A single local delivery of paclitaxel and nucleic acids via an immunoactive polymer eliminates tumors and induces antitumor immunity.

Despite recent advances in cancer therapy, hard-to-reach, unidentified tumors remain a significant clinical challenge. A promising approach is to treat locatable and accessible tumors locally and stimulate antitumor immunity in situ to exert systemic effects against distant tumors. We hypothesize that a carrier of immunotherapeutics can play a critical role in activating antitumor immunity as an immunoadjuvant and a local retainer of drug combinations. Here, we develop a polyethyleneimine-lithocholic acid conjugate (2E'), which forms a hydrophobic core and cationic surface to codeliver hydrophobic small molecules and anionic nucleic acids and activates antigen-presenting cells via the intrinsic activities of 2E' components. 2E' delivers paclitaxel and small-interfering RNA (siRNA) targeting PD-L1 (or cyclic dinucleotide, [CDN]) to induce the immunogenic death of tumor cells and maintain the immunoactive tumor microenvironment, and further activates dendritic cells and macrophages, leveraging the activities of loaded drugs. A single local administration of 2E' or its combination with paclitaxel and PD-L1­targeting siRNA or CDN induces strong antitumor immunity, resulting in immediate regression of large established tumors, tumor-free survival, an abscopal effect on distant tumors, and resistance to rechallenge and metastasis in multiple models of murine tumors, including CT26 colon carcinoma, B16F10 melanoma, and 4T1 breast cancer. This study supports the finding that local administration of immunotherapeutics, when accompanied by the rationally designed carrier, can effectively protect the host from distant and recurrent diseases.

Self-assembled Pt(II) metallacycles enable precise cancer combination chemotherapy.

Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acid­functionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.

Tumor Microenvironment-Triggered Self-Adaptive Polymeric Photosensitizers for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) employs photosensitizers to convert nearby oxygen into toxic singlet oxygen (1O2) upon laser light irradiation, showing great potential as a noninvasive approach for tumor ablation. However, the therapeutic efficacy of PDT is essentially impeded by π-π stacking and the aggregation of photosensitizers. Herein, we propose a tumor microenvironment-triggered self-adaptive nanoplatform to weaken the aggregation of photosensitizers by selenium-based oxidation at the tumor site. The selenide units in a selenium-based porphyrin-containing amphiphilic copolymer (PSe) could be oxidized into hydrophilic selenoxide units, leading to the nanoplatform self-expansion and stretching of the distance between intramolecular porphyrin units. This process could provide a better switch to greatly reduce the aggregation of photosensitive porphyrin units, generating more 1O2 upon laser irradiation. As verified in a series of in vitro and in vivo studies, PSe could be efficiently self-adapted at tumor sites, thus significantly enhancing the PDT therapeutic effect against solid tumors and minimizing side effects.

On-Demand Opioid Effect Reversal with an Injectable Light-Triggered Polymer-Naloxone Conjugate.

Misuse of opioids can lead to a potential lethal overdose. Timely administration of naloxone is critical for survival. Here, we designed a polymer-naloxone conjugate that can provide on-demand phototriggered opioid reversal. Naloxone was attached to the polymer poly(lactic-co-glycolic acid) via a photocleavable coumarin linkage and formulated as injectable nanoparticles. In the absence of irradiation, the formulation did not release naloxone. Upon irradiation with blue (400 nm) light, the nanoparticles released free naloxone, reversing the effect of morphine in mice. Such triggered events could be performed days and weeks after the initial administration of the nanoparticles and could be performed repeatedly.

Shell-Sheddable Polymeric Micelles Alleviate Oxidative Stress and Inflammation for Enhanced Ischemic Stroke Therapy.

As a ROS scavenger, resveratrol exerts a neuroprotective effect by polarizing the M1 microglia to the anti-inflammatory M2 phenotype for ischemic stroke treatment. However, the obstruction of the blood-brain barrier (BBB) seriously impairs the efficacy of resveratrol. Herein, we develop a stepwise targeting nanoplatform for enhanced ischemic stroke therapy, which is fabricated by pH-responsive poly(ethylene glycol)-acetal-polycaprolactone-poly(ethylene glycol) (PEG-Acetal-PCL-PEG) and modified with cRGD and triphenylphosphine (TPP) on a long PEG chain and a short PEG chain, respectively. The as-designed micelle system features effective BBB penetration through cRGD-mediated transcytosis. Once entering the ischemic brain tissues and endocytosed by microglia, the long PEG shell can be detached from the micelles in the acidic lysosomes, subsequently exposing TPP to target mitochondria. Thus, the micelles can effectively alleviate oxidative stress and inflammation by enhanced delivery of resveratrol to microglia mitochondria, reversing the microglia phenotype through the scavenging of ROS. This work offers a promising strategy to treat ischemia-reperfusion injury.

Nanocarrier-Mediated Drug Delivery via Inhalational Route for Lung Cancer Therapy: A Systematic and Updated Review.

Lung cancer is one of the most severe lethal malignancies, with approximately 1.6 million deaths every year. Lung cancer can be broadly categorised into small and non-small-cell lung cancer. The traditional chemotherapy is nonspecific, destroys healthy cells and produces systemic toxicity; targeted inhalation drug delivery in conjunction with nanoformulations has piqued interest as an approach for improving chemotherapeutic drug activity in the treatment of lung cancer. Our aim is to discuss the impact of polymer and lipid-based nanocarriers (polymeric nanoparticles, liposomes, niosomes, nanostructured lipid carriers, etc.) to treat lung cancer via the inhalational route of drug administration. This review also highlights the clinical studies, patent reports and latest investigations related to lung cancer treatment through the pulmonary route. In accordance with the PRISMA guideline, a systematic literature search was carried out for published works between 2005 and 2023. The keywords used were lung cancer, pulmonary delivery, inhalational drug delivery, liposomes in lung cancer, nanotechnology in lung cancer, etc. Several articles were searched, screened, reviewed and included. The analysis demonstrated the potential of polymer and lipid-based nanocarriers to improve the entrapment of drugs, sustained release, enhanced permeability, targeted drug delivery and retention impact in lung tissues. Patents and clinical observations further strengthen the translational potential of these carrier systems for human use in lung cancer. This systematic review demonstrated the potential of pulmonary (inhalational) drug delivery approaches based on nanocarriers for lung cancer therapy.

Benefits and limitations of nanomedicine treatment of brain cancers and age-dependent neurodegenerative disorders.

The treatment of central nervous system (CNS) malignancies, including brain cancers, is limited by a number of obstructions, including the blood-brain barrier (BBB), the heterogeneity and high invasiveness of tumors, the inaccessibility of tissues for early diagnosis and effective surgery, and anti-cancer drug resistance. Therapies employing nanomedicine have been shown to facilitate drug penetration across the BBB and maintain biodistribution and accumulation of therapeutic agents at the desired target site. The application of lipid-, polymer-, or metal-based nanocarriers represents an advanced drug delivery system for a growing group of anti-cancer chemicals. The nanocarrier surface is designed to contain an active ligand (cancer cell marker or antibody)-binding structure which can be modified to target specific cancer cells. Glioblastoma, ependymoma, neuroblastoma, medulloblastoma, and primary CNS lymphomas were recently targeted by easily absorbed nanocarriers. The metal- (such as transferrin drug-loaded systems), polymer- (nanocapsules and nanospheres), or lipid- (such as sulfatide-containing nanoliposomes)-based nano-vehicles were loaded with apoptosis- and/or ferroptosis-stimulating agents and demonstrated promising anti-cancer effects. This review aims to discuss effective nanomedicine approaches designed to overcome the current limitations in the therapy of brain cancers and age-dependent neurodegenerative disorders. To accent current obstacles for successful CNS-based cancer therapy, we discuss nanomedicine perspectives and limitations of nanodrug use associated with the specificity of nervous tissue characteristics and the effects nanocarriers have on cognition.

Lipid polymer hybrid nanoparticles: a custom-tailored next-generation approach for cancer therapeutics.

Lipid-based polymeric nanoparticles are the highly popular carrier systems for cancer drug therapy. But presently, detailed investigations have revealed their flaws as drug delivery carriers. Lipid polymer hybrid nanoparticles (LPHNPs) are advanced core-shell nanoconstructs with a polymeric core region enclosed by a lipidic layer, presumed to be derived from both liposomes and polymeric nanounits. This unique concept is of utmost importance as a combinable drug delivery platform in oncology due to its dual structured character. To add advantage and restrict one's limitation by other, LPHNPs have been designed so to gain number of advantages such as stability, high loading of cargo, increased biocompatibility, rate-limiting controlled release, and elevated drug half-lives as well as therapeutic effectiveness while minimizing their drawbacks. The outer shell, in particular, can be functionalized in a variety of ways with stimuli-responsive moieties and ligands to provide intelligent holding and for active targeting of antineoplastic medicines, transport of genes, and theragnostic. This review comprehensively provides insight into recent substantial advancements in developing strategies for treating various cancer using LPHNPs. The bioactivity assessment factors have also been highlighted with a discussion of LPHNPs future clinical prospects.

Renal Clearable Catalytic 2D Au-Porphyrin Coordination Polymer Augmented Photothermal-Gas Synergistic Cancer Therapy.

As a gasotransmitter, carbon monoxide (CO) possesses antitumor activity by reversing the Warburg effect at higher concentrations. The targeted delivery of carbon monoxide-releasing molecules (CORMs) using nanomaterials is an appealing option for CO administration, but how to maintain CO above the threshold concentration in tumor tissue remains a challenge. Herein, a nanozyme-catalyzed cascade reaction is proposed to promote CO release for high-efficacy photothermal therapy (PTT)-combined CO therapy of cancer. A gold-based porphyrinic coordination polymer nanosheet (Au0 -Por) is synthesized to serve as a carrier for CORM. It also possesses excellent glucose oxygenase-like activity owing to ultrasmall zero-valent gold atoms on the nanosheet. The catalytically generated H2 O2 can efficiently catalyze CORM decomposition, which enables in situ generation of sufficient CO for gas therapy. In vivo, the Au0 -Por nanosheets-enhanced photoacoustic imaging (PAI) and fluorescence imaging collectively demonstrate high tumor-targeting efficiency and nanomaterial retention. Proven to have augmented therapeutic efficacy, the nanoplatform can also be easily degraded and excreted through the kidney, indicating good biocompatibility. Thus, the application of rational designed Au0 -Por nanosheet with facile approach and biodegradable property to PAI-guided synergistic gas therapy can provide a strategy for the development of biocompatible and highly effective gaseous nanomedicine.

Platinum Drug-Incorporating Polymeric Nanosystems for Precise Cancer Therapy.

Platinum (Pt) drugs are widely used in clinic for cancer therapy, but their therapeutic outcomes are significantly compromised by severe side effects and acquired drug resistance. With the emerging immunotherapy and imaging-guided cancer therapy, precise delivery and release of Pt drugs have drawn great attention these days. The targeting delivery of Pt drugs can greatly increase the accumulation at tumor sites, which ultimately enhances antitumor efficacy. Further, with the combination of Pt drugs and other theranostic agents into one nanosystem, it not only possesses excellent synergistic efficacy but also achieves real-time monitoring. In this review, after the introduction of Pt drugs and their characteristics, the recent progress of polymeric nanosystems for efficient delivery of Pt drugs is summarized with an emphasis on multi-modal synergistic therapy and imaging-guided Pt-based cancer treatment. In the end, the conclusions and future perspectives of Pt-encapsulated nanosystems are given.

NIR-Triggered On-Demand Nitric Oxide Release for Enhanced Synergistic Phototherapy of Hypoxic Tumor.

Hypoxia of tumor microenvironments is a major factor restricting tumor treatment, which causes progression and metastasis of tumor. The hypoxic tumor microenvironment not only makes the traditional treatment method, such as chemotherapy, ineffective but also hinders the O2-dependent treatments, such as photodynamic therapy (PDT). Recently, stimuli-responsive nitric oxide (NO) donors have attracted extensive research interest in hypoxic tumor treatment because the NO release process is O2-independent. Besides, NO can distribute more uniformly than drug molecules and more widely than the PDT-generated active species due to its strong diffusion ability (200 µm in cells) and long lifetime (2 s in cells). Encouraged by these advantages, a near infrared light-triggered NO release polymeric nanoplatform (P1-CapNO NPs) was constructed by a thermally sensitive NO release unit, a photothermal unit, and a hydrophilic polyethylene glycol unit. P1-CapNO NPs possess strong absorption in the NIR region (the wavelength of maximal absorption peak was 790 nm with a molar absorption coefficient of 2.4 × 105 M-1 cm-1), great photothermal conversion efficiency (23.8%), and NO release ability (the released NO concentration can reach 1.3 µM) under 808 nm laser irradiation. Owing to these advantages, the great synergistic antitumor effect can be achieved in vitro and in vivo even under the hypoxic environment. The synergistic therapeutic strategy in this work could bypass the obstacles caused by hypoxia in tumor treatment and provide a reference for building a NO-involved therapeutic platform.

Prototheca bovis in goats: Experimental mastitis and treatment with polypyrrole.

Prototheca bovis has been associated with several cases of mastitis in cattle but no record of intramammary infections has been reported in goats. This infection does not respond to available treatments and the disposal recommendation of affected animals cause great damage to the dairy industry. Alternatives for dealing with infections caused by Prototheca spp. are required worldwide. In vitro results suggest polypyrrole as promising molecule for combating this alga, because an algaecide effect was observed on tested Prototheca spp. isolates. Thus, this study evaluated goats as an experimental model for intramammary infection by P. bovis and a protocol for treating these animals with an intramammary polypyrrole solution. The possibility of P. bovis promoting an intramammary infection in goats was experimentally proven, demonstrating this species as an important model for studies involving algae mastitis. Furthermore, polypyrrole reduced the counts of Prototheca sp. in the analyzed samples, showing potential to fight this microorganism also in vivo. The results obtained in this study demonstrate the ability of P. bovis to colonize breast tissue in lactating goats and the highly soluble molecule of polypyrrole has potential use for the treatment of protothecosis.

Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against Neisseria gonorrhoeae in preclinical studies.

INTRODUCTION: Polyphenylene carboxymethylene (PPCM) is a condensation polymer that has both contraceptive and antimicrobial activity against several sexually transmitted viruses including HIV, herpes simplex virus, Ebola virus and SARS-CoV-2 in preclinical studies. PPCM, both as an active pharmaceutical ingredient (API) and in a vaginal gel formulation (Yaso-GEL), has an excellent safety profile. Here, we evaluated the efficacy of PPCM against Neisseria gonorrhoeae in vitro and in a gonorrhoea mouse model. METHODS: The minimal inhibitory concentration (MIC) of PPCM was determined against 11 N. gonorrhoeae strains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model of N. gonorrhoeae genital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge with N. gonorrhoeae. Vaginal swabs were quantitatively cultured over 5 days to assess efficacy. RESULTS: PPCM MIC against N. gonorrhoeae ranged between 5-100 µg/mL (agar dilution) and 50-200 µg/mL (microtitre plate method). PPCM/HEC gel applied vaginally prior to bacterial challenge resulted in a concentration-dependent inhibition of infection. Yaso-GEL containing 4% PPCM prevented infection in 100% of mice. Incubation of N. gonorrhoeae with PPCM increased membrane permeability, suggesting PPCM directly compromises N. gonorrhoeae viability, which may be a mechanism by which PPCM inhibits N. gonorrhoeae infection. CONCLUSIONS: Yaso-GEL containing the API PPCM showed significant activity against N. gonorrhoeae in vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to prevent unintended pregnancy and STIs.

Targeted Hyperbranched Nanoparticles for Delivery of Doxorubicin in Breast Cancer Brain Metastasis.

Breast cancer brain metastases (BM) are associated with a dismal prognosis and very limited treatment options. Standard chemotherapy is challenging in BM patients because the high dosage required for an effective outcome causes unacceptable systemic toxicities, a consequence of poor brain penetration, and a short physiological half-life. Nanomedicines have the potential to circumvent off-target toxicities and factors limiting the efficacy of conventional chemotherapy. The HER3 receptor is commonly expressed in breast cancer BM. Here, we investigate the use of hyperbranched polymers (HBP) functionalized with a HER3 bispecific-antibody fragment for cancer cell-specific targeting and pH-responsive release of doxorubicin (DOX) to selectively deliver and treat BM. We demonstrated that DOX-release from the HBP carrier was controlled, gradual, and greater in endosomal acidic conditions (pH 5.5) relative to physiologic pH (pH 7.4). We showed that the HER3-targeted HBP with DOX payload was HER3-specific and induced cytotoxicity in BT474 breast cancer cells (IC50: 17.6 µg/mL). Therapeutic testing in a BM mouse model showed that HER3-targeted HBP with DOX payload impacted tumor proliferation, reduced tumor size, and prolonged overall survival. HER3-targeted HBP level detected in ex vivo brain samples was 14-fold more than untargeted-HBP. The HBP treatments were well tolerated, with less cardiac and oocyte toxicity compared to free DOX. Taken together, our HER3-targeted HBP nanomedicine has the potential to deliver chemotherapy to BM while reducing chemotherapy-associated toxicities.

Emerging drugs for hepatitis D.

INTRODUCTION: Chronic hepatitis delta (CHD) is the most severe form of chronic viral hepatitis. Until recently, its treatment consisted of pegylated interferon alfa (pegIFN) use. AREAS COVERED: Current and new drugs for treating CHD. Virus entry inhibitor bulevirtide has received conditional approval by the European Medicines Agency. Prenylation inhibitor lonafarnib and pegIFN lambda are in phase 3 and nucleic acid polymers in phase 2 of drug development. EXPERT OPINION: Bulevirtide appears to be safe. Its antiviral efficacy increases with treatment duration. Combining bulevirtide with pegIFN has the highest antiviral efficacy short-term. The prenylation inhibitor lonafarnib prevents hepatitis D virus assembly. It is associated with dose-dependent gastrointestinal toxicity and is better used with ritonavir which increases liver lonafarnib concentrations. Lonafarnib also possesses immune modulatory properties which explains some post-treatment beneficial flare cases. Combining lonafarnib/ritonavir with pegIFN has superior antiviral efficacy. Nucleic acid polymers are amphipathic oligonucleotides whose effect appears to be a consequence of phosphorothioate modification of internucleotide linkages. These compounds led to HBsAg clearance in a sizable proportion of patients. PegIFN lambda is associated with less IFN typical side effects. In a phase 2 study it led to 6 months off treatment viral response in one third of patients.

Current Role and Potential of Polymeric Biomaterials in Clinical Obesity Treatment.

The rise of obesity and associated fatal diseases has taken a massive toll worldwide. Despite the existing pharmaceuticals and bariatric surgeries, these approaches manifest limited efficacy or accompany various side effects. Therefore, researchers seek to facilitate the prolonged and specific delivery of therapeutics. Or else, to mimic the essential part of "gastric bypass" by physically blocking excessive absorption via less invasive methods. To achieve these goals, polymeric biomaterials have gained tremendous interest recently. They are known for synthesizing hydrogels, microneedle patches, mucoadhesive coatings, polymer conjugates, and so forth. In this Review, we provide insights into the current studies of polymeric biomaterials in the prevention and treatment of obesity, inspiring future improvements in this regime of study.

Direct Radiolabeling of Trastuzumab-Targeting Triblock Copolymer Vesicles with 89Zr for Positron Emission Tomography Imaging.

Radiolabeled drug nanocarriers that can be easily imaged via positron emission tomography (PET) are highly significant as their in vivo outcome can be quantitatively PET-traced with high sensitivity. However, typical radiolabeling of most PET-guided theranostic vehicles utilizes modification with chelator ligands, which presents various challenges. In addition, unlike passive tumor targeting, specific targeting of drug delivery vehicles via binding affinity to overexpressed cancer cell receptors is crucial to improve the theranostic delivery to tumors. Herein, we developed 89Zr-labeled triblock copolymer polymersomes of 60 nm size through chelator-free radiolabeling. The polymersomes are assembled from poly(N-vinylpyrrolidone)5-b-poly(dimethylsiloxane)30-b-poly(N-vinylpyrrolidone)5 (PVPON5-PDMS30-PVPON5) triblock copolymers followed by adsorption of a degradable tannin, tannic acid (TA), on the polymersome surface through hydrogen bonding. TA serves as an anchoring layer for both 89Zr radionuclide and targeting recombinant humanized monoclonal antibody, trastuzumab (Tmab). Unlike bare PVPON5-PDMS30-PVPON5 polymersomes, TA- and Tmab-modified polymersomes demonstrated a high radiochemical yield of more than 95%. Excellent retention of 89Zr by the vesicle membrane for up to 7 days was confirmed by PET in vivo imaging. Animal biodistribution using healthy BALB/c mice confirmed the clearance of 89Zr-labeled polymersomes through the spleen and liver without their accumulation in bone, unlike the free nonbound 89Zr radiotracer. The 89Zr-radiolabeled polymersomes were found to specifically target BT474 HER2-positive breast cancer cells via the Tmab-TA complex on the vesicle surface. The noncovalent Tmab anchoring to the polymersome membrane can be highly advantageous for nanoparticle modification compared to currently developed covalent methods, as it allows easy and quick integration of a broad range of targeting proteins. Given the ability of these polymersomes to encapsulate and release anticancer therapeutics, they can be further expanded as precision-targeted therapeutic carriers for advancing human health through highly effective drug delivery strategies.

Biomimetic platelet-camouflaged drug-loaded polypyrrole for the precise targeted antithrombotic therapy.

Lower extremity deep venous thrombosis (LEDVT) affects patient's quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of "thrombus thermal ablation and anticoagulation" was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect. Polypyrrole (PPy) and rivaroxban (Riv, an anticoagulant drug) were co-assembled into platelet membrane-coated nanoparticles (NPs), PLT-PPy/Riv NPs, which actively targeted the thrombotic lesion at multiple targets in the platelet membrane and were thermally and drug-specific thrombolysed by 808 nm laser irradiation. The combination therapy resulted in up to 90% thrombolysis in a femoral vein thrombosis model compared to single phototherapy or drug therapy. The results showed that the nanoformulation provided a new direction for remote precise and controlled sustained thrombolysis, which was in line with the trend of nanomedicine towards clinical translation.

Natural ursolic acid based self-therapeutic polymer as nanocarrier to deliver natural resveratrol for natural therapy of acute kidney injury.

Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it's essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI.

Applications of poly(lactic acid) in bone tissue engineering: A review article.

BACKGROUND: Bone tissue engineering is a promising approach to large-scale bone regeneration. This involves the use of an artificial extracellular matrix or scaffold and osteoblasts to promote osteogenesis and ossification at defect sites. Scaffolds are constructed using biomaterials that typically have properties similar to those of natural bone. METHOD: In this study, which is a review of the literature, various evidences have been discussed in the field of Poly Lactic acid (PLA) polymer application and modifications made on it in order to induce osteogenesis and repair bone lesions. RESULTS: PLA is a synthetic aliphatic polymer that has been extensively used for scaffold construction in bone tissue engineering owing to its good processability, biocompatibility, and flexibility in design. However, PLA has some drawbacks, including low osteoconductivity, low cellular adhesion, and the possibility of inflammatory reactions owing to acidic discharge in a living environment. To overcome these issues, a combination of PLA and other biomaterials has been introduced. CONCLUSIONS: This short review discusses PLA's characteristics of PLA, its applications in bone regeneration, and its combination with other biomaterials.