Drug Retention Research Articles

Obesity in rheumatoid arthritis: impact on response to biologic therapies

Background: We performed a service evaluation of local patients with rheumatoid arthritis (RA) treated with biologic or targeted systemic disease-modifying anti-rheumatic drug (b/ts)DMARDs to see if patients who were obese had different outcomes, and whether referral to specialist obesity services was considered. In addition, we undertook a systematic review of the impact of obesity on treatment outcomes in patients with RA receiving biologics. Methods: A retrospective case note review was performed for 220 patients with RA attending clinic on treatment with a (b/ts)DMARD. BMI, DAS28, DAS components and demographics were recorded. Referrals to weight management services were evaluated. A systematic review was performed according to PRISMA guidelines (PROSPERO CRD42023433669). Electronic databases were searched for papers reporting RA patients receiving biologics with clinical responses in patients with and without obesity. Results: Within our service, 24% of patients were obese; 12% were morbidly obese. Patients with obesity had higher disease activity scores. Only 25% of eligible patients were referred to weight management services. 238 records were identified through database searches. 69 full-text records were assessed for eligibility and data extracted from 39 records including 40,445 patients receiving a variety of biologic agents. Reduced responses, remission rates, and drug retention were seen in patients with obesity receiving TNF inhibitors (TNFi), but this was not seen for abatacept, rituximab, or tocilizumab. Discussion: Obesity is common in patients with RA and can be associated with higher disease activity. Patients who are obese are less likely to reach remission with TNFi. The use of non-TNFi biologics should be considered earlier in the treatment pathway alongside holistic approaches to aid lifestyle change for this patient group.

Transdermal gene delivery

Gene delivery has revolutionized conventional medical approaches to vaccination, cancer, and autoimmune diseases. However, current gene delivery methods are limited to either intravenous administration or direct local injections, failing to achieve well biosafety, tissue targeting, drug retention, and transfection efficiency for desired therapeutic outcomes. Transdermal drug delivery based on various delivery strategies can offer improved therapeutic potential and superior patient experiences. Recently, there has been increased foundational and clinical research focusing on the role of the transdermal route in gene delivery and exploring its impact on the efficiency of gene delivery. This review introduces the recent advances in transdermal gene delivery approaches facilitated by drug formulations and medical devices, as well as discusses their prospects.

Molecular detection of rifampicin-resistant Mycobacterium tuberculosis by polymerase chain reaction in Ethiopia: a systematic review and meta-analysis.

Tuberculosis is a contagious bacterial disease caused by Mycobacterium tuberculosis. The emergence and spread of drug-resistant strains of M. tuberculosis in both developing and developed countries has made diagnosis, treatment, and control of tuberculosis more difficult. The PCR assay, which is a fast and sensitive technique and an alternative method for detecting multidrug-resistant tuberculosis, is used to determine rifampicin (RIF) resistance. There is no single figure in Ethiopia that represents rifampicin-resistant tuberculosis and that is why this study was conducted to overcome the inconsistency of the results of the previous studies. Studies were researched from five major electronic databases. Studies which were cross-sectional in design, published, and written in English were included. The data were extracted using Microsoft Excel, and the data were managed and analyzed using Stata™ Version 17.0 statistical software. The Forest plot was used to check the presence of heterogeneity. The publication bias, meta-regression, and subgroup analysis were used to find out the source of heterogeneity. A random effect analysis model was used to pool the prevalence of RR TB from primary studies, and associated factors of RR among TB patients were identified using Meta regression. The presence of association was reported using OR with 95% CI. The overall pooled prevalence of tuberculosis was 14.9% (95% CI: 13.34, 16.46), of these approximately 7.48% (95% CI: 6.30, 8.66) showed rifampicin-resistant tuberculosis in Ethiopia. Among the computed variables, 2.05% living with HIV1.39 (95%CI: 1.13, 1.72) and having a history of TB treatment (95%CI: 1.34, 3.15) were identified as significant factors associated with RR TB in Ethiopia. Drug-resistant TB is one of the prevalent emerging infectious diseases among TB patients, which affects approximately one out of every thirteen TB patients. Having TB-HIV coinfection and a history of prior TB treatment were identified as significant factors associated with RR TB. To prevent and control RR TB, patients should complete their follow-up course; the health professionals should educate the actions taken by the patients when they experience drug toxicity and side effects; and the Minister of Health should initiate telemedicine and recruit tracers to overcome TB patients' default and have good drug adherence and retention after initiation of the treatment.

Quercetin nanocrystals for bioavailability enhancement: impact of different functional stabilizers on in vitro/in vivo drug performances

The purpose of this study was to investigate the impact of different functional stabilizers on in vitro/in vivo drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution in vitro, and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant differences in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC0∼ t of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the C max showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with T max at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same T max at 5.33 h. The longest MRT0∼ t (11.72 h) and t 1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution in vitro and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution in vitro, oral absorption and drug retention in vivo by changing the type of functional stabilizers in NCs preparation.

Combination of anti-inflammatory therapy and RNA interference by light-inducible hybrid nanomedicine for osteoarthritis treatment

Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly(β-amino-ester)-coated gold nanocages (AuNCs), which is further incorporated with the phase-change material (lauric acid/stearic acid, LA/SA). Following intra-articular (IA) injection in vivo, the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models. The photothermal effect, induced by AuNCs, not only promotes DIA and siRNA release, but also upregulates the expression of heat shock protein 70 (HSP-70) to resist the apoptosis of chondrocytes in the inflammatory condition. The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects, which greatly contribute to the joint repair of OA mice. This study offers a promising combination strategy for OA treatment.

Lipid-based microemulsion gel for the topical delivery of methotrexate: an optimized, rheologically acceptable formulation with conducive dermatokinetics.

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.

A Complete Sojourn of Current Trends in Gastro-retentive Drug Delivery System: Recent Advances and Patent Survey.

The current work aims to provide a complete sojourn on gastro-retentive drug delivery system (GRDDS) along with formulation methods, polymer selection, and in vitro/ in vivo challenges with finished dosage forms. Ideally, a biopharmaceutical-hindered drug has a rapid clearance and erratic bioavailability due to its low aqueous solubility and permeability. Additionally, it also suffers from high first-pass metabolism and pre-systemic gut wall clearance. Gastro-retentive drug delivery systems have become an emerging technology where newer methodologies and scientific approaches have been used to provide the controlled release of drugs and provide a protective mechanism in the stomach. By the virtue of utilizing GRDDS as a dosage form, these formulations increase Gastroretention time (GRT) which prolongs the controlled release of the drug in the dosage form. GRDDS contribute to increased drug bioavailability and targeting at a site of action, which enhances therapeutic action and offers significant patient compliance. Furthermore, the present work also highlighted the critical role of polymers in favoring drug retention across GIT with the mechanism of gastro-retention and recommended concentration ranges. The emerging technology is also highlighted by the approved drug products and patented formulations in the recent decade which is depicted in a justified manner. GRDDS formulations have demonstrated clinical efficacy, which is supported by a compilation of patents for cutting-edge innovations in dosage forms that can be held in the stomach for an extended period of time.

Stable Dietary Ora-Curcumin Formulation Protects from Experimental Colitis and Colorectal Cancer.

Inflammatory bowel disease (IBD) is a chronic gut disorder that also elevates the risk of colorectal cancer (CRC). The global incidence and severity of IBD are rising, yet existing therapies often lead to severe side effects. Curcumin offers potent anti-inflammatory and chemotherapeutic properties. However, its clinical translation is hindered by rapid metabolism, as well as poor water solubility and stability, which limits its bioavailability. To address these challenges, we developed OC-S, a water-soluble and colon-targeted curcumin formulation that protects against colitis in mice. The current study advances OC-S as a dietary supplement by establishing its stability and compatibility with various commercial dietary products. Further, OC-S exhibited specific binding to inflamed colon tissue, potentially aiding in targeted drug retention at the inflammation site in colitis with diarrhea symptoms. We further investigated its efficacy in vivo and in vitro using a murine model of colitis and tumoroids from APCmin mice. OC-S significantly reduced colitis severity and pro-inflammatory cytokine expression compared with curcumin, even at very low doses (5 mg/kg/day). It also demonstrated higher anti-proliferative activity in CRC cells and colon cancer tumoroids vs. curcumin. Overall, this study demonstrated that OC-S effectively targets and retains water-soluble curcumin at the inflamed colon sites, while showing promise in addressing both colitis and colorectal cancer, which potentially paves the way for OC-S to advance into clinical development as a dietary product for both IBD and CRC.

From Liquid to Solid: Unravelling the Magic of In-Situ Gels

Abstract: In situ gelling formulations are liquid at room temperature and transform into gels upon application to the body in response to various stimuli (e.g., pH, temperature, ionic composition). Incorporating drug nanoparticles into these systems enhances their biomedical utility by prolonging drug release, reducing dosing frequency, and improving patient outcomes. These formulations, particularly those with mucoadhesive polymers, offer promising potential for targeted drug delivery and prolonged drug retention at specific sites. A review of clinical properties of in situ gelling systems investigated over the past decade underscores their effectiveness and challenges in achieving optimal dosage forms.

The Application of Polybutyl Cyanoacrylate (PBCA) Nanoparticles in Delivering Cancer Drugs

Overview: Cancer remains a significant global health challenge, accounting for one in eight deaths worldwide. Chemotherapy, the primary cancer treatment, is often limited by drug resistance. Optimizing therapy procedures has been suggested to improve survival and quality of life for cancer patients, including those with drug resistance. In recent years, nanotechnology has garnered significant attention for its potential in cancer treatment. Nanoparticles (NPs) are widely utilized to enhance therapeutic outcomes by improving drug bioavailability, solubility, and retention time. NPs offer essential conditions for targeted drug delivery through various delivery systems, including microcapsules or NPs. Polybutyl cyanoacrylate (PBCA) is among the most commonly used carriers for drug delivery in cancer treatment, with several studies investigating its efficacy. Methods: This article aims to review the effectiveness of PBCA as a drug delivery system in the treatment of various cancers. Results: Several studies have utilized PBCA for drug delivery in cancer treatment, indicating its potential efficacy in this regard. Conclusion: The review highlights the potential of PBCA as a promising drug delivery system for the treatment of different types of cancer.

Gastroretentive Raft Forming System for Enhancing Therapeutic Effect of Drug-Loaded Hollow Mesoporous Silica on Gastric Ulcers.

Gastric ulcers are characterized by damage to the stomach lining and are often triggered by substances such as ethanol and non-steroidal anti-inflammatory drugs. Patchouli alcohol (PA) has demonstrated effectiveness in treating gastric ulcers through antioxidative and anti-inflammatory effects. However, the water insolubility of PA and rapid gastric emptying cause low drug concentration and poor absorption in the stomach, resulting in limited treatment efficacy of PA. This study develops an oral gastroretentive raft forming system (GRFDDS) containing the aminated hollow mesoporous silica nanoparticles (NH2-HMSN) for PA delivery. The application of NH2-HMSN can enhance PA-loading capacity and water dispersibility, promoting bio-adhesion to the gastric mucosa and sustained drug release. The incorporation of PA-loaded NH2-HMSN (NH2-HMSN-PA) into GRFDDS can facilitate gastric drug retention and achieve long action, thereby improving therapeutic effects. The results reveal that NH2-HMSN-PA protects the gastric mucosa damage by inhibiting NLRP3-mediated pyroptosis. The GRFDDS, optimized through orthogonal design, demonstrates the gastric retention capacity and sustained drug release, exhibiting significant therapy efficacy in an ethanol-induced acute gastric ulcersmodel and an aspirin-induced chronic gastric ulcersmodel through antioxidation, anti-pyroptosis, and anti-inflammation. This study provides a potential strategy for enhancing druggability of insoluble natural compounds and therapeutic management of gastric ulcers.

Formulation and Evaluation of Ethosomal Cream containing Resveratrol for the Treatment of Contact Dermatitis

Objective: The aim of this study was to formulate and evaluate ethosomal cream containing resveratrol for the treatment of contact dermatitis. Method: Resveratrol-loaded ethosome was prepared using cold method. The prepared ethosomes were assessed for entrapment efficiency (%), TEM analysis and sedimentation rate to determine the optimal formulation for loading into cream base. The selected formulation was further investigated for particle size distribution and zeta potential. A cream base was formulated using fusion and trituration method and selected for loading with the ethosomal suspension, meeting specification suitable for topical delivery. Ethosomal cream formulations were evaluated for drug content, ex -vitro diffusion by using goat skin, skin retention, microbiological study and stability study. Result and Discussion: The formulation E3 was selected for loading in the optimized cream base (F4) to obtain a topical cream containing ethosomes of resveratrol. The release study reveals that release was controlled for the 24 hours. The drug release in buffer was less than 17% from all the formulations after 24 hours. The drug content of resveratrol in goat skin and cream remained in donor compartment indicates that the drug retention in skin was high in all the formulations, which is desirable for the topical formulations. The best possible release kinetics of the formulation loaded with resveratrol containing ethosomes was found to be zero order. The ‘n’ value from Peppas’s model indicated that the drug release was by Fickian diffusion. Stability study indicates that all the cream formulations were stable after a time period of one month. Conclusion: The present study conclusively supported that ethosomal cream containing resveratrol to be an advantageous topical drug delivery system in treatment of ACD. However detail in- vivo study should be conducted in future to be justify the in- vitro study. Keywords: Resveratrol, Ethosome, Cream, Contact dermatitis.

A bioactive nanocomposite integrated specific TAMs target and synergistic TAMs repolarization for effective cancer immunotherapy

Reactive oxygen species (ROS) generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages (TAMs) toward the anti-tumor M1 phenotype, representing a promising cancer immunotherapy strategy. Nevertheless, their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers. Here, a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy. Colloidal mesoporous silica nanoparticles (CMSN) are fabricated to encapsulate photosensitizer-Indocyanine Green (ICG) to improve their stability. Then ginseng-derived exosome (GsE) was coated on the surface of ICG/CMSN for targeting TAMs, as well as repolarizing TAMs concurrently, named ICG/CMSN@GsE. As expected, with the synergism of ICG and GsE, ICG/CMSN@GsE exhibited better stability, mild generation of ROS, favorable specificity toward M2-like macrophages, enhancing drug retention in tumors and superior TAMs repolarization potency, then exerted a potent antitumor effect. In vivo, experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage. Taken together, by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform, ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.

Factors associated with drug retention of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: A multicentre REVEAL cohort study.

To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study

Data on the safety of Janus kinase inhibitors (JAKis) in patients with renal impairment are lacking. This study aimed to investigate the safety of JAKis compared to biological (b) DMARDs in patients with rheumatoid arthritis (RA) and renal impairment. We used a multi-centre observational registry of patients with RA in Japan (the ANSWER cohort). We assessed the drug retention rates of b/targeted synthetic DMARDs with different modes of action (tumour necrosis factor inhibitors (TNFis), immunoglobulins fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), interleukin-6 receptor inhibitors (IL-6Ris), and JAKis) in patients with RA stratified by pre-treatment estimated glomerular filtration rate (eGFR) levels. The time to discontinuation of bDMARDs or JAKis was analysed using a multivariate Cox proportional hazards model This study included 3775 patients, who were classified into three groups (the normal group (eGFR ≥ 60 mL/min/1.73 m2): 2893 patients; CKDa group (eGFR 45–60 mL/min/1.73 m2): 551; and CKDb group (eGFR < 45 mL/min/1.73 m2): 331). In the CKDb group, the 12-month drug retention rate due to adverse events (AE) was the lowest in patients treated with JAKi (TNFi: 93.1%; IL-6Ri: 94.1%; CTLA-4-Ig: 92.3%; JAKi: 75.1%). In the normal and CKDa groups, drug retention rates due to AE were similar among patients treated with bDMARDs and JAKi. In contrast, drug retention rates due to inefficacy were similar between bDMARDs and JAKis in all groups. In the Cox-proportional model, in the CKDb group, TNFi, IL-6Ri, and CTLA-4-Ig showed lower incidence of drug discontinuation due to AE than JAKis (TNFi: hazard ratio = 0.23 (95% confidence interval 0.09–0.61), IL-6Ri: 0.34 (0.14–0.81), CTLA-4-Ig: 0.36 (0.15–0.89)). JAKis showed the lowest drug retention due to AE in patients with moderate-to-severe and severe renal impairment (eGFR < 45 mL/min/1.73 m2). Physicians should pay more attention to renal function when using JAKis than when using bDMARDs.

Healing activity of a muco-adhesive formula of Teucrium polium against acetic acid-induced oral ulcer in rats

Oral ulcers are highly common painful conditions that harmfully affect the quality of life and require long-term therapy. Muco-adhesive preparations provide efficient and convenient delivery systems that prolong the drug retention time necessary for the different stages of ulcer healing. Therefore, the study aimed to evaluate the healing activity of Teucrium polium in a muco-adhesive formula against acetic acid-induced oral ulcers in rats. Acetic acid was applied to the inner cheeks of the rats and the muco-adhesive formula was applied once daily for 14 days. Acetic acid was found to disrupt the oral tissue histological features, increase collagen deposition, induce oxidative stress through increasing malondialdehyde (MDA) levels and decreasing superoxide dismutase and catalase activities, increase the expression of the inflammatory biomarkers, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and decreased hydroxyproline content and the expression of the factors that contribute in wound healing including transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor receptor 1 (VEGFR1), and platelet-derived growth factor receptor beta (PDGFRβ). However, the daily application of a mucoadhesive formula impregnated with T. polium, significantly restored the regular histological features of the oral tissue, decreased the concentration of MDA, TNF-α, IL-6, and COX-2, increased superoxide dismutase and catalase activities, and restored the expression of TGF-β1, VEGFR1, and PDGFRβ. Therefore, T. polium extract muco-adhesive formula can be considered a potential therapy for chronic oral ulcers.

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi). Retrospective analysis was conducted on data from the ANSWER cohort comprising 3623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. Of the 3623 RA patients, 450 (12.4%) met the first two criteria of the EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared with those under 65, hazard ratio [HR] = 0.46; 95% CI: 0.31, 0.69), higher rheumatoid factor (RF) titres (HR = 1.005; 95% CI: 1.00, 1.01), higher clinical disease activity index (HR = 1.02; 95% CI: 1.01, 1.03), lower methotrexate dosage (HR = 0.97; 95% CI: 0.95, 0.99), and comorbidities like hypertension (HR = 1.53; 95% CI: 1.2, 1.95) and diabetes (HR = 1.37; 95% CI: 1.09, 1.73). Anti-IL-6 receptor antibodies (aIL-6R, HR = 0.53; 95% CI: 0.37, 0.75) and JAKi (HR = 0.64; 95% CI: 0.46, 0.90) were associated with fewer discontinuations due to ineffectiveness compared with TNF inhibitors. Oral glucocorticoid usage (HR = 1.65; 95% CI: 1.11, 2.47) was linked to increased discontinuation due to toxic adverse events. Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

PH-responsive drug-loaded peptides enhance drug accumulation and promote apoptosis in tumor cells

The efficacy of chemotherapeutic drugs in tumor treatment is limited by their toxicity and side effects due to their inability to selectively accumulate in tumor tissue. In addition, chemotherapeutic agents are easily pumped out of tumor cells, resulting in their inadequate accumulation. To overcome these challenges, a drug delivery system utilizing the amphiphilic peptide Pep1 was designed. Pep1 can self-assemble into spherical nanoparticles (PL/Pep1) and encapsulate paclitaxel (PTX) and lapatinib (LAP). PL/Pep1 transformed into nanofibers in an acidic environment, resulting in longer drug retention and higher drug concentrations within tumor cells. Ultimately, PL/Pep1 inhibited tumor angiogenesis and enhanced tumor cell apoptosis. The use of shape-changing peptides as drug carriers to enhance cancer cell apoptosis is promising.

Effects of ferrohydrodynamics on drug transport and retention in drug eluting stents

This study examines the transport of magnetized drug particles (MPs) in drug-eluting stents (DESs). The governing equations for multi-species transport in a two-domain consisting of a polymer and media are formulated and solved using the finite volume method. The effects of an external magnetic field (MF) on the distribution of different drug species are analyzed. The MF was found to increase MP concentrations in the tissue and, unexpectedly, in the polymer at the same time. This counterintuitive finding was explained by analyzing the rates of transport through the polymer topcoat and the media top-layer. It was revealed that the rates of transport into and out of the media layer initially decrease and then increase with the MF, with an intermediate regime where the dynamics resemble those without MF. The maximum averaged free drug concentration in the tissue and that of the dissolved drug in the polymer were observed to increase exponentially with the MF implying on the fact that drug delivery becomes more sensitive to the MF at its larger strength. Tracking the drug center of mass revealed a nonmonotonic variation with time consisting of two linear regimes on a time log scale. The slopes of the first regime decreases with the MF while that of the second one is unaffected by the MF. The transition time was shown to increase almost linearly with the MF. The results of this study have promising applications in palliating the tendency for low drug retention from which current DES suffers.

Rheological and Injectability Evaluation of Sterilized Poloxamer-407-Based Hydrogels Containing Docetaxel-Loaded Lipid Nanoparticles.

Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle-hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol-gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe-needle systems with acceptable force (2.2-13.4 N) and work (49.5-317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1-2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.