scholarly journals Affinity-based polymers provide long-term immunotherapeutic drug delivery across particle size ranges optimal for macrophage targeting

2019 ◽  
Author(s):  
Nathan A. Rohner ◽  
Linda Purdue ◽  
Horst A. von Recum

AbstractLong term drug delivery to specific arms of the immune system can be technically challenging to provide limited off-target toxicity as well as prolonged delivery and specific cellular targeting given the limits of current drug delivery systems. In this work, we demonstrate the robustness of a cyclodextrin (CD) polymer platform that can extend immunomodulatory drug delivery via affinity interactions to promote long-term, sustained release at multiple size scales. The parameter space of synthesis variables (pre-incubation and stirring speed) and post-synthesis grinding effects on resulting particle diameter were characterized. We demonstrate that polymerized CD forms exhibit size-independent release profiles of the small molecule drug lenalidomide (LND) and can provide similar drug delivery profiles as macro-scale CD polymer disks. CD polymer microparticles and nanoparticles demonstrated no significant cytotoxicity as compared to the base CD macromonomer when co-incubated with fibroblasts. Uptake of ground CD nanoparticles was significantly higher following incubation with RAW 264.7 macrophages in culture over originally synthesized, larger CD microparticles. Thus, the affinity/structure properties afforded by polymerized CD allow particle size to be modified to affect cellular uptake profiles independently of drug release rate for applications in cell-targeted drug delivery.

2013 ◽  
Vol 6 (6) ◽  
pp. 10269-10295 ◽  
Author(s):  
M. I. A. Berghof ◽  
G. P. Frank ◽  
S. Sjogren ◽  
B. G. Martinsson

Abstract. The droplet aerosol analyzer (DAA) was developed to study the influence of aerosol properties on clouds. It measures the ambient particle size of individual droplets and interstitial particles, the size of the dry (residual) particles after the evaporation of water, and the number concentration of the dry (residual) particles. A method was developed for the evaluation of DAA data to obtain the three-parameter dataset: ambient particle diameter, dry (residual) particle diameter and number concentration. First results from in-cloud measurements performed on the summit of Mt. Brocken in Germany are presented. Various aspects of the cloud aerosol dataset are presented, such as the number concentration of interstitial particles and cloud droplets, the dry residue particle size distribution, droplet size distributions, scavenging ratios due to cloud droplet formation and size-dependent solute concentrations. This dataset makes it possible to study clouds and the influence of the aerosol population on clouds.


Author(s):  
Dipti Gohil ◽  
Krupa Patel ◽  
Kruti Patel ◽  
Shivani Tiwari ◽  
Priyank Patel ◽  
...  

Microsponge is developing field of technology which can achieve goal of site specific as well as controlled drug delivery. Physicochemical properties of microsponge like Particle size, particle size distribution, porosity, surface morphology plays a major role in selection of type of dosage form and route of administration for delivery of drug. Microsponge is also emerged as novel tool for delivering of drug by topical route. Topical route is having added advantage of formulation flexibility, greater patient compliance, improved safety and efficacy of formulation and aesthetic properties. Rheumatoid Arthritis is immunomodulatory disease which requires long term treatment for management of disease. Available oral formulation may cause liver toxicity upon long term use. Topical route can be suitable alternate route for delivery of drug with enhanced stability of drug, reduced side effects, and reduced frequency of administration. Due to porous and spongy structure of Microsponge, it has the capacity to entrap large amount of dose and can modify drug release too.


2018 ◽  
Vol 5 (3) ◽  
pp. 175-187 ◽  
Author(s):  
O. V. Gorovtsova ◽  
T. L. Ushakova ◽  
V. G. Polyakov

Retinoblastoma is one of highly curable diseases; today the total 5-year survival rate in patients with retinoblastoma exceeds 95%. The article summarizes the current world experience on treatment of patients with intraocular retinoblastoma. The treating skills of intraocular malignant tumor in children are a balance between the patient’s life and the preservation of an eye and its visual functions. The complex and challenging task is the treatment of common intraocular retinoblastoma groups «C», «D», «E» when the large size or localization of the tumor does not allow performing the local (focal) destruction of the tumor. As a rule, in such cases neoadjuvant chemotherapy (CT) is performed at the first stage in order to reduce the size of the tumor for further focal therapy. However, the analysed data on the effectiveness of neoadjuvant CT in combination with focal or radiotherapy demonstrated the limited possibilities of the proposed therapy. Local drug delivery in cancer therapy became a real breakthrough in the organ-preserving treatment of children with large intraocular retinoblastoma. The most widely used current methods of local drug delivery are intravitreal (IVitC) and selective intra-arterial chemotherapy (SIAC) as monotherapy or in combination with neoadjuvant CT and focal therapy which significantly increased the percentage of preserved eyes without radiotherapy administration or damage to the patient survival. The review discusses the different IVitC and SIAC techniques, chemotherapy schemes, dosages of chemotherapy, immediate and long-term complications of treatment.


Author(s):  
Nisha Patel ◽  
Hitesh A Patel

In this study, we sought to improve the dissolution characteristics of a poorly water-soluble BCS class IV drug canaglifozin, by preparing nanosuspension using media milling method. A Plackett–Burman screening design was employed to screen the significant formulation and process variables. A total of 12 experiment were generated by design expert trial version 12 for screening 5 independent variables namely the amount of stabilizer in mg (X1), stirring time in hr (X2), amt of Zirconium oxide beads in gm (X3), amount of drug in mg (X4) and stirring speed in rpm (X5) while mean particle size in nm (Y1) and drug release in 10 min. were selected as the response variables. All the regression models yielded a good fit with high determination coefficient and F value. The Pareto chart depicted that all the independent variables except the amount of canaglifozin had a significant effect (p<0.001) on the response variables. The mathematical model for mean particle size generated from the regression analysis was given by mean particle size = +636.48889 -1.28267 amt of stabilizer(X1) -4.20417 stirring time (X2) -7.58333 amt of ZrO2 beads(X3) -0.105556 amt of drug(X4) -0.245167 stirring speed(X5) (R2=0.9484, F ratio=22.07, p<0.001). Prepared canaglifozin nanosuspension exemplified a significant improvement (p<0.05) in the release as compared to pure canaglifozin and marketed tablet with the optimum formulation releasing almost 80% drug within first 10min. Optimized nanosuspension showed spherical shape with surface oriented stabilizer molecules and a mean particle diameter of 120.5 nm. There was no change in crystalline nature after formulation and it was found to be chemically stable with high drug content.


2020 ◽  
Vol 27 (22) ◽  
pp. 3623-3656 ◽  
Author(s):  
Bruno Fonseca-Santos ◽  
Patrícia Bento Silva ◽  
Roberta Balansin Rigon ◽  
Mariana Rillo Sato ◽  
Marlus Chorilli

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.


2020 ◽  
Vol 17 ◽  
Author(s):  
Anisha D’Souza ◽  
Ranjita Shegokar

: In recent years, SLNs and NLCs are among the popular drug delivery systems studied for delivery of lipophilic drugs. Both systems have demonstrated several beneficial properties as an ideal drug-carrier, optimal drug-loading and good long-term stability. NLCs are getting popular due to their stability advantages and possibility to load various oil components either as an active or as a matrix. This review screens types of oils used till date in combination with solid lipid to form NLCs. These oils are broadly classified in two categories: Natural oils and Essential oils. NLCs offer range advantages in drug delivery due to the formation of imperfect matrix owing to the presence of oil. The type and percentage of oil used determines optimal drug loading and stability. Literature shows that variety of oils is used in NLCs mainly as matrix, which is from natural origin, triglycerides class. On the other hand, essential oils not only serve as a matrix but as an active. In short, oil is the key ingredient in formation of NLCs, hence needs to be selected wisely as per the performance criteria expected.


Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 121
Author(s):  
Noriko Yamaguchi ◽  
Toshiaki Ohkura ◽  
Atsuko Hikono ◽  
Yohey Hashimoto ◽  
Aomi Suda ◽  
...  

Global concerns for the sustainability of agriculture have emphasized the need to reduce the use of mineral fertilizer. Although phosphorus (P) is accumulated in farmland soils due to the long-term application of fertilizer, most soil P is not readily available to plants. The chemical speciation of P in soils, which comprise heterogeneous microenvironments, cannot be evaluated with a high degree of specificity using only macroscopic analyses. In this study, we investigated the distribution and speciation of P accumulated in soils by using both macro- and microscopic techniques including chemical extraction, solution and solid-state 31P NMR, bulk- and micro- P K-edge X-ray absorption near edge structure (XANES), and electron probe microanalysis (EPMA). Soil samples were collected from a field in which cabbage was cultivated under three amendment treatments: i) mineral fertilizer (NPK), ii) mineral fertilizer and compost (NPK + compost), and iii) mineral fertilizer plus compost but without nitrogen fertilizer (PK + compost). Macro-scale analyses suggested that accumulated P was predominantly inorganic P and associated with Al-bearing minerals. The repeated application of compost to the soils increased the proportion of P associated with Ca which accounted for 17% in the NPK + compost plot and 40% in the PK + compost plot. At the microscale, hot spots of P were heterogeneously distributed, and P was associated with Fe and Ca in hot spots of the NPK + compost (pH 6) and PK + compost (pH 7) treated samples, respectively. Our results indicate that application of compost contributed to creating diverse microenvironments hosting P in these soils.


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