scholarly journals Optimization and Evaluation of Poly(lactide-co-glycolide) Nanoparticles for Enhanced Cellular Uptake and Efficacy of Paclitaxel in the Treatment of Head and Neck Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 828
Author(s):  
Mohamed Haider ◽  
Amr Elsherbeny ◽  
Jayalakshmi Jagal ◽  
Anna Hubatová-Vacková ◽  
Iman Saad Ahmed
Keyword(s):  
Cellular Uptake ◽  
Fold Increase ◽  
Systemic Circulation ◽  
Free Drug ◽  
Carcinoma Cells ◽  
Spherical Particles ◽  
In Vitro Drug Release ◽  
Formulation Parameters ◽  
Drug Solution

The particle size (PS) and encapsulation efficiency (EE%) of drug-loaded nanoparticles (NPs) may inhibit their cellular uptake and lead to possible leakage of the drug into the systemic circulation at the tumor site. In this work, ultra-high paclitaxel-loaded poly(lactide-co-glycolide) NPs (PTX-PLGA-NPs) with ultra-small sizes were prepared and optimized by adopting the principles of quality by design (QbD) approach. The optimized PTX-PLGA-NPs showed ultra-small spherical particles of about 53 nm with EE% exceeding 90%, a relatively low polydispersity index (PDI) of 0.221, an effective surface charge of −10.1 mV, and a 10-fold increase in the in vitro drug release over 72 h relative to free drug. The cellular viability of pharynx carcinoma cells decreased by almost 50% in 24 h following treatment with optimized PTX-PLGA-NPs, compared to only 20% from the free drug. The intracellular uptake of PTX-PLGA-NPs was highly favored, and the antitumor activity of PTX was remarkably improved with a reduction in its half maximal inhibitory concentration (IC50), by almost 50% relative to free drug solution. These results suggest that the optimal critical formulation parameters, guided by QbD principles, could produce PLGA-NPs with remarkably high EE% and ultra-small PS, resulting in enhanced cellular uptake and efficacy of PTX.

scholarly journals Nanocrystals of Fusidic Acid for Dual Enhancement of Dermal Delivery and Antibacterial Activity: In Vitro, Ex Vivo and In Vivo Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 199 ◽  
Author(s):  
Iman S. Ahmed ◽  
Osama S. Elnahas ◽  
Nouran H. Assar ◽  
Amany M. Gad ◽  
Rania El Hosary
Keyword(s):  
Fusidic Acid ◽  
Therapeutic Efficacy ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Fold Increase ◽  
Spherical Particles ◽  
Resistant Bacteria ◽  
Infection Model

With the alarming rise in incidence of antibiotic-resistant bacteria and the scarcity of newly developed antibiotics, it is imperative that we design more effective formulations for already marketed antimicrobial agents. Fusidic acid (FA), one of the most widely used antibiotics in the topical treatment of several skin and eye infections, suffers from poor water-solubility, sub-optimal therapeutic efficacy, and a significant rise in FA-resistant Staphylococcus aureus (FRSA). In this work, the physico-chemical characteristics of FA were modified by nanocrystallization and lyophilization to improve its therapeutic efficacy through the dermal route. FA-nanocrystals (NC) were prepared using a modified nanoprecipitation technique and the influence of several formulation/process variables on the prepared FA-NC characteristics were optimized using full factorial statistical design. The optimized FA-NC formulation was evaluated before and after lyophilization by several in-vitro, ex-vivo, and microbiological tests. Furthermore, the lyophilized FA-NC formulation was incorporated into a cream product and its topical antibacterial efficacy was assessed in vivo using a rat excision wound infection model. Surface morphology of optimized FA-NC showed spherical particles with a mean particle size of 115 nm, span value of 1.6 and zeta potential of −11.6 mV. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of FA following nanocrystallization and lyophilization. In-vitro results showed a 10-fold increase in the saturation solubility of FA-NC while ex-vivo skin permeation studies showed a 2-fold increase in FA dermal deposition from FA-NC compared to coarse FA. Microbiological studies revealed a 4-fofd decrease in the MIC against S. aureus and S. epidermidis from FA-NC cream compared to commercial Fucidin cream. In-vivo results showed that FA-NC cream improved FA distribution and enhanced bacterial exposure in the infected wound, resulting in increased therapeutic efficacy when compared to coarse FA marketed as Fucidin cream.

Linseed polysaccharides based nanoparticles for controlled delivery of docetaxel: Design, in vitro drug release and cellular uptake

2019 ◽  
Vol 49 ◽  
pp. 143-151 ◽  
Author(s):  
Muhammad Tahir Haseeb ◽  
Nisar Ul Khaliq ◽  
Soon Hong Yuk ◽  
Muhammad Ajaz Hussain ◽  
Sajid Bashir
Keyword(s):  
Drug Release ◽  
Cellular Uptake ◽  
Controlled Delivery ◽  
In Vitro Drug Release

Movement of Hydroxyurea Across Cell Membranes Is Mediated by Specific Solute Carrier (SLC) Transporters.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2575-2575
Author(s):  
Aisha L. Walker ◽  
Ryan M Franke ◽  
Alex Sparreboom ◽  
Russell E. Ware
Keyword(s):  
Vector Control ◽  
Cellular Uptake ◽  
Organic Cation ◽  
Organic Anion ◽  
Fold Increase ◽  
The Body ◽  
Transcellular Transport ◽  
Slc Transporters ◽  
Solute Carrier

Abstract Abstract 2575 Poster Board II-552 Background: Hydroxyurea is the only FDA-approved drug for the treatment of sickle cell anemia (SCA) in adults. Hydroxyurea increases fetal hemoglobin, decreases hospitalizations and painful events, and reduces mortality. With an oral bioavailability of > 90%, hydroxyurea is rapidly absorbed and distributed throughout the body. Though hydroxyurea has proven to be effective in treating SCA, there is considerable inter-patient variability observed in the pharmacokinetics and pharmacodynamics of hydroxyurea. Currently, mechanisms involved in the absorption, distribution, and elimination of hydroxyurea remain unclear. Recently, key transmembrane proteins have been identified as drug transporters due to their ability to move a variety of xenobiotic substances across cell membranes. Drug transporters are widely distributed throughout the body, and most are specific to certain substrates. Solute carrier (SLC) transporters in particular have been to shown to significantly impact drug pharmacokinetics by influencing the absorption, distribution, and elimination of specific drugs. The present study was designed to identify SLC transporters that may influence the absorption, distribution, and/or elimination of hydroxyurea in patients with SCA. Methods: In vitro studies using an equilibrium dialysis plate were performed to determine the amount of hydroxyurea that binds to human serum proteins. Transporter-mediated cellular uptake of hydroxyurea was determined in vitro by measuring [14C]-hydroxyurea accumulation in HEK293 cells and oocytes that overexpress organic anion transporters (OAT1-3), organic cation transporters (OCT1-3), organic cation/carnitine transporters (OCTN1-2), organic anion transporting polypeptides (OATP1A2/OATP1B1/OATP1B3), or vector control. LLC-PK1 cells that overexpress urea transporters A or B (UTA/UTB) were used to determine UTA/UTB mediated transcellular transport of hydroxyurea in transwell plates. The transport of [14C]-hydroxyurea from apical to basal or from basal to apical compartments was measured for the UTA/UTB overexpressing cells and compared to vector control. UTA and UTB mRNA expression was measured by real-time PCR of cDNA obtained from human tissue samples. Results: Protein binding assays showed that >76% of [14C]-hydroxyurea remained unbound to proteins in human serum containing hydroxyurea at concentrations ranging from 1.5μM to 500μM. The fraction of unbound hydroxyurea was similar using serum obtained from pediatric patients with SCA. In uptake studies, [14C]-hydroxyurea was a potent substrate for OATP1B3 with an approximately 2-fold increase in drug accumulation compared to control (p<0.001). In contrast, hydroxyurea was found to be a weak substrate for OCTN1, OCTN2, OATP1A2, and OATP1B1 with only a 1.3-fold increase in drug accumulation compared to control (p<0.04). Transcellular transport of hydroxyurea was increased 3- and 2-fold by UTA and UTB, respectively, compared to vector control demonstrating hydroxyurea to be a potent substrate for these transporters as well (p<0.02). When the urea transporter inhibitor dimethylurea was added, hydroxyurea transport by UTA and UTB-expressing cells was decreased to levels observed with the vector control. In real-time PCR assays, kidney, muscle, and small intestine were among human tissues with high expression of UTA mRNA, while prostate, brain, and bone marrow had high levels of UTB mRNA expression. Conclusion: Cellular uptake of hydroxyurea is mediated by active transport via specific SLC transporters OATP1B3, UTA and UTB, which are expressed in liver, kidney, brain, intestine, and blood cells. Studies to further characterize hydroxyurea transporters should improve our understanding of the pharmacokinetic and pharmacodynamic profiles of hydroxyurea used in clinical practice for patients with SCA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Development of Novel Galactosylated PLGA Nanoparticles for Hepatocyte Targeting Using Molecular Modelling

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 94 ◽  
Author(s):  
Cláudia D. Raposo ◽  
Rita Costa ◽  
Krasimira T. Petrova ◽  
Catarina Brito ◽  
Marcus T. Scotti ◽  
...  
Keyword(s):  
Plga Nanoparticles ◽  
Carcinoma Cells ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
In Vitro Drug Release ◽  
Promising Tool ◽  
Three Phase ◽  
Cellular Carcinoma ◽  
Drug Encapsulation Efficiency

Doxorubicin-loaded PLGA nanoparticles conjugated with a new galactose-based ligand for the specific recognition by human hepatoma cellular carcinoma cells (Hep G2) were successfully produced. The new targeting compound was selected using molecular docking combined with quantum chemical calculations for modelling and comparing molecular interactions among the H1 subunit of the asialoglycoprotein receptor containing the carbohydrate recognition domain and the ligand. The ligand, bis(1-O-ethyl-β-D-galactopyranosyl)amine, was synthetized, characterized, and subsequently linked to PLGA. Unloaded (PLGA-di-GAL NP) and doxorubicin-loaded (DOX-PLGA-di-GAL NP) nanoparticles were prepared using an emulsion method and characterized. The produced DOX-PLGA-di-GAL NP are spherical in shape with a size of 258 ± 47 nm, a zeta potential of −62.3 mV, and a drug encapsulation efficiency of 83%. The in vitro drug release results obtained show a three-phase release profile. In vitro cell studies confirmed the interaction between Hep G2 cells and PLGA-di-GAL NP. Cell cytotoxicity tests showed that unloaded NP are nontoxic and that DOX-PLGA-di-GAL NP caused a decrease of around 80% in cellular viability. The strategy used in this work to design new targeting compounds represents a promising tool to develop effective hepatocyte targeting drug delivery systems and can be applied to other tissues/organs.

Cellular Uptake and In Vitro Drug Release Studies on Paclitaxel-Loaded Poly(caprolactone)-Grafted Dextran Copolymeric Nanoparticles

2009 ◽  
Vol 5 (1-4) ◽  
pp. 42-49 ◽  
Author(s):  
P. Prabu ◽  
Atul A. Chaudhari ◽  
J. A. Ko ◽  
N. Dharmaraj ◽  
S. Y. Park ◽  
...  
Keyword(s):  
Drug Release ◽  
Cellular Uptake ◽  
In Vitro Drug Release ◽  
Release Studies ◽  
Poly Caprolactone

Cellular Uptake of Carotenoid-Loaded Oil-in-Water Emulsions in Colon Carcinoma Cells in Vitro

2006 ◽  
Vol 54 (25) ◽  
pp. 9366-9369 ◽  
Author(s):  
Henelyta S. Ribeiro ◽  
José M. M. Guerrero ◽  
Karlis Briviba ◽  
Gerhard Rechkemmer ◽  
Heike P. Schuchmann ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Cellular Uptake ◽  
Carcinoma Cells ◽  
Colon Carcinoma Cells ◽  
Oil In Water

scholarly journals PRONIOSOMES: A VESICULAR DRUG DELIVERY SYSTEM

2021 ◽  
pp. 32-36
Author(s):  
SARITHA M. ◽  
SATYA PRAKASH PANDA ◽  
SRAVANI BUDDHA ◽  
P. V. KAMALA KUMARI ◽  
Y. SRINIVASA RAO
Keyword(s):  
Drug Delivery ◽  
Aqueous Media ◽  
Physical Stability ◽  
Entrapment Efficiency ◽  
Systemic Circulation ◽  
Vital Role ◽  
Water Soluble ◽  
In Vitro Drug Release ◽  
Vesicular Carriers

In the development of new dosage forms, drug delivery using nanotechnology is playing a vital role. Vesicular drug delivery systems have gained wide attention in the field of nanotechnology, such as niosomes, liposomes and proniosomes. Among the vesicular carriers, proniosomes are superior. Proniosomes are water-soluble carrier particles that are coated with surfactant so these are dry formulations. They are rehydrated to use on agitation in hot aqueous media within minutes to form niosomal dispersion immediately. Both hydrophilic and lipophilic drugscan be incorporated into these proteasomes. The physical stability problems of niosomes like aggregation, fusion and leaking are minimized in proniosomes, routes, such as oral, parenteral, dermal and transdermal, ocular, oral mucosal, vaginal, pulmonary, and intranasal. Proniosomes prolong the existence of the drug in the systemic circulation and finally reduces toxicity. This review focuses on different aspects of proniosomes such as preparation, characterization, in vitro drug release, entrapment efficiency, applications in the present scenario in the market and future trends.

scholarly journals Copolymeric Micelles Overcome the Oral Delivery Challenges of Amphotericin B

2020 ◽  
Vol 13 (6) ◽  
pp. 121
Author(s):  
Pataranapa Nimtrakul ◽  
Desmond B. Williams ◽  
Waree Tiyaboonchai ◽  
Clive A. Prestidge
Keyword(s):  
Amphotericin B ◽  
Oral Delivery ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Aqueous Solubility ◽  
Fold Increase ◽  
Free Drug ◽  
Absorption Studies

Classified as a Biopharmaceutical Classification System (BCS) class IV drug, amphotericin B (AmB) has low aqueous solubility and low permeability leading to low oral bioavailability. To improve these limitations, this study investigated the potential of AmB-loaded polymeric micelles (AmB-PM) to increase intestinal absorption. AmB-PM were prepared with polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol copolymer (Soluplus®) as a polymeric carrier and used a modified solvent diffusion and microfluidics (NanoAssemblr®) method. AmB-PM have a mean particle size of ~80 nm and are mono-disperse with a polydispersity index <0.2. The entrapment efficiency of AmB was up to 95% and achieved with a high drug loading up to ~20% (w/w) with a total amount of incorporated drug of 1.08 ± 0.01 mg/mL. Importantly, compared to free drug, AmB-PM protected AmB from degradation in an acidic (simulated gastric) environment. Viability studies in Caco-2 cells confirmed the safety/low toxicity of AmB-PM. In vitro cellular absorption studies confirmed that AmB-PM increased AmB uptake in Caco-2 cells 6-fold more than free AmB (i.e., 25% compared with 4% within 30 min). Furthermore, the permeability of AmB across Caco-2 monolayers was significantly faster (2-fold) and more pronounced for AmB-PM in comparison to free drug (3.5-fold increase). Thus, the developed AmB-PM show promise as a novel oral delivery system for AmB and justifies further investigation.

scholarly journals DEVELOPMENT OF ZOLMITRIPTAN MOUTH DISSOLVING FILMS: FORMULATION VARIABLES, MECHANICAL PROPERTIES, AND IN VITRO DRUG RELEASE STUDIES

2019 ◽  
pp. 273-279
Author(s):  
SUDHIR MADDELA ◽  
BUCHI N. NALLURI
Keyword(s):  
Tensile Strength ◽  
Drug Release ◽  
Film Thickness ◽  
Fold Increase ◽  
Release Rates ◽  
In Vitro Drug Release ◽  
Release Studies ◽  
Formulation Variables ◽  
Pvp K30

Objective: The objective of the present investigation is to prepare zolmitriptan (ZOL) mouth dissolving films (MDFs) and to investigate the influence of formulation variables on physicomechanical, chemical, and drug release properties of the prepared MDFs. Methods: The MDFs were prepared by solvent casting technique using wet film applicator. The impact of hydroxypropyl methylcellulose of different viscosity grades (hydroxy propyl methyl cellulose [HPMC] E3, E5, and E15), plasticizers (glycerol and polyethylene glycol [PEG]-400), and solubilizing agents (polyvinyl pyrrolidone [PVP K30] and sodium lauryl sulfate [SLS]) on physicomechanical, chemical, and drug release properties were evaluated. The MDFs were also characterized by Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry studies. Results: The MDFs prepared were transparent and smooth and showed no recrystallization. The tensile strength of the MDFs increased significantly with an increase in polymer viscosities, and about a 2.63-fold increase in tensile strength was observed for HPMC E15 MDFs compared to E3, whereas an increase in film thickness resulted in brittle MDFs with low tensile strength. Similar results were observed with percent elongation and folding endurance of the MDFs. In vitro, drug release studies indicate that higher film thickness and polymer viscosities delayed the MDF disintegration and, in turn, the ZOL release. Addition of PVP K30 and SLS to HPMC E3 formulations resulted in 1.66- and 1.53-fold increase in ZOL release rates. Conclusion: Overall, F7 formulation showed quicker disintegration (within 11 s) and ZOL release rates (within 180 s) along with good physicomechanical properties. These results indicated that the disintegration and drug release of ZOL can be enhanced to a greater extent by optimizing formulation variables in MDFs.

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