Enhanced Skin Permeation of 5-Fluorouracil through Drug-in-Adhesive Topical Patches.

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles.

Printing a cure: A tailored solution for localized drug delivery in liver cancer treatment.

Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy.

Combining the potential of 3D printed buccal films and nanostructured lipid carriers for personalised cannabidiol delivery.

Cannabidiol (CBD) has been recognized for its numerous therapeutic benefits, such as neuroprotection, anti-inflammatory effects, and cardioprotection. However, CBD has some limitations, including unpredictable pharmacokinetics and low oral bioavailability. To overcome the challenges associated with CBD delivery, we employed Design of Experiments (DoE), lipid carriers, and 3D printing techniques to optimize and develop buccal film loaded with CBD-NLCs. Three-factor Box-Behnken Design was carried out to optimise the NLCs and analyse the effect of independent factors on dependent factors. The emulsification-ultrasonication technique was used to prepare the NLCs. A pressure-assisted micro-syringe printing technique was used to produce the films. The produced films were studied for physicochemical, and mechanical properties, release profiles, and predicted in vivo performance. The observed particle size of the NLCs ranged from 12.17 to 84.91 nm whereas the PDI varied from 0.099 to 0.298. Lipid and sonication time positively affected the particle size whereas the surfactant concentration was inversely related. CBD was incorporated into the optimal formulation and the observed particle size, PDI, and zeta potential for the CBD-NLCs were 94.2 ± 0.47 nm, 0.11 ± 0.01 and - 11.8 ± 0.52 mV. Hydroxyethyl cellulose (HEC)-based gel containing the CBD-NLCs was prepared and used as a feed for 3D printing. The CBD-NLCs film demonstrated a slow and sustained in vitro release profile (84. 11 ± 7.02% in 6 h). The predicted AUC0-10 h, Cmax, and Tmax were 201.5 µg·h/L, 0.74 µg/L, and 1.28 h for a film with 0.4 mg of CBD, respectively. The finding demonstrates that a buccal film of CBD-NLCs can be fabricated using 3D printing.

Innovative Topical Patches for Non-Melanoma Skin Cancer: Current Challenges and Key Formulation Considerations.

Non-melanoma skin cancer (NMSC) is the most prevalent malignancy worldwide, with approximately 6.3 million new cases worldwide in 2019. One of the key management strategies for NMSC is a topical treatment usually utilised for localised and early-stage disease owing to its non-invasive nature. However, the efficacy of topical agents is often hindered by poor drug penetration and patient adherence. Therefore, various research groups have employed advanced drug delivery systems, including topical patches to overcome the problem of conventional topical treatments. This review begins with an overview of NMSC as well as the current landscape of topical treatments for NMSC, specifically focusing on the emerging technology of topical patches. A detailed discussion of their potential to overcome the limitations of existing therapies will then follow. Most importantly, to the best of our knowledge, this work unprecedentedly combines and discusses all the current advancements in innovative topical patches for the treatment of NMSC. In addition to this, the authors present our insights into the key considerations and emerging trends in the construction of these advanced topical patches. This review is meant for researchers and clinicians to consider utilising advanced topical patch systems in research and clinical trials toward localised interventions of NMSC.

Nanotechnology and narasin: a powerful combination against acne.

Acne vulgaris is widely regarded as the most prevalent skin disorder characterized by painful, inflammatory skin lesions that are primarily attributed to the pathogenic actions of Cutibacterium acnes (C. acnes). To improve the clinical management of this disease, there is a pressing clinical demand to develop innovative antibacterial therapies that utilize novel mechanisms. The current research aimed to discover the antibacterial efficacy of narasin (NAR), a polyether ionophore, against drug-resistant acne bacteria. In addition, the study aimed to formulate self-nanomicellizing solid dispersions (SNMSD), utilizing Soluplus® (SOL), as a drug delivery system to incorporate NAR and selectively target the lipophilic C. acnes abundant environments within the skin. Furthermore, the study aimed to investigate the ex vivo deposition and permeation of NAR into the various layers of the skin using full-thickness porcine ear skin as a model skin. By encapsulating NAR within spherical polymeric micelles (dn < 80 nm) aqueous solubility was significantly increased by approximately 100-fold (from <40 µg mL-1 to 4600 µg mL-1). Following optimization, the micelle solution was integrated into a gel formulation (containing 0.2% w/v NAR) and evaluated for stability over 4 weeks at room temperature (drug content >98%). Results from drug deposition and permeation experiments demonstrated that the deposition of NAR from the NAR-micelle solution and its gel formulation into the lipophilic stratum corneum (19 835.60 ± 6237.89 ng cm-2 and 40 601.14 ± 3736.09 ng cm-2) and epidermis (19 347 ± 1912.98 ng cm-2 and 18 763.54 ± 580.77 ng cm-2) was superior to that of NAR in solution, which failed to penetrate any skin layers. In conclusion, the outcomes of this study provide evidence that NAR exhibits promising activity against antimicrobial resistant strains of C. acnes (MIC range ≤0.008-0.062) and that micelle nanocarriers can improve the aqueous solubility of poorly water-soluble drugs. Furthermore, our results highlight the ability of nanomicelles to enable selective and targeted drug delivery to the lipophilic skin layers.

Perceptions and expectations of health professionals regarding hospital pharmacy services and the roles of hospital pharmacists: A qualitative systematic review and meta-synthesis.

Background: Pharmacists have become increasingly integrated within the interprofessional hospital team as their scope of practice expanded in recent decades. However, limited research has explored how the roles of hospital pharmacists are perceived by other health professionals. Aim/Objectives: To identify what is known about the perceptions of hospital pharmacists' roles and hospital pharmacy services held by non-pharmacist health professionals. Methods: A systematic literature search was conducted in August 2022 in MEDLINE, Embase, and CINAHL to identify peer-reviewed articles published between 2011 and 2022. Title/abstract and full-text screening, by two independent reviewers, identified eligible articles. Inclusion criteria included qualitative studies in hospital settings that reported perceptions regarding the roles of hospital pharmacists held by non-pharmacist health professionals. Data were extracted using a standardised extraction tool. Collated qualitative data underwent inductive thematic analysis by two independent investigators to identify codes, which were reconciled and merged into over-arching themes through a consensus process. Findings were assessed to measure confidence using the GRADE-CERQual criteria. Results: The search resulted in 14,718 hits. After removing duplicates, 10,551 studies underwent title/abstract screening. Of these, 515 underwent full-text review, and 36 were included for analysis. Most studies included perceptions held by medical or nursing staff. Hospital pharmacists were perceived as valuable, competent and supportive. At an organisational level, the roles of hospital pharmacists were perceived to benefit hospital workflow and improve patient safety. Roles contributing to all four domains of the World Health Organization's Strategic Framework of the Global Patient Safety Challenge were recognised. Highly-valued roles include medication reviews, provision of drug information, and education for health professionals. Conclusion: This review describes the roles hospital pharmacists performed within the interprofessional team, as reported by non-pharmacist health professionals internationally. Multidisciplinary perceptions and expectations of these roles may guide the prioritisation and optimisation of hospital pharmacy services.

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach.

Background: Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Methods: Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. Results: In this study, stearyl alcohol, oleic acid, Tween® 80 (polysorbate 80), and Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm2 and 12.3 ± 2.2 µg/cm2, while the commercial cream only deposited 1.0 ± 0.8 µg/cm2 and 1.5 ± 0.5 µg/cm2 of IMQ, respectively. Conclusion: In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.

pH and its applications in targeted drug delivery.

Physiologic pH is vital for the normal functioning of tissues and varies in different parts of the body. The varying pH of the body has been exploited to design pH-sensitive smart oral, transdermal and vaginal drug delivery systems (DDS). The DDS demonstrated promising results in hard-to-treat diseases such as cancer and Helicobacter pylori infection. In some cases, a change in pH of tissues or body fluids has also been employed as a useful diagnostic biomarker. This paper aims to comprehensively review the development and applications of pH-sensitive DDS as well as recent advances in the field.

Effect of plasticizers on drug-in-adhesive patches containing 5-fluorouracil.

Topical patches containing 5-fluorouracil (5-FU) are a feasible alternative to overcome the shortcomings of commercial cream for the treatment of non-melanoma skin cancer (NMSC). Plasticizers are a critical component of drug-in-adhesive (DIA) patches as they can significantly affect the mechanical, adhesive and drug release characteristics of the patches. Eudragit® E (EuE) is a methacrylate-based cationic copolymer capable of producing flexible and adhesive films for topical application. In this study, the effect of plasticizers on the mechanical, adhesive and 5-FU release characteristics of EuE-based patches was comprehensively evaluated. While the elongation at break (%) and adhesion of the films were significantly increased with increasing triacetin, dibutyl sebacate (DBS) and triethyl citrate (TEC) concentrations, the tensile strength showed an inverse relationship. EuE plasticized with 40% triacetin, 30% DBS or 40% w/w TEC produced elastic and adhesive films most suitable for topical application. In vitro release studies of the 5-FU-loaded patches demonstrated an initial burst release pattern during the first 10 min followed by a slow release over 120 min. In summary, this study provides important information on effect of plasticizers for preparation of EuE-based patches with desired mechanical, adhesive and release characteristics of 5-FU towards their potential application in the treatment of NMSC.

Antioxidant and Antiglycation Activities of Syzygium paniculatum Gaertn and Inhibition of Digestive Enzymes Relevant to Type 2 Diabetes Mellitus.

Advanced glycation end-products (AGEs) may be a contributing factor in the development of diabetes-specific vascular pathologies that affect the retina, glomerulus and peripheral nerves. In this study, Australian native food plant species Syzygium paniculatum was investigated for activities relevant to Type 2 diabetes mellitus including inhibition of α-amylase, α-glucosidase and protein glycation. A methanolic extract of the leaves showed the strongest α-amylase inhibition (IC50 = 14.29 ± 0.82 µg/mL, p < 0.05) when compared with other extracts. For inhibition of α-glucosidase, the strongest inhibition was shown for the water, methanolic and acetone extracts of leaves with IC50 values ranging from 4.73 ± 0.96 to 7.26 ± 0.92 µg/mL. In the BSA-glucose model, fruit and leaf extracts inhibited formation of protein-bound fluorescent AGEs with IC50 values ranging between 11.82 ± 0.71 and 96.80 ± 13.41 µg/mL. Pearson's correlation analysis showed that the AGE inhibition significantly correlated with DPPH (rp = -0.8964, p < 0.05) and ABTS (rp = -0.8326, p < 0.05). α-amylase inhibitory activities strongly correlated with DPPH (rp = -0.8964, p < 0.001). α-glucosidase inhibition strongly correlated with TPC (rp = -0.9243, p < 0.05), FRAP (rp = -0.9502, p < 0.01), DPPH (rp = -0.9317, p < 0.01) and ABTS (rp = -0.9486, p < 0.01). This study provides a strong rationale for further investigation aimed at isolating and identifying the active compounds responsible for the observed effects on targets relevant to diabetes.