Bone metastasis is a devastating complication of cancer that requires an immediate attention. Although our understanding of the metastatic process has improved over the years, yet a number of questions still remain unanswered, and more research is required for complete understanding of the skeletal consequences of metastasis. Furthermore, as no effective treatments are available for some of the most common skeleton disorders such as arthritis, osteoarthritis, osteosarcoma and metastatic bone cancer, there is an urgent need to develop new drugs and drug delivery systems for safe and efficient clinical treatments. Hence this article describes the potential of targeted delivery platforms aimed specifically at bone metastasized tumors. The review gives a brief understanding of the proposed mechanisms of metastasis and focuses primarily on the targeting moieties such as bisphosphonates, which represent the current gold standard in bone metastasis therapies. Special focus has been given to the targeted nanoparticulate systems for treating bone metastasis and its future. Also highlighted are some of the therapeutic targets that can be exploited for designing therapies for bone metastasis. Some of the patented molecules for bone metastasis prevention and treatment have also been discussed. Recently proposed HIFU-CHEM, which utilizes High Intensity Focused ultrasound (HIFU) guided by MRI in combination with temperature-sensitive nanomedicines has also been briefed. The study has been concluded with a focus on the innovations requiring an immediate attention that could improve the treatment modality of bone metastasis.
Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion–evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box–Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN “S8” were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in C max and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized.
Objective: Diclofenac diethylamine (DDEA) loaded solid lipid nanoparticles (SLN) were developed and incorporated in to transmucosal patch (TP) for application in dental surgeries. Methods: DDEA-SLNs were prepared by solvent emulsion evaporation method with compritol 888 ATO as lipid and soya lecithin, Pluronic F68 as surfactants and optimized by a 3-factor 3-level central composite design for its impact on particle size (PS) and entrapment efficiency (EE). SLN was incorporated into a bilayer TP prepared with hydroxypropyl cellulose -LF and polycarbophil along with Labrafac as plasticizer. TP was characterized for tensile and mucoadhesive strength, FTIR, DSC, XRD, SEM, in vitro and ex vivo release. Results: PS, EE, in vitro and ex vivo release of the optimized SLN batch D6 were found to be 178.88 ± 1.3 nm, 54.14 ± 1.6%, 98.26 ± 3.4% and 96.28 ± 3.5% at 24 h respectively. TP showed 99.22 ± 0.7% of in vitro release and 99.53 ± 0.9% permeation through porcine mucosa at 24 h with satisfactory tensile strength and mucoadhesive properties. Conclusion: The designed once a day TP loaded with DDEA-SLN applied at the gingival site, immediately after dental surgery has the potential to produce therapeutic relief locally which is prolonged for 24 h, with the added advantage of overcoming first pass metabolism and gastric irritation, in addition to decreasing the frequency of administration of Diclofenac.
International Journal of Nanomedicine Dovepress submit your manuscript | www.dovepress.com Dovepress 1867 C o r r I g e N d u m open access to scientific and medical research open Access Full Text Article
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.