Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles

In this study, we developed a novel solid lipid nanoparticle (SLN) formulation for drug delivery of small hydrophilic cargos to the retina. The new formulation, based on a gel core and composite shell, allowed up to two-fold increase in the encapsulation efficiency. The type of hydrophobic polyester used in the composite shell mixture affected the particle surface charge, colloidal stability, and cell internalization profile. We validated SLNs as a drug delivery system by performing the encapsulation of a hydrophilic neuroprotective cyclic guanosine monophosphate analog, previously demonstrated to hold retinoprotective properties, and the best formulation resulted in particles with a size of ±250 nm, anionic charge > −20 mV, and an encapsulation efficiency of ±60%, criteria that are suitable for retinal delivery. In vitro studies using the ARPE-19 and 661W retinal cell lines revealed the relatively low toxicity of SLNs, even when a high particle concentration was used. More importantly, SLN could be taken up by the cells and the release of the hydrophilic cargo in the cytoplasm was visually demonstrated. These findings suggest that the newly developed SLN with a gel core and composite polymer/lipid shell holds all the characteristics suitable for the drug delivery of small hydrophilic active molecules into retinal cells.

Download Full-text

Soft Cationic Nanoparticles for Drug Delivery: Production and Cytotoxicity of Solid Lipid Nanoparticles (SLNs)

Applied Sciences ◽

10.3390/app9204438 ◽

2019 ◽

Vol 9 (20) ◽

pp. 4438 ◽

Cited By ~ 14

Author(s):

Amélia Silva ◽

Carlos Martins-Gomes ◽

Tiago Coutinho ◽

Joana Fangueiro ◽

Elena Sanchez-Lopez ◽

...

Keyword(s):

Drug Delivery ◽

Surface Properties ◽

Cell Lines ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Cationic Lipids ◽

Solid Lipid ◽

Mcf 7

The surface properties of nanoparticles have decisive influence on their interaction with biological barriers (i.e., living cells), being the concentration and type of surfactant factors to have into account. As a result of different molecular structure, charge, and degree of lipophilicity, different surfactants may interact differently with the cell membrane exhibiting different degrees of cytotoxicity. In this work, the cytotoxicity of two cationic solid lipid nanoparticles (SLNs), differing in the cationic lipids used as surfactants CTAB (cetyltrimethylammonium bromide) or DDAB (dimethyldioctadecylammonium bromide), referred as CTAB-SLNs and DDAB-SLNs, respectively, was assessed against five different human cell lines (Caco-2, HepG2, MCF-7, SV-80, and Y-79). Results showed that the cationic lipids used in SLN production highly influenced the cytotoxic profile of the particles, with CTAB-SLNs being highly cytotoxic even at low concentrations (IC50 < 10 µg/mL, expressed as CTAB amount). DDAB-SLNs produced much lower cytotoxicity, even at longer exposure time (IC50 from 284.06 ± 17.01 µg/mL (SV-80) to 869.88 ± 62.45 µg/mL (MCF-7), at 48 h). To the best of our knowledge, this is the first report that compares the cytotoxic profile of CTAB-SLNs and DDAB-SLNs based on the concentration and time of exposure, using different cell lines. In conclusion, the choice of the right surfactant for biological applications influences the biocompatibility of the nanoparticles. Regardless the type of drug delivery system, not only the cytotoxicity of the drug-loaded nanoparticles should be assessed, but also the blank (non-loaded) nanoparticles as their surface properties play a decisive role both in vitro and in vivo.

Download Full-text

Solid Lipid Nanoparticles for Dibucaine Sustained Release

Pharmaceutics ◽

10.3390/pharmaceutics10040231 ◽

2018 ◽

Vol 10 (4) ◽

pp. 231 ◽

Cited By ~ 8

Author(s):

Raquel de M. Barbosa ◽

Ligia Ribeiro ◽

Bruna Casadei ◽

Camila da Silva ◽

Viviane Queiróz ◽

...

Keyword(s):

Solid Lipid Nanoparticles ◽

Encapsulation Efficiency ◽

Colloidal Stability ◽

Lipid Nanoparticles ◽

In Vitro Cytotoxicity ◽

Tail Flick ◽

Release Kinetic ◽

Solid Lipid

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72–89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.

Download Full-text

Composite solid lipid nanoparticles with hydrogel core for delivering small hydrophilic molecules to the retina: an in vitro study using ARPE-19 and 661W cells

10.1101/2021.05.24.445543 ◽

2021 ◽

Author(s):

Erico Himawan ◽

Li Huang ◽

Soumaya Belhadj ◽

Raul Oswaldo Perez Garcia ◽

François Paquet-Durand ◽

...

Keyword(s):

Delivery System ◽

Encapsulation Efficiency ◽

Fluorescent Dyes ◽

Composite Shell ◽

Pigment Epithelium ◽

Retinal Pigment ◽

In Vitro Study ◽

Solid Lipid ◽

Drug Molecules

Delivering small hydrophilic drug molecules to the retina is a challenging task in ophthalmology. A solid lipid nanoparticle (SLP) with a composite shell and hydrogel core as delivery system of a hydrophilic cargo to retinal cells has been developed in this work to meet the challenge. The composite shell formed by lipid and hydrophobic polyesters improves polydispersity while the hydrogel core enhances the encapsulation efficiency when compared to conventional SLP. In vitro studies tracking internalization and release of hydrophilic fluorescent dyes in retinal pigment epithelium and photoreceptor cell lines, showed a successful uptake and release of the hydrophilic cargo inside the cells. Validation of SLP encapsulation capability using a neuroprotective cGMP analogue resulted in a SLP size < 250 nm, negative surface charge > -20 mV, and encapsulation efficiency value of 60%. This formulation shows a potential to be applied as ocular drug delivery system and may open new perspectives for developing a treatment for retinal diseases.

Download Full-text

Development of Solid Lipid Nanoparticles of Lamivudine for Brain Targeting

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v1i1.8837 ◽

2009 ◽

Vol 1 (1) ◽

Cited By ~ 1

Author(s):

Pravin Patil ◽

Anil Sharma ◽

Subhash Dadarwal ◽

Vijay Sharma

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Solid Lipid Nanoparticles ◽

Rotation Speed ◽

Lipid Nanoparticles ◽

Brain Targeting ◽

Brain Penetration ◽

Solid Lipid ◽

Diffusion Technique

The objective of present investigation was to enhance brain penetration of Lamivudine, one of the most widely used drugs for the treatment of AIDS. This was achieved through incorporating the drug into solid lipid nanoparticles (SLN) prepared by using emulsion solvent diffusion technique. The formulations were characterized for surface morphology, size and size distribution, percent drug entrapment and drug release. The optimum rotation speed, resulting into better drug entrapment and percent yield, was in the range of 1000-1250 r/min. In vitro cumulative % drug release from optimized SLN formulation was found 40-50 % in PBS (pH-7.4) and SGF (pH-1.2) respectively for 10 h. After 24 h more than 65 % of the drug was released from all formulations in both mediums meeting the requirement for drug delivery for prolong period of time.

Download Full-text

Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

Cancer Nanotechnology ◽

10.1186/s12645-021-00085-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Farnaz Dabbagh Moghaddam ◽

Iman Akbarzadeh ◽

Ehsan Marzbankia ◽

Mahsa Farid ◽

Leila khaledi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Treatment ◽

Cell Lines ◽

Encapsulation Efficiency ◽

Inbred Mice ◽

Breast Cancer Treatment ◽

Anticancer Effect ◽

Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

Download Full-text

Safety and Efficacy of Suicide Gene Therapy with Adenosine Deaminase 5-Fluorocytosine Silmutaneously in in Vitro Cultures of Melanoma and Retinal Cell Lines

Journal of Cancer ◽

10.7150/jca.9147 ◽

2014 ◽

Vol 5 (5) ◽

pp. 368-381 ◽

Cited By ~ 3

Author(s):

Antonios Sakkas ◽

Paul Zarogoulidis ◽

Kalliopi Domvri ◽

Wolfgang Hohenforst-Schmidt ◽

Dimitris Bougiouklis ◽

...

Keyword(s):

Gene Therapy ◽

Adenosine Deaminase ◽

Cell Lines ◽

Suicide Gene ◽

In Vitro Cultures ◽

Suicide Gene Therapy ◽

Retinal Cell ◽

Safety And Efficacy

Download Full-text

Triggered drug release from hybrid thermoresponsive nanoparticles using near infrared light

Nanomedicine ◽

10.2217/nnm-2019-0270 ◽

2020 ◽

Vol 15 (3) ◽

pp. 219-234 ◽

Cited By ~ 1

Author(s):

Isabel Ortiz de Solorzano ◽

Martin Prieto ◽

Gracia Mendoza ◽

Victor Sebastian ◽

Manuel Arruebo

Keyword(s):

Drug Delivery ◽

Gold Nanoparticles ◽

Colloidal Stability ◽

Near Infrared ◽

Chemical Characterization ◽

Infrared Light ◽

Galvanic Replacement ◽

Heating Efficiency ◽

Hollow Gold Nanoparticles

Aim: Developing hybrid poly(N-isopropylacrylamide)-based nanogels decorated with plasmonic hollow gold nanoparticles for on-demand drug delivery and their physico-chemical characterization, bupivacaine loading and release ability upon light irradiation, and in vitro cell viability. Materials & methods: Hollow gold nanoparticles were prepared by galvanic replacement reaction; poly(N-isopropylacrylamide)-based nanogels were synthesized via precipitation polymerization and their electrostatic coupling was accomplished using poly(allylamine hydrochloride) as cationic polyelectrolyte linker. Results & conclusion: Colloidal stability of the resulted hybrid nanovectors was demonstrated under physiological conditions together with their fast response and excellent heating efficiency after light stimulation, indicating their potential use as triggered drug-delivery vectors. Moreover, their influence on cell metabolism and cell cycle under subcytotoxic doses were studied showing excellent cytocompatibility.

Download Full-text

Emulsion electrospun polylactic acid/Apocynum venetum nanocellulose nanofiber membranes with controlled sea buckthorn extract release as a drug delivery system

Textile Research Journal ◽

10.1177/0040517520970171 ◽

2020 ◽

pp. 004051752097017

Author(s):

Lu Wang ◽

Chenmeizi Wang ◽

Ling Wang ◽

Qingle Zhang ◽

Ying Wang ◽

...

Keyword(s):

Drug Delivery ◽

Polylactic Acid ◽

Encapsulation Efficiency ◽

Sea Buckthorn ◽

Burst Release ◽

Nanofiber Membrane ◽

Apocynum Venetum ◽

Nanofiber Membranes ◽

Sheath Structure

Prolonging the duration of drug action and reducing toxicity play a vital role in wound administration as they reduce the chance of infection and decrease complications and cost. This study reports the natural antioxidant procyanidins extracted from sea buckthorn (SBT) and laboratory-manufactured Apocynum venetum cellulose nanofiber as core drugs. The sustained-release nanofiber membrane was prepared by electrospinning on polylactic acid/polyvinyl pyrrolidone nanofibers. High-performance liquid chromatography-mass spectrometry was used to identify the phenolic compounds in SBT extracts and confirmed the presence of procyanidins with a content of 0.0345 mg/g. The nanofiber membrane was characterized through transmission electron microscopy, encapsulation efficiency, in vitro drug-release study and antioxidant assay. The results indicated that the extracted procyanidins were successfully encapsulated in the core–sheath structure nanofibers, and the encapsulation efficiency of nanofiber membranes reached 83.84%. In vitro measurements of the delivery showed this core–sheath structure could significantly alleviate the drug burst release, which is followed by a linear and smooth release within 30 hours. Further tests showed that the removal efficiency of 2,2-diphenyl-1-picrylhydrazyl reached 88.62%, indicating that the membranes had high antioxidant activity. This work implies that the combination of Apocynum venetum nanocellulose and emulsion electrospun fibers has promising potential applications in tissue engineering or drug delivery.

Download Full-text