Sustained Drug Release Behavior Research Articles

An injectable composite hydrogel containing polydopamine-coated curcumin nanoparticles and indoximod for the enhanced combinational chemo-photothermal-immunotherapy of breast tumors

The complexity and compensatory evolution of tumors weaken the effectiveness of single antitumor therapies. Therefore, multimodal combination therapies hold great promise in defeating tumors. Herein, we constructed a multi-level regulatory co-delivery system based on chemotherapy, phototherapy, and immunotherapy. Briefly, curcumin (Cur) was prepared as nanoparticles and coated with polydopamine (PDA) to form PCur-NPs, which along with an immune checkpoint inhibitor (indoximod, IND) were then loaded into a thermosensitive Pluronic F127 (F127) hydrogel to form a multifunctional nanocomposite hydrogel (PCur/IND@Gel). The in situ-formed hydrogel exhibited excellent photothermal conversion efficiency and sustained drug release behavior both in vitro and in vivo. In addition, PCur-NPs showed enhanced cellular uptake and cytotoxicity under NIR laser irradiation and induced potent immunogenic cell death (ICD). After intratumoral injection of PCur/IND@Gel, significant apoptosis in 4T1 tumors was induced, dendritic cells in lymph nodes were highly activated, potent CD8+ and CD4+ antitumor immune responses were elicited and regulative T cells in tumors were significantly reduced, which notably inhibited the tumor growth and prolonged the survive time of 4T1 tumor-bearing mice. Therefore, this injectable nanocomposite hydrogel is a promising drug co-delivery platform for chemo-photothermal-immunotherapy of breast tumors.

Mechanical properties and sustained drug release behavior of selective laser melted Ti6Al4V scaffolds modified using gentamicin loaded chitosan

Mechanical properties and sustained drug release behavior of selective laser melted Ti6Al4V scaffolds modified using gentamicin loaded chitosan

Synthesis and evaluation of berberine loaded chitosan nanocarrier for enhanced in-vitro antioxidant and anti-inflammatory potential

Berberine, a naturally occurring isoquinoline plant alkaloid molecule, finds application in traditional medicine due to its extensive pharmacological effects but it cannot be clinically exploited to its fullest as it possesses poor water solubility and bioavailability. In order to address this issue, we have synthesized berberine loaded chitosan nanoparticles (BCNPs) using DMSO as surfactant and chitosan as polymer using modified ionic complexation approach and optimized the process utilizing central composite design. The BCNPs were empirically assessed for various parameters such as particle size distribution, zeta potential, drug encapsulation efficiency and surface morphology using established methodologies. BCNPs were additionally assessed for in-vitro antibacterial activity, in-vitro antioxidant activity, in-vitro anti-inflammatory activity, and sustained drug release behavior using established techniques. Experimental results showed that chitosan at a concentration of 0.05 % (w/v) and DMSO at a concentration of 1 % (v/v) successfully generated nanoparticles with a spherical shape with size ranging from 20 to 60 nm and exhibited a stabilizing zeta potential of 26.1 mV. Additionally, they had a high encapsulation effectiveness of 94.01 %. Sustained release was observed with 74.30 % berberine released in 48 h, respectively from BCNPs. The antimicrobial assays reveal that BCNPs exhibit superior antibacterial effectiveness against all bacterial strains compared to berberine alone as determined by the agar well diffusion method. The BCNPs also exhibited a substantial enhancement in DPPH activity and a greater percentage of protection compared to berberine. In summary, our research suggests that chitosan nanocarrier can enhance the solubility of berberine and facilitate the development of novel naturally-derived antioxidants and anti-inflammatory compounds. This study will further provide an insight into the future development of natural drug discovery.

Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis reduce inflammation and counteract oxidative stress and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.

Spray-Dried Mucoadhesive Re-dispersible Gargle of Chlorhexidine for Improved Response Against Throat Infection: Formulation Development, In Vitro and In Vivo Evaluation.

Drug delivery to the buccal mucosa is one of the most convenient ways to treat common mouth problems. Here, we propose a spray-dried re-dispersible mucoadhesive controlled release gargle formulation to improve the efficacy of chlorhexidine. The present investigation portrays an approach to get stable and free-flowing spray-dried porous aggregates of chlorhexidine-loaded sodium alginate nanoparticles. The ionic gelation technique aided with the chlorhexidine's positive surface charge-based crosslinking, followed by spray drying of the nanoparticle's dispersion in the presence of lactose- and leucine-yielded nano-aggregates with good flow properties and with a size range of about 120-350nm. Provided with the high entrapment efficiency (87%), the particles showed sustained drug release behaviors over a duration of 10h, where 87% of the released drug got permeated within 12h. The antimicrobial activity of the prepared formulation was tested on S. aureus, provided with a higher zone of growth inhibition than the marketed formulation. Aided with an appropriate mucoadhesive strength, this product exhibited extended retention of nanoparticles in the throat region, as shown by in vivo imaging results. In conclusion, the technology, provided with high drug retention and extended effect, could be a potential candidate for treating several types of throat infections.

Surfactant-free fabrication of curcumin-loaded emulsion coatings on titanium for biomedical applications

Biofunctional emulsion coatings of curcumin-loaded poly(ɛ-caprolactone)/polyvinyl alcohol-hydroxyapatite (Cur-loaded PCL/PVA-HA) were developed on the titanium (Ti) plates without using any surfactant. Firstly, stable oil-in-water emulsions with different water/oil (W/O) ratios (9:1, 7:1, 5:1 and 3:1) were prepared by using the uniform PVA-HA slurry as a water phase and the Cur-loaded PCL solution as an oil phase. The diameter of the oil droplets in those emulsions mostly ranged from 4 to 6 µm. Subsequently, the emulsions were formulated into coatings on Ti through a spin-coating process. The obtained emulsion coatings consisted of Cur-loaded PCL microspheres that were evenly embedded in the PVA-HA matrix, and their phase composition was identified by the FT-IR analysis. The emulsion coatings were hydrophilic and displayed a gradual increase in water contact angles with the decrease of the W/O ratio. Moreover, abundant bone-like apatite aggregates were formed on the emulsion coatings, suggesting their excellent in vitro bioactivity. In addition, the emulsion coatings exhibited a sustained drug release behavior within 2–48 h, and the release process was mainly controlled by diffusion. The present study provides a new perspective on green and facile fabrication of functional emulsion coatings.

ROS-responsive thermosensitive polypeptide hydrogels for localized drug delivery and improved tumor chemoimmunotherapy.

In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. The hydrogel demonstrated controllable degradation and sustained drug release behavior according to the concentration of ROS in vitro. Following intratumoral injection into mice bearing B16F10 melanoma, the Dox/R848/aPD-1 co-loaded hydrogel effectively inhibited tumor growth, prolonged animal survival time and promoted anti-tumor immune responses with low systemic toxicity. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogel exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective anti-tumor treatment and suppression of tumor recurrence.

Development of implantable drug delivery system of embelin for the treatment of breast cancer

Embelin is a traditional herbal medicine that exhibits anti-cancer effects in human breast cancer cells. However, the therapeutic effect of Embelin as Implantable Drug Delivery System is not yet determined. Embelin is having drawbacks like poor bioavailability and toxicity in systemic circulation, so we opt for Implantable Drug Delivery System. In this study, we optimised, developed and evaluated the Implantable Drug Delivery System of Embelin as pellets. The prime objective of the study is to prolong the drug release as much as possible using a combination of naturally occurring biodegradable polymer such as Guar gum, Chitosan, Xanthan gum, Locust bean gum. In this study, integration of Embelin and Chitosan was achieved via Granulation, with the aid of Guar gum as an excipient, followed by Extrusion /spheronisation. In vitro drug release study revealed the chitosan blended Embelin loaded implant possesses a longer, yet steadier, sustained drug release behaviour than the other three bio polymeric implants. It exhibits prolonged drug release of up to nine days and Korsmeyer’s-peppas plot were exhibited.

Sustained drug release behavior of captopril-incorporated chitosan/carboxymethyl cellulose biomaterials for antihypertensive therapy

Captopril (CTP) is an oral drug widely used to treat high blood pressure and congestive heart failure. In this study, CTP-incorporated biomaterials for antihypertensive therapy were synthesized from chitosan, carboxymethyl cellulose, and plasticizers. The physicochemical properties of the prepared biomaterials were characterized using FE-SEM, FT-IR analysis, and physical properties. CTP release experiments were carried out in buffer solutions at various pH values and temperatures. Results indicated that above 99.0 % of CTP was released within 180 min. Optimization of the experimental conditions for CTP release was analyzed by using response surface methodology (RSM). Results of CTP release through artificial skin indicated that CTP was continuously released above 95.0 % from the prepared biomaterials for 36.0 h. The CTP release mechanisms into a buffer and through artificial skin followed pseudo-Fickian diffusion mechanism and non-Fickian diffusion mechanisms, respectively. Moreover, angiotensin-converting enzyme (ACE) inhibition (related to cardiovascular disease) via the released CTP clearly reveals that the prepared biomaterials have a high potential as a transdermal drug delivery agent in antihypertensive therapy.

Stimuli-responsive “theranostic” nanocomposite hydrogels based on β-cyclodextrin containing Fe3O4 and Bi2O3 nanoparticles for targeted delivery of methotrexate

The present study aimed to design and development of novel “theranostic” hydrogels-based drug delivery system (DDSs) composed of beta-cyclodextrin (β-CD), poly(N,N´-dimethylamino)ethyl methacrylate) (PDMAEMA), and Fe3O4 and Bi2O3 nanoparticles (NPs). Methotrexate (MTX) was loaded into the fabricated hydrogels as an anti-cancer drug. Drug encapsulation efficiencies for S1 and S2 samples were obtained as 77.74 and 81 %, respectively. In vitro drug release study verified pH-dependent and sustained drug release behavior of the formulated S1/MTX and S2/MTX. Cytocompatibilities of the hydrogels were approved using MTT-assay on MCF-7 cells. In contrast, the drug-loaded hydrogels showed time- and concentration-dependence cytotoxicities. As MTT-assay results, IC50 in time period of 48 h for free MTX, S1/MTX, and S2/MTX were quantified as 55, 27 and 27 µgmL−1 based on concentration of MTX. Therefore, S1/MTX and S2/MTX possesses higher anti-cancer activities owing to sustained and “smart” release of drug that could reduce drug dosage and side effects. The presence of Fe3O4 NPs and Bi2O3 NPs in the hydrogels allows diagnosis by MRI and CT, respectively. In addition, Bi2O3 NPs is suggested as efficient X-ray radiosensitizer for increasing the efficiency of radiotherapy. Therefore, the fabricated hydrogels have potential for synergistic chemoradiotherapy and can be exploited in medical imaging.

Curcumin-loaded hydroxyapatite nanoparticles for enriched removal of organic pollutants and inhibition of dual-species biofilm formation

The resistance of staphylococcus aureus and Acinetobacter baumannii to antimicrobial agents results in chronic infections, making removing contaminants from wastewater essential for environmental remediation. Removing hazardous pollutants from wastewater and inhibiting biofilm formation is important for environmental remediation. This study effectively built biocompatible curcumin-loaded hydroxyapatite nanoparticles (Cur-HAp NPs) using a simple in-situ precipitation technique. Various analytical characterization techniques were used to evaluate the structural, morphological, and chemical composition of the synthesized NPs. Combining a highly bioactive natural curcumin pigment with hydroxyapatite NPs could maintain its pharmacological activity and exhibit a sustained release profile of curcumin. The antibiofilm activities against single and mixed dual species of S. aureus and A. baumannii were evaluated using crystal violet staining techniques. Excellent antibiofilm activities were demonstrated by Cur-HAp NPs against S. aureus, A. baumannii, and mixed dual species, with respective efficiency percentages of 76.7, 85.6, and 68.8 % inhibition upon treatment, respectively. In addition, Cur-HAp NPs demonstrated excellent dye adsorption against Congo red dye by approximately 95.6 %. Cur-HAp could absorb up to 112.4 mg/g of dye at a time. Negative ΔG value (−1.372 kJ mol−1) indicates the spontaneous and feasible dye absorption onto Cur-HAp. The Langmuir adsorption isotherm and pseudo-second-order equation provided the best fit for the Cur-HAp NPs. Therefore, the sustained drug release behavior of Cur-HAp NPs is a promising candidate for combatting antibiofilm activity and dye removal capacity.

A sustained‐release gel film based on chitosan for treating cutaneous candidiasis

AbstractHydrogels have been widely used in wound dressings owing to their biocompatibility and bacteriostatic properties. In this study, a chitosan‐citric acid gel film was prepared using chitosan as the raw material and citric acid as the acid solvent and cross‐linking agent. In addition, to increase the antibacterial effect of the gel film, ketoconazole/β‐cyclodextrin inclusion complex was prepared by inclusion technology and added to the gel film to prepare a chitosan‐citric acid sustained‐release gel film loaded with ketoconazole/β‐cyclodextrin inclusion complex for treating cutaneous candidiasis. The physical and chemical properties of the chitosan‐citric acid gel films were investigated using infrared spectroscopy, x‐ray diffraction, water vapor transmittance test, thermal analysis, and swelling tests. Drug release, antibacterial, and toxicity tests of the chitosan‐citric acid gel film loading with ketoconazole/β‐cyclodextrin inclusion complex were carried out in vitro. The composite film showed good sustained drug release behavior, antibacterial effects, and biocompatibility in vitro. These results support that the chitosan‐citric acid hydrogel has great potential as a gel wound dressing for the treatment of cutaneous candidiasis.

Microarray needles comprised of arginine-modified chitosan/PVA hydrogel for enhanced antibacterial and wound healing potential of curcumin

Wound healing is a multifaceted and complex process that includes inflammation, hemostasis, remodeling, and granulation. Failures in any link may cause the healing process to be delayed. As a result, wound healing has always been a main research focus across the entire medical field, posing significant challenges and financial burdens. Hence, the current investigation focused on the design and development of arginine-modified chitosan/PVA hydrogel-based microneedles (MNs) as a curcumin (CUR) delivery system for improved wound healing and antibacterial activity. The substrate possesses exceptional swelling capabilities that allow tissue fluid from the wound to be absorbed, speeding up wound closure. The antibacterial activity of MNs was investigated against S. aureus and E. coli. The results revealed that the developed CUR-loaded MNs had increased antioxidant activity and sustained drug release behavior. Furthermore, after being loaded in the developed MNs, it revealed improved antibacterial activity of CUR. Wound healing potential was assessed by histopathological analysis and wound closure%. The observed results suggest that the CUR-loaded MNs greatly improved wound healing potential via tissue regeneration and collagen deposition, demonstrating the potential of developed MNs patches to be used as an effective carrier for wound healing in healthcare settings.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress. Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis. Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved. Herein, we reported a nanotransdermal delivery system composed of all-trans retinoic acid (TRA), triphenylphosphine (TPP)-modified cerium oxide (CeO2) nanoparticles, flexible nanoliposomes and gels (TCeO2-TRA-FNL-Gel). The results revealed that TCeO2 synthesized by the anti-micelle method, with a size of approximately 5 nm, possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species (ROS). TCeO2-TRA-FNL prepared by the film dispersion method, with a size of approximately 70 nm, showed high drug encapsulation efficiency (>96%). TCeO2-TRA-FNL-Gel further showed sustained drug release behaviors, great transdermal permeation ability, and greater skin retention than the free TRA. The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO2-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells. The results of in vivo imiquimod (IMQ)-induced model indicated that TCeO2-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms. In summary, the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Injectable multifunctional carboxymethyl chitosan/hyaluronic acid hydrogel for drug delivery systems

Injectable hydrogels with notable mechanical properties and self-healing ability are promising carriers for use as a drug delivery system. Here, adipic acid dihydrazide (ADH) and calcium ions (Ca2+) were introduced into quaternary ammonium carboxymethyl chitosan and aldehyde-modified hyaluronic acid hydrogels (QCS + OHA). The hydrogels were synthesized through the interaction of the Schiff bases (imine bonds, acylhydrazone bonds) and coordination bonds via a facile one-step approach. The gelation time (∼54 s) ensured excellent injectability. The QCS + OHA + ADH + Ca2+ hydrogel had notable mechanical properties (compressive stress up to 896.30 KPa), good self-healing ability (up to 94 %), good pH responsiveness, and excellent antibacterial properties. In addition, the QCS + OHA + ADH + Ca2+ hydrogel had a high drug loading capacity (121.3 mg/g) and sustained drug release behaviour (≥120 h). The results of cytotoxicity tests showed a high cell proliferation rate (up to 98 %) and good cytocompatibility. In summary, this work presents an injectable and self-healing pH-responsive hydrogel that can be used as a carrier for drug delivery systems.

Chitosan-grafted Microspherical Loaded In-situ Gels for Enhanced Transdermal Delivery of Roxithromycin: In-vitro/Ex-vivo Assessment

Background: Atleast once in life everyone experience different kinds of dermal diseases and the conventional dosage forms having a high rate of side effects. The discussed method is a better and alternative approach in case of patients’ compliance and sustained drug release. Objective: The objectives of this study are to prepare solid dispersion for enhancement of solubility of roxithromycin, encapsulation of solid dispersion into microspheres, decreased dose frequency, sustained release and incorporation of microspheres in in situ gel for easy utilization and adherence over the skin in microbial infection. Methods: Solid dispersion of roxithromycin and HPMC at a ratio of 1:1 was prepared by the melting method, and solubility was measured by in vitro dissolution rate. On the basis of 3² factorial design, 9 different formulations were evaluated by % drug release, particle size, and % entrapment efficiency. Lastly, in situ gel was prepared by a cold method, which was evaluated through gelling time and temperature; in vitro gelation method. Results: The solid dispersion was found to have a 1.3 times higher solubility than pure roxithromycin as proven by in vitro drug release. Whereas, microsphere MF-9 was selected as the best formulation via drug release (87.81%), entrapment efficiency (91.223%), % yield (86.681), and particle size (110μm). In-situ gel MIG-5 was selected as the best formulation on the basis of drug content (89.326±0.564), viscosity (9551.666±6.233), and gelling time (25.333±2.054). Conclusion: Solid dispersion was prepared successfully with higher solubility than the pure drug. Microspheres have shown sustained drug release and in situ gels have a good adhesive property and MIG-5 further enhances the sustained drug release behaviour.

Fabrication of Electrospun PLA-nHAp Nanocomposite for Sustained Drug Release in Dental and Orthopedic Applications.

This study describes the fabrication of nanocomposites using electrospinning technique from poly lactic acid (PLA) and nano-hydroxyapatite (n-HAp). The prepared electrospun PLA-nHAP nanocomposite is intended to be used for drug delivery application. A hydrogen bond in between nHAp and PLA was confirmed by Fourier transform infrared (FT-IR) spectroscopy. Degradation study of the prepared electrospun PLA-nHAp nanocomposite was conducted for 30 days both in phosphate buffer solution (PBS) of pH 7.4 and deionized water. The degradation of the nanocomposite occurred faster in PBS in comparison to water. Cytotoxicity analysis was conducted on both Vero cells and BHK-21 cells and the survival percentage of both cells was found to be more than 95%, which indicates that the prepared nanocomposite is non-toxic and biocompatible. Gentamicin was loaded in the nanocomposite via an encapsulation process and the in vitro drug delivery process was investigated in phosphate buffer solution at different pHs. An initial burst release of the drug was observed from the nanocomposite after 1 to 2 weeks for all pH media. After that, a sustained drug release behavior was observed for the nanocomposite for 8 weeks with a release of 80%, 70% and 50% at pHs 5.5, 6.0 and 7.4, respectively. It can be suggested that the electrospun PLA-nHAp nanocomposite can be used as a potential antibacterial drug carrier for sustained drug release in dental and orthopedic sector.

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens

Posterior capsule opacification (PCO) is the most common long-term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention, which provides physical barriers and biological inhibition, respectively, can block the migration, proliferation, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. Herein, a novel indomethacin-eluting IOL (INDOM-IOL) with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention. Indomethacin (INDOM), an ophthalmic non-steroidal anti-inflammatory drug (NSAID) used for postoperative ocular inflammation, was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2 (COX-2) and EMT markers, including alpha-smooth muscle actin (α-SMA) and cyclin D1, but also promote the autophagy activation in LECs. Additionally, autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs. The novel IOL, serving as a drug delivery platform, could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days. In the rabbit PCO model, the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects. In summary, indomethacin is an effective pharmacological intervention in PCO prophylaxis, and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property, which provided a promising approach for PCO prophylaxis in clinical application.

Thermosensitive selenium hydrogel boosts antitumor immune response for hepatocellular carcinoma chemoradiotherapy

Hepatocellular carcinoma (HCC) possesses high mortality rate and becomes the third most common cause of cancer death. Searching new therapeutic strategies for HCC are still urgently needed. In situ thermosensitive hydrogels loading with chemotherapeutics have attracted increasing attention for HCC due to their superior advantages including high drug loading and sustained drug release behavior. Herein, we developed a novel in situ injection thermosensitive hydrogel system based on Poloxamer 407 (P407) and selenium nanoparticle loading with DOX (PPS-SeNPs@DOX) for localized synergistic chemoradiotherapy of HCC. The synthesized PPS-SeNPs@DOX hydrogel system showed a better phase transition temperature at 32 ℃, and the mechanical properties were not affected under X-ray irradiation, which suggests the stability of the synthesized hydrogel. The localized injection of PPS-SeNPs@DOX combined with radiotherapy was found to significantly suppress HepG2 tumors growth in vivo, as evidenced by the decreased tumor volume, tumor weight and Ki67 expression. Furthermore, the synergistic anticancer effects in orthotopic Hepa1-6 tumors were also found in the combination treatment of PPS-SeNPs@DOX and X-ray irradiation with the involvement of antitumor immunity activation accompanied by the upregulated population of CD8+ T, M1 and NK1.1 cells and downregulated population of Gr1 cells after single in situ injection. Taken together, this study presents a novel in situ injection thermosensitive hydrogel system for the chemoradiotherapy of HCC, which may provide a solid foundation for designing local delivery platform for unresectable HCC therapy.

Rapidly separable microneedle patch for the controlled and sustained release of 5-fluorouracil

5-Fluorouracil (5-FU) is frequently used in the treatment of tumors and swollen tissues. However, traditional administration methods can result in poor patient compliance and require to administrate frequently due to the short T1/2 of 5-FU. Herein, the 5-FU@ZIF-8 loaded nanocapsules were prepared using multiple emulsion solvent evaporation methods to enable the controlled and sustained release of 5-FU. To decrease the drug release rate and enhance patient compliance, the obtained pure nanocapsules were added to the matrix to fabricate rapidly separable microneedles (SMNs). The entrapment efficiency (EE%) of 5-FU@ZIF-8 loaded nanocapsules was in the range of 41.55–46.29 %, and the particle size of ZIF-8, 5-FU@ZIF-8, and 5-FU@ZIF-8 loaded nanocapsules were 60 nm, 110 nm, and 250 nm respectively. According to the release study in vivo and in vitro, we concluded that 5-FU@ZIF-8 nanocapsules could achieve the sustained release of 5-FU and that the burst release of nanocapsules could be elegantly handled by incorporating nanocapsules into the SMNs. What's more, the use of SMNs could improve patient compliance due to the rapid separation of needles and backing of SMNs. The pharmacodynamics study also revealed that the formulation would be a better choice for the treatment of scars due to the advantages of painlessness, separation ability, and high delivery efficiency. In conclusion, the SMNs containing 5-FU@ZIF-8 loaded nanocapsules could serve as a potential strategy for some skin diseases therapy with controlled and sustained drug release behavior.