nano-Onions as a Smart Drug Delivery System for the Poorly Soluble Drug Carmustine for the Management of Glioblastoma.

The drug delivery system for transporting anticancer agents to targeted tissues in the body is a challenging issue. In search of a suitable biocompatible carrier having controlled and sustained drug release properties of poorly soluble drugs, carbon nano-onions (CNOs) were loaded with an anticancer drug, bis-chloroethyl nitrosourea (BCNU/carmustine). CNOs being autofluorescent, drug-loaded functionalized CNOs (f-CNO-BCNU) can be detected in vivo. Transmission electron microscopy (TEM) and differential light scattering (DLS) techniques were used to analyze the sizes of these f-CNOs. The molecular study revealed that the f-CNO-BCNU readily and noncovalently binds with the folate receptors present on the cancer cell surface in excess. Computer modeling and molecular dynamics simulation followed by binding free energy calculation shows f-CNOs have -29.9 kcal/mol binding free energy, and it noncovalently binds the receptor FRα using loop dynamics of three essential loops present in the protein along with polar stabilization interactions provided by Asp55 and Glu86 residues present in the active site. The f-CNO effectively decreased cancer cell viability with a low IC50 value (the concentration that led to 50% killing of the cells). The cell-based Franz diffusion assay was performed to study the drug release profile. The f-CNO-BCNUs also decreased the mitochondrial membrane potential of U87 cells, increased reactive oxygen species release, and caused a loss of mitochondrial membrane integrity. The f-CNOs also increased the percentage of apoptotic cells observed by the Annexin V assay. Based on observed results, it can be concluded that the f-CNO-BCNU efficiently targets the cancer cells, enhances the bioavailability of carmustine, and can be used as a smart chemotherapeutic agent. This strategy offers better patient compliance and greater bioavailability of the drug.

Psoralea corylifolia formula extract-loaded silk fibroin/polycaprolactone fibrous membrane for the treatment of colorectal cancer

Intestinal obstructions caused by intestinal tumors pose life-threatening risks to patients. Adjuvant treatment using intestinal stents carrying drug loaded membranes has the advantages of timely relief of intestinal obstruction, as well as effective inhibition of tumor progression. The present work is to develop an intestinal stent loaded with a combination of traditional Chinese medicines capable of good biocompatibility, degradability, sustained drug release and anti-tumor properties. The drug combination extract was obtained from Psoralea corylifolia formula (PCF) and then was loaded into silk fibroin (SF)/polycaprolactone (PCL) fibrous membranes using emulsion electrospinning technology. Results showed that the membrane prepared by emulsion electrospinning technology has apparent core-shell structure, and the mechanical property and hydrophilicity of the membrane are gradually improved with the addition of PCF. Drug sustained release results demonstrated that there were no bursting phenomena, and showed a gradual sustained release up to 400 h. The antitumor efficacy was assessed in vitro using a human colorectal cancer cell line HCT-116 and an epithelial cell line NCM-460. Results showed that this drug-loaded membrane sustained antitumor cell growth performance, indicating its great potential for clinical treatment for intestinal cancer in the near future.

Grafting of sinapic acid onto glucosamine nanoparticle as a potential therapeutic drug with enhanced anti-inflammatory activities in osteoarthritis treatment

Glucosamine (Glu) is a cartilage and joint fluid matrix precursor that modulates osteoarthritic joint changes. To improve the enzymatic stability, glucosamine was developed into nanoglucosamine by the ionic gelation method through sodium tripolyphosphate (TPP) as cross-linking agent. The optimized mass ratio of Glu:TPP was (3:1) with the particle size 163 ± 25 nm and surface charge −5 mV. Then Sinapic acid (SA) as a natural phenolic acid with strong antioxidant and antimicrobial activities has been grafted onto glucosamine nanoparticles (GluNPs) with grafting efficiency (73 ± 6 %). The covalent insertion of SA was confirmed by UV–Vis, FTIR, 1HNMR, XRD, and FESEM analyses and the other physicochemical properties were also characterized. SA-g-GluNPs showed spherical shape with a mean diameter of 255 ± 20 nm and zeta potential +16 mV. The in vitro release profile of SA-g-GluNPs exhibited the sustained and pH-dependent drug release property. SA-g-GluNPs had a more pronounced effect on reducing the elevated levels of LPS-induced oxidative stress and pro-inflammatory cytokines than free SA in the human chondrocyte C28/I2 cell line. Furthermore, the antibacterial properties against E. coli and S. aureus were also improved by SA-g-GluNPs. This study demonstrated the potential of phenolic acid grafted GluNPs in therapeutic drug applications for chondroprotection and food industries.

Liquid-like Oral Sustained-Release System Based on Acid-Sensitive in situ Hydrogel for Alleviate Gastrointestinal Side Effects of Indobufen

Commonly, most oral non-steroidal anti-inflammatory drugs (NSAIDs) have known gastric adverse reactions due to their long-term and high dose administration. In this study, a novel liquid sustained-release system based on multiple-unit in situ hydrogel beads was designed to address this issue. The system is composed of sodium alginate (SA), gellan gum (GG), zinc oxide (ZnO), and magnesium oxide (MgO). Furthermore, indobufen was loaded into the system to evaluate its gastric mucosal protection effect. This effect can be attributed to the topical antacid, pepsin inhibition, and sustained drug release properties of the system. It was proven that the stored solid gel system could undergo a “solid to liquid” transition after shaking. Once swallowed, the liquid gel could disperse well in the stomach as hydrogel beads. Then, the “liquid to solid” gelation occurred from the exterior to interior of each multiple-unit gel bead, triggered by the release of Zn2+ and Mg2+ from neutralization reactions. The formed gel demonstrated mild antacid effect that lasted for 3 hours and 66.3% pepsin inhibition in vivo. Moreover, the rats treated with the indobufen gel system showed a drug plasma concentration versus time curve with less fluctuation compared to the rats treated with the marketed preparation (YinDuo®) group. The gel system also exhibited an extended Tmax (6.50 hours) and reduced Cmax (52.87 μg/mL). Additionally, the gastric mucosal protection of the gel system was verified using three types of peptic gastric ulcer models. These findings suggested that this multiple-unit in situ gel could be a potential oral liquid sustained release delivery system for NSAIDs.

Synthesis of multifunctional superparamagnetic mesoporous ZnMnFe2O4@Fe–CaSiO3 core-shell for medical applications

Herein, we report the synthesis of a mesoporous calcium silicate superparamagnetic nanoparticle as ZnMnFe2O4@Fe–CaSiO3 core-shell. This core-shell nanocomposite reveals excellent properties such as mesoporous nanocomposite, superparamagnetic at room temperature, low toxicity, large surface area, tunable pore size, and easy surface manipulation. The core nanocomposite (ZnMnFe2O4) is synthesized by the hydrothermal method, which shows a superparamagnetic behavior with an excellent saturation magnetization of 52.09 emu/g. The core-shell structure is prepared by a micellar-assisted sol-gel method, which uses a copolymer to create pores in the structure of CaSiO3. To improve the magnetic properties of the core-shell structure, different percent of Fe ions (0%, 5%, and 10%) are doped onto the calcium silicate structure; as for 10% Fe, i.e., ZnMnFe2O4@Fe10–CaSiO3, saturation magnetization and coercive magnetic field are 34.543 emu/g and 1Oe, respectively. In this configuration of nanocomposite, the pore volume and superparamagnetic property increase simultaneously. In addition, the core-shell mesoporous ZnMnFe2O4@Fe–CaSiO3 nanocomposite reveals comparable mesoporous channels (3.4–6 nm), while the amorphous structure of CaSiO3 has not been changed. These core-shell mesoporous superparamagnetic nanocomposites are evaluated in terms of drug loading and release using epirubicin (EPI) as a model drug. It is found that the increase of iron ions improves the capacity to stabilize the pH environment. Additionally, the mesoporous Fe–CaSiO3 nanostructures demonstrate a sustained drug release property that could be used in local drug delivery therapy. Therefore, these mesoporous superparamagnetic nanostructures would be a promising multifunctional platform for local drug delivery, magnetic resonance imaging, magnetic hyperthermia, and bone tissue regeneration.

Verteporfin-loaded sutureless composite barrier: A novel approach to peritendinous adhesion prevention

Peritendinous adhesion is one of the most common postoperative or posttraumatic complications of tendon injury, which severely limits functional rehabilitation and raises the risk of re-rupture. This study prepared a multifunctional composite composed of a “sandwich” electrospun nanofibrous membrane with sustained drug release property and adhesives for sutureless application. The composite was assessed here through microscopic, spectroscopic, wettability, rheological, mechanical, and drug release analyses. The results of these characterizations are consistent with the characteristics of anti-adhesion biomaterials. In addition, the anti-adhesion effectiveness was demonstrated in fibroblasts and rats. Briefly, the composite not only decreased the proliferation, viability, and penetration of fibroblasts but also repressed cell spreading on the material surface by regulating Yes-associated protein (YAP) and inhibited oxidative stress by scavenging reactive oxygen species (ROS) simultaneously in vitro. Meanwhile, histological analysis, functional tests, gross observation, and protein analysis in vivo showed that composite was effective in reducing tendon adhesion formation. Hence, we draw the conclusion that our composite can protect tendons from peritendinous adhesion after injury and provide a new direction for future application of peritendinous anti-adhesion.

A mussel-inspired multifunctional hydrogel reinforced by bacterial cellulose for wound healing: sustained drug release, enhanced adhesion and self-healing property

A mussel-inspired multifunctional hydrogel reinforced by bacterial cellulose for wound healing: sustained drug release, enhanced adhesion and self-healing property

Development of polylactic-co-glycolic acid-polyethylene glycol nanoparticles as drug carriers to promote wound healing

Impaired wound healing is a common complication of orthopedic surgery and poses a difficult challenge in the clinic. Fibroblasts are thought to play a significant role in wound healing, and can be positively affected by low concentrations of rapamycin; however, rapamycin is cytotoxic at higher concentrations. To address this issue, a RAPA/PLGA-PEG drug delivery system was constructed in this study to maintain low concentrations of rapamycin. The results showed that the nanoparticles were stable, had good sustained drug release properties and were able to reduce the toxicity of rapamycin to fibroblasts. These findings suggest that RAPA/PLGA-PEG nanoparticles can reduce the cytotoxicity of rapamycin and may be a potential clinical treatment for impaired wound healing.

Recent progress of hydrogel-based local drug delivery systems for postoperative radiotherapy.

Surgical resection and postoperative radiotherapy remained the most common therapeutic modalities for malignant tumors. However, tumor recurrence after receiving such combination is difficult to be avoided because of high invasiveness and radiation resistance of cancer cells during long-term therapy. Hydrogels, as novel local drug delivery systems, presented excellent biocompatibility, high drug loading capacity and sustained drug release property. Compared with conventional drug formulations, hydrogels are able to be administered intraoperatively and directly release the entrapped therapeutic agents to the unresectable tumor sites. Therefore, hydrogel-based local drug delivery systems have their unique advantages especially in sensitizing postoperative radiotherapy. In this context, classification and biological properties of hydrogels were firstly introduced. Then, recent progress and application of hydrogels for postoperative radiotherapy were summarized. Finally, the prospects and challenges of hydrogels in postoperative radiotherapy were discussed.

Topical Application of Linezolid–Loaded Chitosan Nanoparticles for the Treatment of Eye Infections

Linezolid (LZ) loaded chitosan-nanoparticles (CSNPs) was developed by the ionic-gelation method using Tripolyphosphate-sodium as a crosslinker for topical application for the treatment of bacterial eye infections. Particles were characterized by Zeta-Sizer (Malvern Nano-series). TEM was used for structural morphology. Encapsulation and drug loading were estimated by measuring the unencapsulated drug. In-vitro drug release in STF (pH 7) was performed through a dialysis membrane. Storage stability of LZ-CSNPs was checked at 25 °C and 40 °C for six months. The antimicrobial potency of NPs was evaluated on different Gram-positive strains. Ocular irritation and pharmacokinetic studies were completed in rabbits. Ex-vivo transcorneal permeation of the drug was determined through the rabbit cornea. Ionic interaction among the oppositely charged functional groups of CS and TPP generated the CSNPs. The weight ratio at 3:1, wt/wt (CS/TPP) with 21.7 mg of LZ produced optimal NPs (213.7 nm with 0.387 of PDI and +23.1 mV of ZP) with 71% and 11.2% encapsulation and drug loading, respectively. Around 76.7% of LZ was released from LZ-AqS within 1 h, while 79.8% of LZ was released from CSNPs at 12 h and 90% at 24 h. The sustained drug release property of CSNPS was evaluated by applying kinetic models. The linearity in the release profile suggested that the release of LZ from CSNPs followed the Higuchi-Matrix model. LZ-CSNPs have shown 1.4 to 1.6-times improved antibacterial activity against the used bacterial strains. The LZ-CSNPs were "minimally-irritating" to rabbit eyes and exhibited 4.4-times increased transcorneal permeation of LZ than from LZ-AqS. Around 3-, 1.2- and 3.1-times improved Tmax, Cmax, and AUC0-24 h, respectively were found for LZ-CSNPs during the ocular pharmacokinetic study. AqS has shown 3.1-times faster clearance of LZ. Conclusively, LZ-CSNPs could offer a better alternative for the prolonged delivery of LZ for the treatment of bacterial infections in the eyes.

A Double-Layer Hydrogel Dressing with High Mechanical Strength and Water Resistance Used for Drug Delivery.

Hydrogel dressings provide a moist wound healing environment, absorb the exudates of the wound, and have better biocompatibility than traditional dressings. However, it is still difficult to meet the needs of modern medicine due to the defects in drug burst release, weak mechanical strength, and poor water retention. To solve these problems, we developed a double-layer (DL) hydrogel based on β-cyclodextrin polymer (β-CDP), poly(vinyl alcohol) (PVA), and carboxymethyl cellulose sodium (CMC) via a layer-by-layer method. Inspired by natural coconut, this hydrogel consisted of a drug release layer (DRL) and a mechanical support layer (MSL). In our design, the introduction of β-CDP into the DRL slowed the drug release rate of the DL hydrogel. Furthermore, the mechanical strength of the hydrogel was improved by immersing the MSL in a calcium chloride/boric acid solution. Combining these two layers, the tensile strength and elongation at break of the DL hydrogel reached 1504 kPa and 400%, respectively. More interestingly, the release mechanism of DL hydrogel conformed to the diffusion-relaxation-erosion model, which was different from traditional hydrogel dressings. Therefore, the as-prepared DL structure represents a feasible solution for fabricating high-performance mechanical hydrogel dressings with sustained drug release properties, and the DL hydrogel has potential to be used for medical dressings applied in daily life.

Cupriavidus necator-Produced Polyhydroxybutyrate/Eudragit FS Hybrid Nanoparticles Mitigates Ulcerative Colitis via Colon-Targeted Delivery of Cyclosporine A.

Polyhydroxybutyrate (PHB) has emerged as a novel material for replacing various plastics used in the medical field. However, its application as a drug-delivery carrier for colitis-targeted delivery has not been explored. In this study, we used biosynthesized PHB combined with Eudragit FS (EFS) and cyclosporine A (CSA) to develop pH-responsive controlled CSA-releasing nanoparticles (CSA-PENPs) for colitis-targeted drug delivery and demonstrated its enhanced therapeutic efficacy in a dextran sulfate sodium (DSS)-induced murine colitis model. PHB was successfully biosynthesized in the bacterium Cupriavidus necator, as demonstrated by 1H-NMR and FT-IR analyses. CSA-PENPs were fabricated via the oil-in-water emulsion solvent evaporation method. Owing to the potent pH-responsive and sustained drug release properties provided by PHB and EFS, CSA-PENPs could deliver a sufficient amount of CSA to inflamed tissues in the distal colon; in contrast, CSA-loaded EFS nanoparticles displayed premature burst release before reaching the target site. Due to enhanced CSA delivery to colitis tissues, CSA-PENPs exhibited potent anti-inflammatory effects in the DSS-induced murine colitis model. Overall, CSA-PENPs could be a promising drug-delivery system for treating ulcerative colitis.

Poly(trimethylene carbonate)‐b‐poly(ethylene glycol) diblock copolymer micelles for hydrophobic drug delivery: The effect of hydrophilic/hydrophobic segment length on micellar properties and drug loading

AbstractThe encapsulation and release of hydrophobic drugs from polymersomes are of great importance in drug delivery. A significant challenge is to enhance the encapsulation capacity of finding better drug‐polymer compatibility. Herrin, poly(trimethylene carbonate)‐b‐poly(ethylene glycol) (PTMC‐PEG) diblock copolymers were successfully synthesized by ring opening polymerization of trimethylene carbonate using monomethoxy poly(ethylene glycol) (mPEG) as macro‐initiator and stannous octoate as catalyst. The resulting diblock copolymer were characterized by 1H NMR, FTIR, GPC, and DSC techniques. Blank and paclitaxel (PTX) loaded micelles was prepared by co‐solvent evaporation method and characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). The influence of hydrophilic/hydrophobic segment length to drug loading and release was explored. All micelles have the sustained hydrophobic drug release properties of the micelles. Moreover, the cytotoxicity of micelles was evaluated by MTT and live‐dead cell staining assay using L929 cell lines, showing the good biocompatibility. Therefore, PTMC‐PEG micelles could be a suitable material for the loading and releasing of hydrophobic drugs.

Biointerfacial giant capsules with high paclitaxel loading and magnetic targeting for breast tumor therapy

High drug loading, targeted delivery, prolonged drug release, and low systemic toxicity are effective weapons for hydrophobic drug delivery systems to solve serious concerns in poor water-solubility and toxicity of paclitaxel (PTX). Herein, we reported that biointerfacial giant multilayer microcapsules (BGMs) with the feature of high-density drug loading and high-efficiency magnetic delivery were fabricated templated by PTX-liposome-microbubble complex using the layer-by-layer self-assembly (LbL) technique. The drug loading capacity of BGMs was improved by optimizing the structure of microbubbles and capsules to increase the PTX-contained layers, and the resultant BGMs exhibited high drug loading content (50.56 ± 0.09 %) and sustained drug release properties. The BGMs with an average diameter of 74.1 ± 12.1 µm and an average thickness of 275.5 ± 48.4 nm contained abundant magnetic nanoparticles (MNPs) in their cavity, which endowed these capsules with outstanding magnetic properties and fast magnetophoretic velocity in the blood (∼0.3 mm/s, ▽B = 1 T/mm). Moreover, both in vitro and in vivo studies demonstrated that the biocompatible PTX-loaded magnetic BGMs (Capsule@PLMPPL) caused notable death (71.3 ± 2.9 %) of 4 T1 breast cancer cells through PTX diffusion, capsules degradation, and subsequent endocytosis by cancer cells, and ultimately effectively inhibited tumor growth. In general, the developed BGM with good deformability and degradation was the first reported giant polyelectrolyte capsule to be used in tumor therapy, which could notably improve the therapeutic efficacy of PTX while reducing its side effects.