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Preclinical Characterization of Engineered Nanoparticles Intended for Cancer Therapeutics
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Anil K. Patri, Marina A. Dobrovolskaia, Stephan T. Stern, Scott E. McNeil
Surface characteristics contribute to the nanoparticle’s solubility, aggregation tendency, ability to traverse biological barriers (such as a cell wall), biocompatibility, and targeting ability. The nanoparticle surface is also responsible for interaction and binding with plasma proteins in vivo, which in turn may alter the nanoparticle’s distribution and pharmacokinetics. For multifunctional nanoparticles, modifying agents are often attached to the surface to bind to receptors in target tissues and organs. The presence of charged functionalities on the nanoparticle surface may increase nonspecific uptake, making the preparation less effective in targeting. It has been shown that dendrimer nanoparticles displaying positively charged amine groups on their surface can be significantly more hemolytic and cytotoxic than nanoparticles displaying negatively charged carboxylates.20 The negatively charged nanoparticles were also cleared more slowly from the blood compared to positively charged species, following intravenous administration to rats.20 Another potential effect of surface charge is to alter a nanoparticle’s ability to penetrate the blood–brain barrier. Studies have shown that for emulsifying wax nanoparticles, anionic surfaces were superior to neutral or cationic surfaces for penetration of the blood–brain barrier.33
Amphotericin B Deoxycholate
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Neil R. H. Stone, Tihana Bicanic
Pulmonary aspergillomas often require surgical treatment; however, as they often exist within preexisting pulmonary cavities patients often do not have sufficient lung function to allow for surgery. Given the frequently poor response to systemic antifungal therapy, intracavitary AMB has been used in such patients, primarily to control hemoptysis. The standard method of administration is insertion of a catheter into the cavity (usually under computed tomographic [CT] guidance), followed by instillation of 50 mg amphotericin B in 20 ml 5% dextrose solution daily for 10 days (Kravitz et al., 2013). A total of 800 mg AMB has been used in patients with ongoing hemoptysis (Cochrane et al., 1991) and in one case 3 g over 60 days was given in a cystic fibrosis patient, using the smaller volume of 10 ml for the instillation (Ryan et al., 1995). Administration of 50 mg AMB in 10 ml 5% dextrose followed by 8 mg bromhexine in 10 ml saline has also been used (Lee et al., 1993). N-acetylcysteine (10% solution, 10 ml dissolved in 10 ml 0.9% saline) has also been used, given 8–12 hours following AMB instillation, to facilitate dissolution of the fungus ball. The catheter was placed on low continuous wall suction (20 cm H2O) 2 hours after administration of N-acetylcysteine and maintained overnight. An alternative method of intracavitary administration of AMB has been described as a substitute for repeated injections (Munk et al., 1993). An AMB gelatin mixture formed by dissolving 6 g oxoid laboratory standard gelatin in 8.5 ml sterile water, using a hot water bath at 40°C, was prepared. Immediately before injection, 15 mg AMB was then dissolved in this mixture and drawn up in a syringe that had been warmed in the hot water bath. A needle was placed in the cavity under CT or fluoroscopic guidance, and the viscous mixture injected rapidly as it solidifies quickly. This single administration resulted in complete resolution of three out of four pulmonary aspergillomas within 3 months, with no evidence of recurrence at 6–18 months (Munk et al., 1993). Another method was described using a paste formed by mixing AMB (1–5 vials depending on the size of the cavity) with the lipid compound Lipiodol (2.4 ml) and Suppocire C, an emulsifying wax. The paste was then instilled into the lung cavity. Most patients required several injections at 1–3 week intervals. Twenty-six of 40 aspergillomas disappeared with this method (Giron et al., 1998). Instillation can cause coughing, which has been successfully relieved by instilling lignocaine 1% into the cavity (Ryan et al., 1995).
A topical formulation containing quercetin-loaded microcapsules protects against oxidative and inflammatory skin alterations triggered by UVB irradiation: enhancement of activity by microencapsulation
Published in Journal of Drug Targeting, 2021
David L. Vale, Renata M. Martinez, Daniela C. Medeiros, Camila da Rocha, Natália Sfeir, Renata F. V. Lopez, Fabiana T. M. C. Vicentini, Waldiceu A. Verri, Sandra R. Georgetti, Marcela M. Baracat, Rúbia Casagrande
Formulation was prepared using: i) the self-emulsifying wax Polawax® (cetostearyl alcohol and polyoxyethylene derived of a fatty acid ester of sorbitan 20 0E) (10%); ii) the emollient caprylic/capric triglyceride (5%); iii) the solubilising agent and moisturiser propylene glycol (6%); iv) the preservative phenonip (0.4%); v) deionised water to complete 100% of formulation. QC (0.5%), QC-loaded microcapsules (adjusted to result in a concentration of 0.5% of quercetin in the final cream) and QC-unloaded microcapsules were dispersed in propylene glycol, and then, under room temperature, added to the formulations. The control formulation without QC was named TFC; formulation with QC for topical administration was named TFQC; topical formulation containing unloaded-microcapsules was named TFuMQ and topical formulation containing QC-loaded microcapsules was named TFcQCMC for an easy differentiation among groups.
Preparation of emulsifying wax/glyceryl monooleate nanoparticles and evaluation as a delivery system for repurposing simvastatin in bone regeneration
Published in Drug Development and Industrial Pharmacy, 2018
Aaron Eskinazi-Budge, Dharani Manickavasagam, Tori Czech, Kimberly Novak, James Kunzler, Moses O. Oyewumi
We considered that nanoparticle (NP)-based delivery systems will offer many intriguing opportunities for Sim application in bone regeneration, and these include (1) the large surface area-to-volume ratio that will facilitate availability of entrapped Sim during bone regeneration, (2) capability of achieving bone targeted and/or controlled release of entrapped bone osteoinductive agents, (3) amenability to administration via local or systemic routes, and (4) ease of inclusion of NPs in bone nanocomposite scaffold materials such as collagen or hydroxyapatite. Of particular interest to us are NP systems that can be prepared using nano-microemulsions as precursors [31–34]. We have earlier reported the attractive qualities of lipid NPs that are prepared through the nano-microemulsion process [31–34]. These include (1) application of scalable process [35], (2) suitability for drug entrapment within the oil-in-water nanoemulsion template, (3) application of matrix materials that are biocompatible and biodegradable (FDA approved in the category of ‘generally regarded as safe’ (GRAS)) [36]. In the current study, we developed lipid NPs for Sim delivery using binary mixtures of glyceryl monooleate (GMO) and emulsifying wax (Ewax) as matrix materials. In previous studies, we have developed NPs made with Ewax alone, which is comprised of cetyl alcohol and polysorbate 60 [35]. We later observed that application of binary blends of matrix materials could improve NP formation, colloidal stability, and entrapment of drug in the nanoemulsion templates [31–34]. The rationale for selecting GMO in NP preparation was based on many attractive qualities that we envisaged would facilitate Sim entrapment and NP preparation as well as ensure colloidal stability [37,38]. GMO is an amphiphilic excipient that is classified as GRAS and included in FDA Inactive Ingredients Guide. GMO is prepared by esterification of glycerol with fatty acids [39,40]. In addition, GMO belongs to a class of water-insoluble lipids which swells in water and forms various kinds of lyotropic liquid crystals [41,42]. As such, we envisioned that the unique properties of GMO can be exploited in preparing stable drug-loaded oil-in-water nanoemulsion templates that will translate into stable NP preparations. It is expected that the NPs prepared with binary mixtures of Ewax and GMO will be stable and biocompatible. As such, stable NPs loaded with Sim were engineered from oil-in-water nanoemulsions that were prepared using the modified method that we previously reported [34,43,44]. The effectiveness of NPs as delivery systems for Sim was evaluated based on size, stability, entrapment efficiency, size distribution, drug release kinetics as well as efficacy of released drug to induce differentiation and function of osteoblasts, and/or inhibit the differentiation and functions of osteoclasts.