Polymer-based drug-eluting stent treatment extends the time to reintervention for patients with symptomatic femoropopliteal artery disease: clinical evidence and potential economic value.

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were performed through 5 years. Mean time to first reintervention was calculated in post-hoc analysis for patients who underwent a clinically driven target lesion revascularization (CD-TLR) through 3 or 5 years following the index procedure. To simulate potential cost savings associated with differential CD-TLR burden over time, a cost-avoidance analysis using input parameters from IMPERIAL and US 100% Medicare standard analytical files was developed. Results: Among patients with a first CD-TLR through 3 years of follow-up, mean time to reintervention was 5.5 months longer (difference 166 days, 95% CI: 51, 282 days; p = 0.0058) for patients treated with Eluvia (n = 56) than for those treated with Zilver PTX (n = 30). Through the 5-year study follow-up period, CD-TLR rates were 29.3% (68/232) for Eluvia and 34.2% (39/114) for Zilver PTX (p = 0.3540) and mean time to first reintervention exceeded 2 years for patients treated with Eluvia at 737 days versus 645 days for the Zilver PTX group (difference 92 days, 95% CI: -85, 269 days; p = 0.3099). Simulated savings considering reinterventions occurring over 1 and 5 years following initial use of Eluvia over Zilver PTX were US $1,395,635 and US $1,531,795, respectively, when IMPERIAL CD-TLR rates were extrapolated to 1000 patients. Conclusion: IMPERIAL data suggest initial treatment with Eluvia extends the time patients spend without undergoing reintervention. This extension may be associated with cost savings in relevant time frames.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases.

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Antiangiogenic Therapeutic mRNA Delivery Using Lung-Selective Polymeric Nanomedicine for Lung Cancer Treatment.

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.

Application of PLLA (Poly-L-Lactic acid) for rejuvenation and reproduction of facial cutaneous tissue in aesthetics: A review.

Poly-L-lactin acid (PLLA) has been widely used in the field of bio-medicine. In 2004, as an injectable material, PLLA was approved by the FDA to treat AIDS-related facial atrophy. Since then, several injectable stuffs containing PLLA have been approved for marketing in various countries and regions. Recently, PLLA has often been used to treat facial rejuvenation problems like cutaneous depressions and static wrinkles which always induce unsatisfactory facial expression. This review introduces the physicochemical properties, regeneration stimulating mechanism, applications in aesthetics and injectable comorbidity of PLLA.

Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared photoactivatable ferroptosis-immunotherapy.

Enzymes provide a class of potential options to treat cancer, while the precise regulation of enzyme activities for effective and safe therapeutic actions has been poorly reported. Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared (NIR-II) photoactivatable ferroptosis-immunotherapy are reported in this study. Such nanoagents (termed SPHGA) consist of hemoglobin (Hb)-based semiconducting polymer (SP@Hb), adenosine deaminase (ADA) and glucose oxidase (GOx) with loadings in a thermal-responsive nanoparticle shell. NIR-II photoactivation of SPHGA results in the generation of heat to trigger on-demand releases of two enzymes (ADA and GOx) via destroying the thermal-responsive nanoparticle shells. In the tumor microenvironment, GOx oxidizes glucose to form hydrogen peroxide (H2O2), which promotes the Fenton reaction of iron in SP@Hb, resulting in an enhanced ferroptosis effect and immunogenic cell death (ICD). In addition, ADA degrades high-level adenosine to reverse the immunosuppressive microenvironment, thus amplifying antitumor immune responses. Via NIR-II photoactivatable ferroptosis-immunotherapy, SPHGA shows an improved effect to absolutely remove bilateral tumors and effectively suppress tumor metastases in subcutaneous 4T1 breast cancer models. This study presents a dual-enzyme-based nanoagent with controllable therapeutic actions for effective and precise cancer therapy.

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.

A review of hyaluronic acid-based therapeutics for the treatment and management of arthritis.

Hyaluronic acid (HA), a biodegradable, biocompatible and non-immunogenic therapeutic polymer is a key component of the cartilage extracellular matrix (ECM) and has been widely used to manage two major types of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA). OA joints are characterized by lower concentrations of depolymerized (low molecular weight) HA, resulting in reduced physiological viscoelasticity, while in RA, the associated immune cells are over-expressed with various cell surface receptors such as CD44. Due to HA's inherent viscoelastic property and its ability to target CD44, there has been a surge of interest in developing HA-based systems to deliver various bioactives (drugs and biologics) and manage arthritis. Considering therapeutic benefits of HA in arthritis management and potential advantages of novel delivery systems, bioactive delivery through HA-based systems is beginning to display improved outcomes over bioactive only treatment. The benefits include enhanced bioactive uptake due to receptor-mediated targeting, prolonged retention of bioactives in the synovium, reduced expressions of proinflammatory mediators, enhanced cartilage regeneration, reduced drug toxicity due to sustained release, and improved and cost-effective treatment. This review provides an underlying rationale to prepare and use HA-based bioactive delivery systems for arthritis applications. With special emphasis given to preclinical/clinical results, this article reviews various bioactive-loaded HA-based particulate carriers (organic and inorganic), gels, scaffolds and polymer-drug conjugates that have been reported to treat and manage OA and RA. Furthermore, the review identifies several key challenges and provides valuable suggestions to address them. Various developments, strategies and suggestions described in this review may guide the formulation scientists to optimize HA-based bioactive delivery systems as an effective approach to manage and treat arthritis effectively.

Photocleavable Visible Light-Triggered Anthraquinone-Derived Water-Soluble Block Copolymer for Peroxynitrite Generation in Cancer Therapy.

We report a facile stimuli-responsive strategy to generate reactive oxygen and nitrogen species (ROS and RNS) in the biological milieu from a photocleavable water-soluble block copolymer under visible light irradiation (427 nm, 2.25 mW/cm2). An anthraquinone-based water-soluble polymeric nitric oxide (NO) donor (BCPx-NO) is synthesized, which exhibits NO release in the range of 40-65 µM within 10 h of photoirradiation with a half-life of 30-103 min. Additionally, BCPx-NO produces peroxynitrite (ONOO-) and singlet oxygen (1O2) under photoirradiation. To understand the mechanism of NO release and photolysis of the functional group under blue light, we prepared a small-molecule anthraquinone-based N-nitrosamine (NOD). The cellular investigation of the effect of spatiotemporally controlled ONOO- and 1O2 generation from the NO donor polymeric nanoparticles in a triple negative breast adenocarcinoma (MDA-MB-231) under visible light irradiation (white light, 5.83 mW/cm2; total dose 31.5 J/cm2) showed an IC50 of 0.6 mg/mL. The stimuli-responsive strategy using a photolabile water-soluble block copolymer employed to generate ROS and RNS in a biological setting widens the horizon for their potential in cancer therapy.

An in vivo duck hepatitis B virus model recapitulates key aspects of nucleic acid polymer treatment outcomes in chronic hepatitis B patients.

Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing. Here we report on an optimized in vivo DHBV duck model and explore several characteristics of NAP treatment. REP2139 was efficacious in reducing DHBV DNA and DHBsAg levels in approximately half of the treated ducks, whether administered intraperitoneally or subcutaneously. Intrahepatic or serum NAP concentrations did not correlate with efficacy, nor did the appearance of anti-DHBsAg antibodies. Furthermore, NAP efficacy was only observed in experimentally infected ducks, not in endogenously infected ducks (vertical transmission). REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy. Destabilized REP2165 showed a different activity profile with a more homogenous antiviral response followed by a faster rebound. In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders.

Berdazimer Topical Gel, 10.3%: First Approval.

Berdazimer topical gel, 10.3% (ZELSUVMI™) is a nitric oxide (NO) releasing topical gel developed by Novan Inc. (a Ligand Pharmaceuticals company) for the treatment of molluscum contagiosum (MC). Novan has used their proprietary NO-based technology platform (NITRICIL™), which stores gaseous NO species on large polymers, in the development of berdazimer topical gel, 10.3%. In January 2024, berdazimer topical gel, 10.3% was approved for the topical treatment of MC in adult and paediatric patients 1 year of age and older in the USA. This article summarizes the milestones in the development of berdazimer topical gel, 10.3% leading to this first approval for the treatment of MC.

Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy.

Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.

A biodegradable semiconducting polymer phototherapeutic agent for safe cancer phototherapy.

Combined photodynamic therapy (PDT) and photothermal therapy (PTT) not only effectively reduce the hypoxic resistance to PDT, but also overcome the heat shock effect to PTT. However, the residual phototherapeutic agents still produce reactive oxygen species (ROS) to damage normal tissue under sunlight after treatment, which induces undesirable side effects to limit their biomedical application. Herein, a facile strategy is proposed to construct a biodegradable semiconducting polymer p-DTT, which is constructed by thieno[3,2-b]thiophene modified diketopyrrolopyrrole and (E)-1,2-bis(5-(trimethylstannyl)thiophen-2-yl)ethene moieties, to avoid the post-treatment side effects of phototherapy. Additionally, p-DTT exhibits strong photoacoustic (PA) for imaging, as well as good ROS production capacity and high photothermal conversion efficiency for synergistic PDT and PTT, which has been confirmed by both in vitro and in vivo results. After phototherapy, p-DTT could be gradually oxidized and degraded by endogenous ClO-, and subsequently lose ROS production and photothermal conversion capacities, which can guarantee the post-treatment safety, and address above key limitation of traditional phototherapy.

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.

Metallopolymer strategy to explore hypoxic active narrow-bandgap photosensitizers for effective cancer photodynamic therapy.

Practical photodynamic therapy calls for high-performance, less O2-dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based photosensitizers exhibit excellent photocatalytic performance, but the in vivo applications are hindered by conventional O2-dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy for engineering iridium complexes exhibiting Type-I photochemistry and enhancing absorption intensity in the blue to near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1, where the iridium atom is covalently coupled to the polymer backbone, is over 80 times higher than that of its mother polymer without iridium under 680 nm irradiation. This strategy also works effectively when the iridium atom is directly included (Ir-P2) in the polymer backbones, exhibiting wide generality. The metallopolymer nanoparticles exhibiting efficient O2•- generation are conjugated with integrin αvß3 binding cRGD to achieve targeted photodynamic therapy.

Emerging natural polymer-based architectured nanotherapeutics for the treatment of cancer.

The field of cancer therapy is advancing rapidly, placing a crucial emphasis on innovative drug delivery systems. The increasing global impact of cancer highlights the need for creative therapeutic strategies. Natural polymer-based nanotherapeutics have emerged as a captivating avenue in this pursuit, drawing substantial attention due to their inherent attributes. These attributes include biodegradability, biocompatibility, negligible toxicity, extended circulation time, and a wide range of therapeutic payloads. The unique size, shape, and morphological characteristics of these systems facilitate profound tissue penetration, complementing active and passive targeting strategies. Moreover, these nanotherapeutics exploit specific cellular and subcellular trafficking pathways, providing precise control over drug release kinetics. This comprehensive review emphasizes the utilization of naturally occurring polymers such as polysaccharides (e.g., chitosan, hyaluronic acid, alginates, dextran, and cyclodextrin) and protein-based polymers (e.g., ferritin, gelatin, albumin) as the foundation for nanoparticle development. The paper meticulously examines their in vitro characteristics alongside in vivo efficacy, particularly focusing on their pivotal role in ameliorating diverse types of solid tumors within cancer therapy. The amalgamation of material science ingenuity and biological insight has led to the formulation of these nanoparticles, showcasing their potential to reshape the landscape of cancer treatment.

Engineered praseodymium sulfide nanocarrier and supramolecular association of anticancer drug for effective delivery to breast cancer cells.

Metal sulfide nanoparticles are synthesized for their biomedical applications, including cancer drug targeting. This paper reports a novel nanocomposite made of praseodymium sulfide nanoparticles and poly-cyclodextrin. The praseodymium sulfide nanoparticles were synthesized hydrothermal, autoclaving the nitrate precursors at 150 °C for 18 hours. The material is characterized using XRD and shows an orthorhombic crystal system with high crystallinity. The size and morphology of the nanomaterial were optimized. The material shows a rod-shaped morphology, as seen in the TEM image, with 150 ± 3 nm length and 25 ± 5 nm width. Particle size analysis supports this size range. The colloidal particles were stable in the aqueous medium without precipitation at neutral pH. The elements in the material in the polymer-coated form and their electronic states are studied by X-ray photoelectron spectroscopy. Thermogravimetry confirms that the material contains about 18.5% of the weight of the polymer. The material has an observable magnetic property at room temperature due to the praseodymium element. The UV-vis-NIR absorption spectrum of the material shows a long absorption range that extends to 1200 nm. The drug 5-fluorouracil is encapsulated in the nanoparticles through host: guest association, and its release profile is analyzed. The release is modulated at a slightly acidic pH, indicating the pH-tunability. The nanoparticles and 5-fluorouracil were taken in the w/w ratio of 2:1 (2/1 mg in 1 mL of deionized water). Further, the in vitro anticancer activity of the drug-encapsulated material is screened on breast cancer and non-cancerous cell lines. The IC50 values are reported, and the advantageous properties of the material as drug carriers are discussed.

Localized Photodynamic Therapy Using a Chlorin e6-Embedded Silicone-Covered Self-Expandable Metallic Stent as a Palliative Treatment for Malignant Esophageal Strictures.

Localized photodynamic therapy (PDT) uses a polymeric-photosensitizer (PS)-embedded, covered self-expandable metallic stent (SEMS). PDT is minimally invasive and a noteworthy potential alternative for treating esophageal strictures, where surgery is not a viable option. However, preclinical evidence is insufficient, and optimized irradiation energy dose ranges for localized PDT are unclear. Herein, we validated the irradiation energy doses of the SEMS (embedded in a PS using chlorin e6 [Ce6] and covered in silicone) and PDT-induced tissue changes in a rat esophagus. Cytotoxicity and phototoxicity in the Ce6-embedded SEMS piece with laser irradiation were significantly higher than that of the silicone-covered SEMS with or without laser and the Ce6-embedded silicone-covered SEMS without laser groups (all p < 0.001). Moreover, surface morphology, atomic changes, and homogeneous coverage of the Ce6-embedded silicone-covered membrane were confirmed. The ablation range of the porcine liver was proportionally increased with the irradiation dose (all p < 0.001). The ablation region was identified at different irradiation energy doses of 50, 100, 200, and 400 J/cm2. The in vivo study in the rat esophagus comprised a control group and 100, 200, and 400 J/cm2 energy-dose groups. Finally, histology and immunohistochemistry (TUNEL and Ki67) confirmed that the optimized Ce6-embedded silicone-covered SEMS with selected irradiation energy doses (200 and 400 J/cm2) effectively damaged the esophageal tissue without ductal perforation. The polymeric PS-embedded silicone-covered SEMS can be easily placed via a minimally invasive approach and represents a promising new approach for the palliative treatment of malignant esophageal strictures.

Aerosolizable Pyrazinamide-Loaded Biodegradable Nanoparticles for the Management of Pulmonary Tuberculosis.

Background: Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. Methods: In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. Results: Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of -17.23 mV, and in vitro drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, in vitro drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 µm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in in vivo deposition with respect to pure drug deposition, respectively. In vitro drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. Conclusion: PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability.

Resolving acne with optimized adapalene microspongeal gel, in vivo and clinical evaluations.

In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 33. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.

A paradigm use of monoclonal antibodies-conjugated nanoparticles in breast cancer treatment: current status and potential approaches.

Monoclonal antibodies (mAbs) are integral to cancer treatment over conventional non-specific therapy methods. This study provides a scoping review of the clinically approved mAbs, focusing on the current application of different nanocarrier technologies as drug delivery targets for mAb-conjugated nanoparticles (NPs) as potential features for breast cancer (BC) treatment. An extensive literature search was conducted between the years 2000 and 2023 using various sources of databases. The first part covered mAb classification, types, and mechanisms of action, pharmacokinetics and clinical applications in BC. The second part covered polymeric, lipid and inorganic-based NPs, which are a variety of mAb-conjugated NPs targeting BC. A total of 20 relevant studies were enrolled indicating there are three different types of nanoparticular systems (polymeric NPs, inorganic NPs and lipid-based NPs) that can be used for BC treatment by being loaded with various active substances and conjugated with these antibodies. While mAbs have altered the way in cancer treatment due to targeting cancer cells specifically, the delivery of mAbs with nanoparticulate systems is important in the treatment of BC, as NPs are still being investigated as distinctive and promising drug delivery methods that can be employed for effective treatment of BC.