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Glioblastoma multiforme (GBM) is a widespread and life-threatening kind of brain cancer, which has a high mortality rate. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, irreversibly adheres to a conserved cysteine residue of two enzymes BTK and BMX, inhibiting their kinase activities, which leads to suppression of the growth of glioma cells. This study synthesised PLGA-PEG-folate (PPF) polymer and subsequently encapsulated ibrutinib within PPF nanoparticles (IBT-PPF-NPs). H NMR spectra confirmed the synthesis of PPF polymer. The efficiency of IBT-PPF-NPs was 97 ± 2.26% with 8.8 ± 0.2% drug loading. The particle size was 208 ± 4.8 nm. The IC 50 value of free ibrutinib, IB-PPF-NPs and ibrutinib encapsulated in PLGA NPs (IB-P-NPs) was 10.2, 7.6 and 10.13 µM in C6 cell lines, whereas in U-87 MG cells was 24.4, 16 and 25.2 µM, respectively. The cellular uptake of FITC-PPF-NPs increased from 47.6% to 90.3% in C6 cells and from 55% to 97.3% in U-87 MG cells compared to FITC-P-NPs. The in vivo results indicate a significant reduction in tumour size in treatment groups in comparison to control groups, while the group that received the intratumoural injection of IB-PPF-NPs exhibited a greater reduction. The folate-targeting agent enhances the nanoparticles' effectiveness by promoting their uptake through the endocytosis pathway.

Polymeric drug delivery systems (PDDS) play a crucial role in controlled drug release, providing improved therapeutic outcomes. However, formulating PDDS and predicting their release profiles remain challenging due to their complex structures and the numerous variables that influence their behavior. Traditional mathematical and empirical prediction methods are limited in capturing these complexities. Recent studies have unveiled the potential of Machine Learning (ML) in revolutionizing drug delivery, particularly in formulating complex PDDS. This article provides an overview of the significant and fundamental principles of various ML in estimating PDDS drug release behavior. Our focus extends to the accomplishments and pivotal discoveries in current research, spanning seven distinct sustained-release drug delivery systems: matrix tablets, microspheres, implants, hydrogels, films, 3D-printed dosage forms, and other innovations. Furthermore, it addresses the challenges associated with ML-based drug release prediction and presents current solutions while delving into future perspectives. Our investigation underscores the significance of Artificial Neural Networks in ML-based PDDS release profile prediction, surpassing both traditional and alternative ML-based methods. These extensive datasets can be drawn from literature-based resources or enhanced through specific algorithms. Moreover, ensemble-based models have proven advantageous in scenarios involving intricate relationships, such as a high number of output parameters. ML-based drug release prediction notably exhibits substantial promise in 3D-printed dosage forms, presenting a frontier for personalized medicine and precise drug delivery., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hypertrophic scars are defined as visible lesions formed by excessive wound healing that cause cosmetic and, in some cases, functional challenges in patients. This study aimed to assess the efficacy of intralesional injections of losartan-loaded in situ forming gel and compare it with the common treatment (triamcinolone) in preventing scar formation. The formulation was prepared using a thermosensitive PLGA-PEG-PLGA triblock copolymer. Ear scar tissue in rabbits represented the hypertrophic scar, and the animals were treated with three treatments in three groups. Nine weeks following the single treatment, images of the scars were obtained and quantitatively analyzed using ImageJ and light microscopy was used to evaluate the fibroblast cell number, vascularization, inflammation and collagen deposition and fibrosis in H&E-stained sample tissue. According to the results based on the ImageJ and the Vancouver criteria, the losartan in situ forming gel (F-LG) indicated significantly higher improving effects on decreased vascularity and pigmentation in comparison with triamcinolone (F-TA) and placebo as a control (F-Ctl), although the effect F-LG was almost similar to F-TA on pliability and scar height, and they were better than the control. Histological findings showed F-LG and F-TA have less inflammatory and fibroblast cells compared to F-Ctl. Also, results indicated the dermal layers of the F-TA and F-LG groups' scar were thinner, and the deposition of collagens was reduced compared to the control. Consequently, F-LG was found to be an effective treatment in reducing scarring and promoting wound healing.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest to disclose. Ethical Approval: All protocols were approved by the Institutional Animal Care and Ethical Committee of the Iran University of Medical Sciences (IR.IUMS.FMD.REC.1399.004). Informed Consent: For this type of study, informed consent is not required., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The global incidence of melanoma, the most lethal form of skin cancer, continues to escalate, emphasizing the urgent need for more effective therapeutic strategies. This review assesses the latest advancements in topical and transdermal drug delivery systems, positioning them as promising alternatives. These systems allow for the direct application of therapeutic agents to tumor sites, enhancing drug effectiveness, improving patient compliance, and reducing systemic toxicity. Specifically, innovations such as nanoparticles, microneedles, and vesicular systems are explored for their potential to optimize topical and localized drug delivery. By incorporating a graphical overview of these drug delivery vehicles, we visually underscore their roles in enhancing therapeutic outcomes across various treatment categories such as chemotherapy, immunotherapy, phototherapy, phytotherapy, and targeted therapy. This article critically evaluates recent breakthroughs, addresses the current challenges faced by researchers, and explores the future directions of topical and transdermal approaches in melanoma management. By presenting a summary of the latest research and predicting future trends, this review aims to inform ongoing developments and encourage further innovation in strategies for treating melanoma., Competing Interests: Declarations. Ethics approval and consent to participate: This article does not contain any studies with human participants or animals performed by any of the authors. Consent for publication: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. Controlled Release Society.)

Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123 nm with zeta potential around - 25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite advances in bone tissue engineering, fabricating a scaffold which can be used as an implant for large bone defects remains challenge. One of the great importance in fabricating a biomimetic bone implant is considering the possibility of the integration of the structure and function of implants with hierarchical structure of bone. Herein, we propose a method to mimic the structural unit of compact bone, osteon, with spatial pattern of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) in the adjacent layers that mimic Haversian canal and lamella, respectively. To this end, coaxial extrusion-based bioprinting technique via a customized quadruple-layer core-shell nozzle was employed. 3D implant scaffold-cell construct was fabricated by using polyethylene glycol as a hollowing agent in the first layer, gelatin methacryloyl (GelMA) and alginate blended hydrogel encapsulating HUVEC cells with vascular endothelial growth factor nanoparticles in the second layer (vasculogenic layer) to mimic vascular vessel, and GelMA and alginate blended hydrogel containing hMSCs cells in the outer osteogenic layer to imitate lamella. Two types of bone minerals, whitlockite and hydroxyapatite, were incorporated in osteogenic layer to induce osteoblastic differentiation and enhance mechanical properties (the young's modules of nanocomposite increased from 35 kPa to 80 kPa). In-vitro evaluations demonstrated high cell viability (94 % within 10 days) and proliferation. Furthermore, ALP enzyme activity increased considerably within 2 weeks and mineralized extra cellular matrix considerably produced within 3 weeks. Also, a significant increase in osteogenic markers was observed indicating the presence of differentiated osteoblast cells. Therefore, the work indicates the potential of single step 3D bioprinting process to fabricate biomimetic osteons to use as bone grafts for regeneration., Competing Interests: Conflicts of interest Hae Lin Jang is a founder and owns equity in Curer Inc., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Recently biodegradable nanoparticles are the center of attention for the development of drug delivery systems. Molecularly imprinted polymer (MIP) is an interesting candidate for designing drug nano-carriers. MIP-based nanoparticles could be used for cancer treatment and exhibited the potential to fill gaps regarding to ligand-based nanomaterials. Also, the presence of a cross-linker can play an essential role in nanoparticle stability and physicochemical properties of nanoparticles after synthesis., Objectives: In this research, a biodegradable drug delivery system based on MIP nanoparticles was prepared using a biodegradable cross-linker (dimethacryloyl hydroxylamine, DMHA) for methotrexate (MTX). A hydrolysable functional group CO-O-NH-CO was added to the crosslinking agent to increase the final biodegradability of the polymer., Methods: Firstly, a biodegradable cross-linker was synthesized. Then, the non-imprinted polymers were prepared through mini-emulsion polymerization in the absence of a template; and efficient particle size distribution was determined. Finally, methotrexate was placed in imprinted polymers to achieve the desired MIP. Different types of MIPs were synthesized using different molar ratios of template, cross-linker, and functional monomer, and the optimal molar ratio was obtained at 1:4:20, respectively., Results: HNMR successfully confirmed the chemical structure of the cross-linker. According to SEM images, nanoparticles had a spherical shape with a smooth surface. The imprinted nanoparticles showed a narrow size distribution with an average of 120 nm at a high ratio of cross-linker. The drug loading and entrapment efficiency were 6.4% and 92%, respectively. The biodegradability studies indicated that the nanoparticles prepared by DMHA had a more degradability rate than ethylene glycol dimethacrylate as a conventional cross-linker. Also, the polymer degradation rate was higher in alkaline environments. Release studies in physiological and alkaline buffer showed an initial burst release of a quarter of loaded MTX during the day and a 70% release during a week. The Korsmeyer-Peppas model described the release pattern. The cytotoxicity of MTX loaded in nanoparticles was studied on the MCF-7 cell line, and the IC 50 was 3.54 μg/ml., Conclusion: It was demonstrated that nanoparticles prepared by DMHA have the potential to be used as biodegradable drug carriers for anticancer delivery. Synthesis schema of molecular imprinting of methotrexate in biodegradable polymer based on dimethacryloyl hydroxylamine cross-linker, for use as nanocarrier anticancer delivery to breast tumor., (© 2022. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

Although stem cell therapy is a major area of interest in tissue engineering, providing proper oxygen tension, good viability, and cell differentiation remain challenges in tissue-engineered scaffolds. In this study, an osteogenic scaffold was fabricated using the 3D bio-printing technique. The bio-ink contained alginate hydrogel, encapsulated human bone marrow-derived mesenchymal stem cells (hBM-MSCs), calcium peroxide nanoparticles (CPO NPs) as an oxygen generating biomaterial, and bone morphogenic protein-2 nanoparticles (BMP2 NPs) as an osteoinductive growth factor. CPO NPs were synthesized with the hydrolysis-precipitation method, and their concentrations in the bio-ink were optimized. Scaffolds containing CPO 3% (w/w) were preferred, because they generated sufficient oxygen gas for 20 days, increased mechanical strength after 20 days, and had sufficient stability. The CPO NPs effect on the viability of embedded hBM-MSCs under hypoxic conditions was analyzed. Live/Dead staining results represented a 22% improvement in CPO 3% scaffold viability on day 7. Therefore, CPO NPs constituted a promising survival factor. BMP2 NPs were prepared with the double emulsification technique. The incorporation of both BMP2 and CPO NPs resulted in the upregulation of Runt-related transcription factor 2, Collagen type I alpha 1, and the osteocalcin genes compared to internal references in osteogenic media. Overall, the proposed 3D bio-printed osteogenic scaffold in this study has moved scientific research one step forward toward successful stem cell therapy and helped improve host tissue healing by biological activity enhancement, especially for low oxygen pressure tissues., (Copyright © 2022 Elsevier B.V. All rights reserved.)