Nur Mita

3D Printing (3DP) has gained decent pace in the past decade in the pharmaceutical and biomedical fields. The approval of 3D-printed medical devices has gained more attraction than that of 3D-printed drug products. However, concerns related to cost-effectiveness, efficacy, and large-scale manufacturing are still prevalent, thus challenging the mainstream development of 3D-printed drug delivery devices. Drug delivery devices and scaffolds, along with the possibilities involving artificial intelligence (AI), machine learning (ML), and automation, for personalized applications. The regulatory guidelines, as well as a glimpse of drug delivery devices under clinical trials, are discussed. Although 3DP offers patient-tailored, on-demand products, its clinical adoption is hindered by regulatory barriers, limited standards, and scalability issues. Integrating AI/ML could offer real-time adaptive clinical manufacturing; however, the guidelines for these disruptive technologies are often unclear. With patient-centric manufacturing, 3D-printed devices and scaffolds could play a key role in personalized medicine, delivering targeted and effective therapies.The transition from proof-of-concept to real-world testing underscores the growing feasibility and clinical relevance of 3DP technologies. With rapid progress in bio-responsive materials and AI-driven design tools, 3D-printed delivery platforms are expected to improve in adaptability and therapeutic effectiveness for next-generation personalized therapies.

Implant failures in orthopedic surgeries can occur due to inflammation, poor osteointegration, and biofilm formation. The local delivery of anti-inflammatory drugs is one of the potential solutions to address orthopedic implant failures caused by extensive inflammation, poor osteointegration, and biofilm formation. This study utilized a simple spray coating technique to deposit multilayer coatings of the anti-inflammatory drug meloxicam and PLGA on 3D printed 316L stainless steel implants. The implants were evaluated for their drug content, drug-polymer miscibility, static contact angle, corrosion resistance, in vitro release, cell adhesion, cell proliferation, and bacterial adhesion studies. The coatings aimed to improve osteointegration and reduce biofilm formation. The drug release studies demonstrated an initial burst release accompanied by sustained release for more than 30 days. The meloxicam-PLGA coated implants showed higher resistance to pitting corrosion, improved adhesion, and proliferation of human U2OS cells in comparison to uncoated implants. In addition, results from cell cytotoxicity studies confirmed that all the coatings are biocompatible and safe for in vivo application. The meloxicam-PLGA coated implants were also found to have significantly lower bacterial adhesion and biofilm formation compared to uncoated implants for both S. aureus ( p < 0.01) and S. pseudintermedius ( p < 0.01). The multilayer coatings developed in this study have the potential to improve adhesion at the implant-bone interface and thus might prevent implant rejections in patients undergoing orthopedic surgery. Moreover, this method can be applied to other drugs and polymers to address the issues related to implant failure, pain management, and surgical site infections. Graphical Abstract

Objective: To investigate the IV pharmacokinetic parameters of clomiphene citrate (CC), a selective estrogen receptor modulator, in mares. Methods: This was an experimental study to assess the pharmacokinetic parameters of CC in the mare. Eight mares received a single 2,000-mg dose of IV CC to identify plasma concentrations over 336 hours. Following this, 6 mares received a multidose regimen of IV CC (2,000 mg, q 24 h) for 5 days to identify trough plasma concentration each day. Results: CC was well tolerated, demonstrated a short elimination half-life of 4.95 ± 1.10 hours and a mean residence time of 7.14 ± 1.59 hours, and reached plasma drug concentrations considered to be therapeutic in women. Peak and trough plasma concentrations were determined. Conclusions: IV CC at 2,000 mg reaches presumed therapeutic concentrations in the mare. Based on the multidose trial, 2,000 mg of IV CC may require administration every 12 to 24 hours. Clinical Relevance: IV CC appears to be well tolerated in the mare. Future fertility trials are warranted to assess the potential that CC may have in increasing the efficiency of equine in vitro embryo production.

Background/Objectives: Personalized 3D-printed (3DP) metallic implants delivery systems are being explored to repair bone fractures, allowing the customization of medical implants that respond to individual patient needs, making it potentially more effective and of greater quality than mass-produced devices. However, challenges associated with postsurgical infections caused by bacterial adhesion remain a clinical issue. To address this, local antibiotic therapies are receiving extensive attention to minimize the risk of implant-related infections. This study investigated the use of amikacin (AMK), a broad-spectrum aminoglycoside antibiotic, incorporated onto 3D-printed 316L stainless steel implants using biodegradable polymer coatings of chitosan and poly lactic-co-glycolic acid (PLGA). Methods: This research examined different approaches to coat 3DP implants with amikacin. Various polymer-based coatings were studied to determine the optimal formulation based on the characteristics and release profile. The optimal formulation was performed on the antibacterial activity studies. Results: AMK-chitosan with PLGA coating implants controlled the rate of drug release for up to one month. The 3DP drug-loaded substrates demonstrated effective, concentration-dependent antibacterial activity against common infective pathogens. AMK-loaded substrates showed antimicrobial effectiveness for one week and inhibited bacteria significantly compared to the uncoated controls. Conclusions: This study demonstrated that 3DP metal surfaces coated with amikacin can provide customizable drug release profiles while effectively inhibiting bacterial growth. These findings highlight the potential of combining 3D printing with localized delivery strategies to prevent implant-associated infections and advance the development of personalized therapies.

Ketotifen fumarate is very effective in treating ocular conditions like allergic conjunctivitis. However, its clinical effectiveness is limited by rapid washout, frequent dosing, and poor bioavailability. This study developed a ketotifen fumarate-loaded in situ forming subconjunctival injectable implant (ISFSI) for use in large animal species such as horses and alpacas. ISFSIs were formulated by dispersing ketotifen fumarate in polylactide-co-glycolide (PLGA) combined with different release retarders (Kolliphor ^® RH 40, Labrasol ^®, and Maisine ^®), then characterized for visual appearance, viscosity, solidification time, and in vitro drug release. The changes in the release medium pH and the solidified ISFSI wet weight were monitored for up to 4 weeks. The selected ISFSI, KFM5, was further characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and rheological behavior. The injectability of KFM5 was predicted using the power law for five different syringe and needle dimensions. Cytotoxicity was tested using the Alamar Blue assay and Calcein AM/PI staining on a human corneal epithelial cell line (HCE-T). Results showed that all ISFSI formulations were clear yellowish, with drug recoveries exceeding 95%, varying viscosities, and solidified upon contact with the release medium. KFM5 exhibited a triphasic drug release profile with the lowest burst release (4.91 ± 0.55%) and followed Higuchi kinetics. SEM imaging revealed a "hollow and sponge-like" structure, while DSC confirmed the crystallinity and thermal transitions of ketotifen fumarate within the solidified implant. Rheological analysis indicated shear-thinning fluid behavior with acceptable injection forces. Cytotoxicity assays confirmed > 90% cell viability, confirming biocompatibility in the ocular tissue. Graphical Abstract

Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for hematological cancers, yet it faces significant hurdles, particularly regarding its efficacy in solid tumors and concerning associated adverse effects. This review provides a comprehensive analysis of the advancements and ongoing challenges in CAR-T therapy. We highlight the transformative potential of nanotechnology in enhancing CAR-T therapy by improving targeting precision, modulating the immune-suppressive tumor microenvironment, and overcoming physical barriers. Nanotechnology facilitates efficient CAR gene delivery into T cells, boosting transfection efficiency and potentially reducing therapy costs. Moreover, nanotechnology offers innovative solutions to mitigate cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cutting-edge nanotechnology platforms for real-time monitoring of CAR-T cell activity and cytokine release are also discussed. By integrating these advancements, we aim to provide valuable insights and pave the way for the next generation of CAR-T cell therapies to overcome current limitations and enhance therapeutic outcomes.

3D Printing (3DP) is an innovative fabrication technology that has gained enormous popularity through its paradigm shifts in manufacturing in several disciplines, including healthcare. In this past decade, we have witnessed the impact of 3DP in drug product development. Almost eight years after the first USFDA approval of the 3D printed tablet Levetiracetam (Spritam), the interest in 3DP for drug products is high. However, regulatory agencies have often questioned its large-scale industrial practicability, and 3DP drug approval/guidelines are yet to be streamlined. In this review, major technologies involved with the fabrication of drug products are introduced along with the prospects of upcoming technologies, including AI (Artificial Intelligence). We have touched upon regulatory updates and discussed the burning limitations, which require immediate focus, illuminating status, and future perspectives on the near future of 3DP in the pharmaceutical field. 3DP offers significant advantages in rapid prototyping for drug products, which could be beneficial for personalizing patient-based pharmaceutical dispensing. It seems inevitable that the coming decades will be marked by exponential growth in personalization, and 3DP could be a paradigm-shifting asset for pharmaceutical professionals.

Despite rapid progress in tissue engineering, the repair and regeneration of bone defects remains challenging, especially for non-homogenous and complicated defects. We have developed and characterized biodegradable drug-eluting scaffolds for bone regeneration utilizing direct powder extrusion-based three-dimensional (3D) printing techniques. The PLGA scaffolds were fabricated using poly (lactic-co-glycolic acid) (PLGA) with inherent viscosities of 0.2 dl/g and 0.4 dl/g and ketoprofen. The effect of parameters such as the infill, geometry, and wall thickness of the drug carrier on the release kinetics of ketoprofen was studied. The release studies revealed that infill density significantly impacts the release performance, where 10% infill showed faster and almost complete release of the drug, whereas 50% infill demonstrated a sustained release. The Korsmeyer–Peppas model showed the best fit for release data irrespective of the PLGA molecular weight and infill density. It was demonstrated that printing parameters such as infill density, scaffold wall thickness, and geometry played an important role in controlling the release and, therefore, in designing customized drug-eluting scaffolds for bone regeneration.

Meloxicam, a selective COX-2 inhibitor, has demonstrated clinical effectiveness in managing inflammation and acute pain. Although available in oral and parenteral formulations such as capsule, tablet, suspension, and solution, frequent administration is necessary to maintain therapeutic efficacy, which can increase adverse effects and patient non-compliance. To address these issues, several sustained drug delivery strategies such as oral, transdermal, transmucosal, injectable, and implantable drug delivery systems have been developed for meloxicam. These sustained drug delivery strategies have the potential to improve the therapeutic efficacy and safety profile of meloxicam, thereby reducing the frequency of dosing and associated gastrointestinal side effects. The choice of drug delivery system will depend on the desired release profile, the target site of inflammation, and the mode of administration. Overall, meloxicam sustained delivery systems offer better patient compliance, and reduce the side effects, thereby improving the clinical applications of this drug. Herein, we discuss in detail different strategies for sustained delivery of meloxicam.