scholarly journals NANOEMULSIONS FOR PROSTRATE CANCER THERAPY: AN OVERVIEW

2017 ◽  
Vol 10 (5) ◽  
pp. 37
Author(s):  
Manikandan P ◽  
Sundara Ganapathy R
Keyword(s):  
Prostate Cancer ◽  
Oral Delivery ◽  
Water Solubility ◽  
Oral Absorption ◽  
Solid Dispersions ◽  
Dose Proportionality ◽  
Permeation Enhancers ◽  
Lipophilic Drugs ◽  
Prostrate Cancer ◽  
Gastric Fluids

The objective of this review is to focus the inferences of low/poor bioavailability and lack of dose proportionality for the oral delivery of drugs in prostatecancer therapy. To overcome such problems, various formulation strategies has been reported including various methods for the use of surfactants,cyclodextrins, solid dispersions, micronization, permeation enhancers, and lipids. Flutamide is an antiandrogen drug and used for the therapy of prostate cancer. The flutamide drug is having limited clinical application due to its poor water solubility and needs enhancement of its dissolution rate in simulated gastric fluids. The lipid-based formulations such as nanoemulsion have been shown to improve the solubility and oral absorption of lipophilic drugs. To conclude, this article emphasizes the various approaches of nanoemulsion based formulation for prostate cancer therapy.Keywords: Nanoemulsion, Prostate cancer, Flutamide, Antiandrogen drug, Lipophilic drugs.

scholarly journals Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 561 ◽  
Author(s):  
Maharjan ◽  
Kim ◽  
Jin ◽  
Ko ◽  
Song ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Oral Delivery ◽  
Water Solubility ◽  
Vision Loss ◽  
Oral Absorption ◽  
Aqueous Solubility ◽  
Oral Formulation ◽  
Preclinical Study ◽  
Age Related Macular Degeneration ◽  
Age Related

As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.

Nanostructured lipid carriers- A versatile carrier for oral delivery of lipophilic drugs

2020 ◽  
Vol 14 ◽  
Author(s):  
Priyanshi Patel ◽  
Mitali Patel
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Water Solubility ◽  
Oral Formulation ◽  
Lipid Nanoparticles ◽  
Nanostructured Lipid Carriers ◽  
Lipophilic Drugs ◽  
Promising Tool ◽  
Pharmaceutical Industries

Background: Around 40% of newly discovered chemical entities in pharmaceutical industries have poor water solubility and hence they suffer from low oral bioavailability owing to undesirable physicochemical and pharmacokinetic properties. So, it is the challenge for the formulation scientists to develop the oral formulation that can mitigate the pitfalls associated with such lipophilic drugs. Methods: Lipid nanoparticles hold a promising tool to augment the pitfalls of lipophilic drugs as lipid component can effectively increases the absorption of drugs which leads to improvement in oral bioavailability. They are also considered as safe because they are made up of physiological lipids which are biocompatible and biodegradable in nature. Amongst the lipid nanoparticles, Nanostructured lipid carriers (NLCs) are the second-generation lipid nanoparticle and were developed to conquer the limitations of solid lipid nanoparticles. They increase the solubility, permeability, reduce metabolism, P-glycoprotein efflux and thereby increase the bioavailability of poorly soluble drugs. Conclusion: This review highlights the various aspects of NLCs such as formulation components, types, in vivo fate, Pharmacokinetic, toxicity, recent advances and patent review of NLCs in drug delivery.

scholarly journals PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1605
Author(s):  
Maedeh Koohi Moftakhari Esfahani ◽  
Seyed Ebrahim Alavi ◽  
Peter J. Cabot ◽  
Nazrul Islam ◽  
Emad L. Izake
Keyword(s):  
Prostate Cancer ◽  
Targeted Delivery ◽  
Water Solubility ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carrier ◽  
Spherical Shape ◽  
Prostrate Cancer ◽  
Treat Prostate Cancer ◽  
Cytotoxicity Effects

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Development and Oral Bioavailability of Self-Emulsifying Formulation of Ketoconazole

2013 ◽  
Vol 5 (4) ◽  
pp. 1858-1865
Author(s):  
Arundhati Bhattacharyya ◽  
M Bajpai
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Aqueous Suspension ◽  
Droplet Diameter ◽  
Tween 80 ◽  
Concurrent Administration ◽  
System Maintenance ◽  
Pure Drug ◽  
Ph Dependent

Ketoconazole is an imidazole antifungal drug belonging to the class II of Biopharmaceutic Classification System. Maintenance of gastric acidity is essential for adequate dissolution and absorption of ketoconazole. Concurrent administration of antacid and antiulcer preparations decreases the oral absorption of ketoconazole often causing therapeutic failure.  The aim of this study was to evaluate whether a self-emulsifying formulation of ketoconazole would be able to overcome the pH dependent dissolution and oral bioavailability. Self-emulsifying drug delivery system (SEDDS) was prepared after selecting the oil, surfactant and co-surfactant by solubility analysis. Optimum ratio of the components was finalized on the basis of drug content, self-emulsification and mean droplet diameter. The effect of pH on dissolution was studied in comparison to the pure drug. Oral bioavailability was determined in comparison to aqueous suspension in rats and the effect of co-administration of ranitidine hydrochloride solution and a commercially available liquid antacid preparation was studied. The optimized formulation containing 20% Capryol 90 and 40% each of Carbitol and Tween 80, exhibited 100% drug release regardless of the pH whereas the pure drug exhibited a highly pH dependent dissolution. The AUC0-24 resulted with oral administration of the SEDDS formulation was about 34%, 43% and 60% higher compared to the aqueous suspension when administered alone, administered with ranitidine and administered with antacid respectively. The results of the present study demonstrate that self-emulsifying formulations can be utilized for oral delivery of weakly basic drugs like ketoconazole which exhibit pH dependent dissolution.

scholarly journals Piroxicam Loading onto Mesoporous Silicas by Supercritical CO2 Impregnation

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2500
Author(s):  
Marta Gallo ◽  
Luca Serpella ◽  
Federica Leone ◽  
Luigi Manna ◽  
Mauro Banchero ◽  
...  
Keyword(s):  
Supercritical Co2 ◽  
Water Solubility ◽  
Solid Dispersions ◽  
Mesoporous Silicas ◽  
Incipient Wetness Impregnation ◽  
Pore Blocking ◽  
Physico Chemical ◽  
Adsorption From Solution ◽  
First Time ◽  
Loading Procedure

Piroxicam (PRX) is a commonly prescribed nonsteroidal anti-inflammatory drug. Its efficacy, however, is partially limited by its low water solubility. In recent years, different studies have tackled this problem and have suggested delivering PRX through solid dispersions. All these strategies, however, involve the use of potentially harmful solvents for the loading procedure. Since piroxicam is soluble in supercritical CO2 (scCO2), the present study aims, for the first time, to adsorb PRX onto mesoporous silica using scCO2, which is known to be a safer and greener technique compared to the organic solvent-based ones. For comparison, PRX is also loaded by adsorption from solution and incipient wetness impregnation using ethanol as solvent. Two different commercial mesoporous silicas are used (SBA-15 and Grace Syloid® XDP), which differ in porosity order and surface silanol population. Physico-chemical analyses show that the most promising results are obtained through scCO2, which yields the amorphization of PRX, whereas some crystallization occurs in the case of adsorption from solution and IWI. The highest loading of PRX by scCO2 is obtained in SBA-15 (15 wt.%), where molecule distribution appears homogeneous, with very limited pore blocking.

scholarly journals Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 101 ◽  
Author(s):  
Michael Brunsteiner ◽  
Johannes Khinast ◽  
Amrit Paudel
Keyword(s):  
Molecular Dynamics ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Dynamics Simulation ◽  
Limiting Factor ◽  
Poorly Soluble Drugs ◽  
Formulation Development ◽  
Amorphous Solid Dispersions ◽  
Poorly Soluble

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here, we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer–small molecule drug combinations for which stability data are available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

Abstract 13307: An Oral Antisense Oligonucleotide for PCSK9 Inhibition in Humans

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Peter Gennemark ◽  
Katrin Walter ◽  
Niclas Clemmensen ◽  
Dinko Rekic ◽  
Catarina Nilsson ◽  
...  
Keyword(s):  
Steady State ◽  
Oral Administration ◽  
Antisense Oligonucleotide ◽  
Oral Delivery ◽  
Permeation Enhancers ◽  
Pcsk9 Inhibitors ◽  
Liver Uptake ◽  
Pcsk9 Inhibition ◽  
Intestinal Permeation ◽  
Intestinal Permeation Enhancers

Current PCSK9 inhibitors are administered via subcutaneous (SC) injection. Here, we present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier ASO chemistries and intestinal permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by tri-antennary N -acetyl galactosamine (GalNAc) conjugation make this ASO highly potent. A single SC dose of 90 mg reduces PCSK9 by >90% in humans with elevated LDL-C (A), and a once monthly SC dose of 25 mg ([20, 30], 90% CI) is predicted to reduce PCKS9 by 80% at steady-state. To investigate the feasibility of oral administration, we developed an oral solid tablet wherein the ASO is co-formulated with a transient permeation enhancer. Repeated oral daily dosing of tablets to dogs resulted in a bioavailability of 7% in the liver (target organ), approximately 5-fold greater than the plasma bioavailability (B). Favourable liver uptake following oral administration is supported by similar bioavailability in plasma and kidney. Since the ASO is not active in rodents or dogs, we used a rat-specific GalNAc- Malat-1 ASO with the same chemistry to confirm target engagement. Intrajejunal administration resulted in ≥78% mRNA knockdown in the liver for single doses of 3-40 mg/kg. A monkey tolerability study of the PCSK9 ASO further supports oral feasibility with all tested doses (28-56 mg/day) significantly reducing LDL-C already after 7 days of daily oral dosing. Based on available animal and human data, and an assumption of 5% oral bioavailability in humans, a daily dose of 15 mg ([10, 20], 90% CI) in man is predicted to reduce PCSK9 in plasma by 80% at steady-state. This supports the development of the compound for subcutaneous and oral administration to treat dyslipidemia.

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