Modified Nanoprecipitation Method Research Articles

QbD-Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture.

Biomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)-loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa-nHA-GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box-Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269nm, 0.18, -20.5mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine-B loaded nHA-GLT NPs demonstrates considerably higher cellular uptake by the murine-derived macrophages than free rhodamine-B solution. In vitro, cell-based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD-based approach has successfully led to the development of Tofa-nHA-GLT NPs with the potential to target inflamed arthritic joint.

Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA.

Vectorized small interfering RNAs (siRNAs) are widely used to induce gene silencing. Among the delivery systems used, lipid-based particles are the most effective. Our objective was the development of novel lipid-polymer hybrid nanoparticles, from lipoplexes (complexes of cationic lipid and siRNAs), and poly (lactic-co-glycolic acid) (PLGA), using a simple modified nanoprecipitation method. Due to their morphology, we called these hybrid nanoparticles Spheroplexes. We elucidated their structure using several physico-chemical techniques and showed that they are composed of a hydrophobic PLGA matrix, surrounded by a lipid envelope adopting a lamellar structure, in which the siRNA is complexed, and they retain surface characteristics identical to the starting nanoparticles, i.e. lipoplexes siRNA. We analyzed the composition of the particle population and determined the final percentage of spheroplexes within this population, 80 to 85% depending on the preparation conditions, using fluorescent markers and the ability of flow cytometry to detect nanometric particles (approximately 200nm). Finally, we showed that spheroplexes are very stable particles and more efficient than siRNA lipoplexes for the delivery of siRNA to cultured cells. We administered spheroplexes contain siRNAs targeting TNF-α to mice with ulcerative colitis induced by dextran sulfate and our results indicate a disease regression effect with a response probably mediated by their uptake by macrophages / monocytes at the level of lamina propria of the colon. The efficacy of decreased level of TNF-α in vivo seemed to be an association of spheroplexes polymer-lipid composition and the specific siRNA. These results demonstrate that spheroplexes are a promising hybrid nanoparticle for the oral delivery of siRNA to the colon.

Evaluation of nanoparticles with 5-fluorouracil and chloroquine on Acanthamoeba castellanii activity

Acanthamoeba is opportunistic pathogens that cause vision-threatening Acanthamoeba keratitis (AK). Previous studies proposed the use of chloroquine (CQ) and 5-fluorouracil (5FU) as anti-Acanthamoeba agents. The objective of this study was to determine the benefit of using 5FU and CQ nanoparticles (NP) formulations against A. castellanii that belonging to the T4 genotype and evaluate their anti-Acanthamoebic characteristic. Triplicate batches of 5FU nanoparticles (5FU-NP) were synthesized by using a modified nanoprecipitation method, while CQ nanoparticles (CQ-NP) synthesized using a modified double emulsion method. The synthesized nanoparticles were subjected to biological assays to investigate their amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects against A. castellanii, as well as cell cytotoxicity. Cytotoxicity assays were performed using human keratinocyte cells (HaCaT) to determine the effect of CQ and 5FU nanoformulations on host cells. 5FU-NP with a concentration of 60 µM showed significant inhibition to amoeba binding into human cell lines and remarkable prevention mainly during the encystation stage. Moreover, 5FU-NP resulted in less cytotoxicity and pathogenicity when compared with the free 5FU. On the other hand, CQ and CQ-NP, at the same concentration, showed poor inhibition to amoeba binding into human cells and insignificant prevention to encystation stage. Moderate human cells damage was resulted following their treatment with CQ and CQ-NP. In conclusion, 5FU may have the potential as an antiamoebic agent against Acanthamoeba spp. preferably as a nanoformulation to enhance its activity and reduce its cytoxicity.

Abstract 231: Monocyte-mimicking Nanoparticles For Atherosclerosis-targeted Therapy

Atherosclerosis, characterized by plaque buildup in arteries, is a major cause of cardiovascular mortality globally. Despite advances in diagnostics and interventions over the past few decades, the treatment options and outcomes remain far less than optimal. Nanotechnology has demonstrated emerging success in clinical settings; however, a potent targeted nanotherapeutic for atherosclerosis remains underdeveloped. In this study, we designed a new class of nanocarriers mimicking circulating monocyte features to enhance the site-specific delivery of theranostic agents for atherosclerosis. We first synthesized polymeric cores encapsulating a fluorescent payload with a modified nanoprecipitation method and cloaked the polymeric cores (NPs) with the plasma membrane fraction isolated from mouse monocytes. Our characterization results verified that NP cores are covered with a uniform lipid layer and that the resulting monocyte-mimicking nanoparticles (MNPs) retain the membrane proteins on their surface and have a similar value of zeta potential as monocytes. Both MNPs and NPs did not exhibit any hemotoxicity in vitro ; however, when incubated with cultured human vascular endothelial cells (ECs), MNPs showed a significantly higher uptake efficiency by ECs than NPs. Moreover, our in vivo studies with ApoE-knockout mice indicates that MNPs accumulated only in the atherosclerotic arteries but no other areas of the vasculature when administered intravenously. To summarize, our findings strongly support that monocyte membrane cloaking facilitates the nanoparticle attachment to atherosclerotic regions and enhances the entry of nanoparticles into the inflammatory endothelium in the arteries, suggesting that MNPs would serve as an excellent delivery strategy for targeted atherosclerosis therapy.

In vitro & in vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for baclofen and lamotrigine for neuropathic pain management

Aim Baclofen and Lamotrigine via PLGA nanoparticles were developed for nose-to-brain delivery for the treatment of Neuropathic pain. Methods Nanoparticles were prepared using the modified nano-precipitation method. The prepared NPs were characterised and further in vitro and in vivo studies were performed. Results The Bcf-Ltg-PLGA-NPs were ∼177.7 nm with >75%(w/w) drugs encapsulated. In vitro dissolution studies suggested zero-order release profiles following the Korsmeyer-Peppas model. In vitro cytotoxicity and staining studies on mammalian cells showed dose dependant cytotoxicity where nanoparticles were significantly less toxic (>95% cell-viability). ELISA studies on RAW-macrophages showed Bcf-Ltg-PLGA-NPs as a potential pro-inflammatory-cytokines inhibitor. In vivo gamma-scintigraphy studies on rats showed intra-nasal administration of 99mTc-Bcf-Ltg-PLGA-NPs showed C max 3.6%/g at T max = 1.5h with DTE% as 191.23% and DTP% = 38.61% in brain. Pharmacodynamics evaluations on C57BL/6J mice showed a significant reduction in licks/bites during inflammation-induced phase II pain. Conclusion The findings concluded that the combination of these drugs into a single nanoparticle-based formulation has potential for pain management.

Tunable self‐assembled stereocomplexed‐polylactic acid nanoparticles as a drug carrier

AbstractIn this study, a model hydrophilic drug (porphyrin) was encapsulated within hydrophobic polylactic acid (PLA) nanoparticles (NPs) with different crystallinity and the relevant release behaviors were investigated. The crystalline modification was done using a modified nanoprecipitation method, where homo and stereocomplexed PLA NPs with different average diameters based on varying polymer concentrations and solvent/nonsolvent ratios (S/N) were prepared. Entrapment efficiency and drug release of sterocomplexed‐PLA NPs were compared with neat poly(l‐lactic acid) (PLLA) NPs. Furthermore, to get the more sustained release, porphyrin‐loaded NPs were immobilized within electrospun poly(d,l‐lactide‐co‐glycolide (PLGA) nanofibers (NFs). Outcomes revealed that solution concentration and solvent/nonsolvent ratio play significant roles in the formation of homo and stereocomplexed NPs. On the other hand, it was found that the formation of stereocrystals did not significantly affect the size and morphology of NPs compared with neat NPs. With regard to the entrapment efficiency and drug content, stereocomplexd‐PLA NPs behave relatively the same as neat PLLA NPs while the more sustained release was observed for stereocomplexed NPs. Also, it was observed that electrospinning of PLGA solution loaded by NPs led to the uniform distribution of NPs into PLGA fibers. Encapsulating the drug‐loaded NPs into nanofibers decreased the rate of drug release by 50% after 24 h, compared with direct loading of drug into PLGA NFs. We conclude that it is possible to tune the entrapment efficiency and modify the release rate of the drug by giving small changes in the process parameters without altering the physical properties of the original drug substance and polymer.

Donepezil loaded PLGA Nanoparticles, from Modified Nano-Precipitation, an Advanced Drug Delivery System to treat Alzheimer Disease

In present works we synthesized Donepezil loaded PLGA nanoparticles (NPs). The approach of our research group was to prove the improvement of drug transport through the Blood Brain Barrier when donepezil was loaded with PLGA. It promoted the uptake of drug into brain endothelium compared with the free drug and play a significant role in the treatment of Alzheimer’s disease (AD). The NPs were synthesized by modified Nano precipitation method. These synthesized polymeric nanoparticles were characterized for particle size, Polydispersity index (PDI) and Zeta potential. The average size and PDI of drug loaded polymeric nanoparticle for preferred formulation were found to be 40.8 nm and 0.188 respectively. The Entrapment Efficiency was 74% and Process yield was 78%. The electron microscopic images of polymeric nanoparticles suggested that the particles were spherical in shape. The pharmacokinetics showed that the release behavior of NPs were very much similar to sustained release and follow Hixson Crowell model.

Photodynamic antimicrobial chemotherapy through photosensitizers loaded poly-l-glycolic acid on Candida albicans in denture lining material: Release, biological and hardness study.

The aim of this in-vitro study was to formulate poly-l-glycolic acid nanoparticles loaded with methylene blue (PLGA-MB) and to characterize their physicochemical features, photosensitizer-release kinetics and antimicrobial efficacy against Candida albicans (C. albicans) after incorporating in polymethyl methacrylate (PMMA) denture lining materials. MB-PLGA nanoparticles were synthesized according to the modified nanoprecipitation method. The morphological characterization of the nanoparticles was studied under scanning and transmission electron microscope. Particle size, surface charge, polydispersity index (PDI) and MB release were evaluated. The effect of 660 nm semiconductor AlGaInP diode laser on C. albicans was studied in vitro. The PMMA was weighed and PLGA free and PLGA-MB were added in the lining material according to the weight percentage as 2.0 wt.% and 5.0 wt.% and tested for the diameter of the inhibition zones of C. albicans growth and shore A hardness. Homogenous spherical nanoparticles with round morphology with size ranging between 60-80 nm were observed while PLGA-MB were seen to have irregular structure within the nanoparticle under TEM. PLGA-Free was larger in size than the loaded PLGA (∼62 nm) that evidenced reduction in size by adding the MB photosensitizer. PDI recordings reduced from 0.198 for the PLGA-Free nanoparticles to 0.164 for the PLGA-MB nanoparticles. The entrapment efficiency of MB inside PLGA showed an average percentage of ∼75 % uptake that resulted in the overall loading of ∼15 %. An overall inhibition of 78 %, 41 % and 28 % of C. albicans growth was seen with a concentration of 0.1, 0.5 and 1.0 μg/mL, respectively. The application of PLGA nanoparticles loaded with MB evidenced >75 % of C. albicans. MB incorporation did not lead to a clinically relevant change on shore A hardness. PLGA loaded with MB is believed to have promising target therapy against C. albicans in denture soft lining materials in terms of PACT in vitro. The synergistic association between PLGA and MB proved enhanced antifungal activity. PLGA-MB could be an important tool in nanobiotechnology and photodynamic therapy for novel formulations with higher antimicrobial efficacy and improved drug delivery from denture soft lining materials.

Preparation of a new fluorescence nanochemosensor for Sn(II) ions by a modified nanoprecipitation method

A new dialdehyde was designed and synthesized containing naphthalene groups, and then its macrocycle was prepared with 1,4-diaminobuthan. A modified nanoprecipitation method has been reported for the preparation of the nanoparticles. In this method, to obtain nanoparticles with small particle sizes, the nucleation rate was increased with decreasing of the mixing time. The organic nanoparticles were used for turn-off fluorescence response of low concentration of Sn2+ ions over cations such as Cs+, K+, Na+, Ba2+, Ca2+, Mg2+, Al3+, Pb2+, Zn2+, Cu2+, Ni2+, Co2+, Fe2+, Mn2+, Ag+, Cd2+, and Hg2+ and ions in aqueous buffer solution. The limit of detection was 5.4 nM.

Preparation and evaluation of schisandrin B-loaded F127 modified lipid-polymer nanoparticles for inhibition of breast cancer lung metastasis

In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) μg·L~(-1),(1 121.34±91.65) μg·L~(-1) and(2 951.91±360.53) μg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-β1(TGF-β1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.

Surface modification of PLGA nanoparticles with chitosan or Eudragit® RS 100: Characterization, prolonged release, cytotoxicity, and enhanced antimicrobial activity

Cefpodoxime proxetil (CEF) is a third-generation cephalosporin that is situated in BCS Class II with poor oral bioavailability. In current work, poly(lactic-co-glycolide) (PLGA) nanoparticles (NPs) with chitosan (CS)/Eudragit® RS 100 (ERS 100) were designed to be used as efficient and prolonged released antimicrobial drug delivery systems by modified nanoprecipitation method. The rational for this approach is to bring a new aspect to antimicrobial treatment with modification of CEF loaded PLGA NPs with CS/ERS 100 by means of smaller particle size (PS), cationic surface, biocompatible nature, prolonged release, and enhanced antimicrobial activity. The PS of CEF loaded NPs were between 181 and 382 nm. The zeta potential of NPs was achieved cationic character with the modification of NPs with CS/ERS 100. EE% values ranged from 36% to 64%. The surface modification and structures of NPs were confirmed with solid state analyses (DSC, FT-IR and 1H NMR). In vitro release profiles of NPs demonstrated extended release pattern which followed Peppas-Sahlin model. The safety and biocompatibility of NPs with higher cell viability values than CEF on CCD-19-Lu cell line. Antimicrobial efficacy of the NPs was analyzed against Staphylococcus aureus and Escherichia Coli by microdilution method. ERS 100 modified NPs were more effective on bacterial cells (4–8 fold) than CS modified and unmodified PLGA NPs both two organisms. Moreover, all NPs designed exhibited enhanced antimicrobial activity compared to free CEF. These findings indicate that surface modification with CS/ERS 100 were significantly effective on NPs characteristics like PS, ZP, EE%, cytotoxicity, release behavior and antimicrobial activity.

Arginine-conjugated chitosan nanoparticles for topical arginine release in wounds

Arginine is a conditionally essential amino acid in the healing process. Catabolized by nitric oxide synthases and arginases, arginine is rapidly depleted during the healing process of chronic wounds, hampering collagen synthesis, and other proteins that contribute to tissue regeneration. The administration of arginine at a wound site can compensate for its deficiency. To avoid its rapid metabolism, its sustained release in the wound bed is desired. In this work, arginine was encapsulated in arginine-modified chitosan nanoparticles (NP-CHITARG) to have arginine-conjugated chitosan polymer (CHITARG) as a late source of arginine after the sustained release of the drug encapsulated from the nanoparticle. The conjugate CHITARG was characterized by proton nuclear magnetic resonance, thermal and elemental analysis, and scanning electron microscopy. NP-CHITARG, obtained by a modified nanoprecipitation method, was characterized in terms of size, polydispersity, zeta potential, morphology, and encapsulation efficiency of arginine. In vitro cytotoxicity assay was also performed on fibroblast cells (NIH-3T3). NP-CHITARG dispersions showed 177 ± 35 nm, positive zeta potential, and pH 6. Encapsulation of arginine in NP-CHITARG increased 1.5-fold the size of the nanoparticles and decreased the pH of the dispersions to 5.5. NP-CHITARG was able to encapsulate about 10% of arginine. The release of arginine remained constant and slow after a burst release of approximately 20%. Nanoparticles were not cytotoxic to fibroblasts. The amount of arginine slowly released over time combined with CHITARG's antimicrobial and anticoagulant properties suggest a promising effect of nanoparticles in the treatment of wounds.

Carbamazepine and levetiracetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies

Objective: The aim of this study was to develop the PLGA nanoparticles (NPs) containing carbamazepine (CBZ) and levetiracetam (LEV) combination (CBZ + LEV) for the treatment of epilepsy and to in vitro characterize the prepared NPs.Significance: LEV and CBZ, which are antiepileptic drugs, are used in the treatment of epilepsy. Nano-sized formulations are prepared to use for different purposes such as to improve the solubility/the physicochemical properties and bioavailability of drugs, to decrease their doses and frequency of administration, and to reduce side effects of drugs.Methods: CBZ + LEV-PLGA-NPs were prepared by a modified nanoprecipitation method and in vitro and in vivo characterized. Also, the antiepileptic effect of the NPs was evaluated in vivo in a rat epilepsy model.Results: The mean particle size and zeta potential of CBZ + LEV-PLGA-NPs were 180.62 ± 6.260 nm and –27.08 ± 3.110 mV, respectively. The values of encapsulation efficiency (EE%) of CBZ and LEV were 51.00 ± 5.944% and 2.05 ± 0.367%, respectively. CBZ showed a biphasic release profile with initial burst release followed by a sustained release. Ninety percent of CBZ was released from NPs within two days; however, % LEV release from NPs reached about 80% within 30 min.Conclusion: Our results showed that a decrease in seizure scores in the group treated with CBZ + LEV was observed and also, CBZ + LEV and CBZ + LEV-PLGA-NPs had similar antiepileptic activity. The NPs containing CBZ + LEV might be beneficial in the treatment of epilepsy.

In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma.

The goal of this study is to develop optimized chitosan-coated Simvastatin (SIM) nanoparticles (NPs) loaded in an in situ gel (ISG) formulation via a face-centered central composite design (FCCCD). Coated SIM-NPs were doped with Quercetin (QRC) using a modified nanoprecipitation method. The concentrations of poloxamer 188 (A) and chitosan (B) at five different levels, plus/minus alpha (+1.414 and −1.414: axial points), plus/minus 1 (factorial points) and the center point were optimized for particle size (PS-Y1), entrapment efficacy (EE-Y2) and stability index (SI-Y3). Based on the desirability approach, a formulation containing poloxamer 188 0.24% and chitosan 0.43% renders the prerequisites of optimum formulation for preparing SIM–QRC NP-loaded ISG. Scanning microscopy showed spherical SIM-NPs, indicating monodispersity in the range of 0.50 ± 0.04 nm with a charge of +32.42 mV. The optimized formulation indicated the highest EE 79.67% and better stability at 4 °C. Drug release from SIM–QRC NP-loaded ISG was slower to plateau by up to 96 h and, at the end of 168 h, only 65.12% of SIM was released in a more controlled manner in comparison to SIM–QRC NPs and plain SIM. ISG formulation showed a considerable increase in apoptosis occurrence through caspase-3 mediation and it also enhanced the tumor suppressor protein levels. Enhanced biological activity of SIM was observed due to QRC enabling promising drug and polymer synergistic interaction. The proposed formulation can provide a breakthrough in localized therapy, overcoming the potential drawbacks of systemic chemotherapy for tongue carcinoma.

Nanostructural Control Enables Optimized Photoacoustic–Fluorescence–Magnetic Resonance Multimodal Imaging and Photothermal Therapy of Brain Tumor

AbstractThe performance of current multimodal imaging contrast agents is often constrained by the tunability of nanomaterial structural design. Herein, the influence of nanostructure on the overall imaging performance of a composite nanomaterial for multimodal imaging of brain tumors is studied. Newly designed near‐infrared molecules (TC1) are encapsulated into nanocomposites with ultrasmall iron oxide nanoparticles (UIONPs), forming stable nanoagents for multimodal imaging and photothermal therapy (PTT). Through a modified nanoprecipitation method, the synthesis of nanocomposites denoted as HALF is realized, in which UIONPs are restricted to half of the nanosphere. Such a unique nanostructure that physically separates TC1 and UIONPs is found with capabilities of mitigating fluorescence quenching, preserving the good performance of photoacoustic imaging, and enhancing the magnetic resonance imaging signals. Decorated with a peptide ligand cRGD for better brain tumor targeting, HALF‐cRGD is evaluated both in vitro and in vivo as imaging contrast agents and photothermal therapeutic agents. The good imaging performance and PTT effect of HALF‐cRGD in mice models indicate that the rational design and control of nanostructures could optimize multimodal imaging performance using the same components.

Shape mediated splenotropic delivery of buparvaquone loaded solid lipid nanoparticles.

Buparvaquone (BPQ)-loaded asymmetric solid lipid nanoparticles (SLN) prepared by a modified nanoprecipitation method were evaluated for splenotropic drug delivery. BPQ SLN exhibited an average particle size of 650.28 ± 6.75nm with polydispersity index ≤ 0.3, entrapment efficiency of 96.57 ± 0.190%, and drug loading of 24.63 ± 0.042%. Scanning electron microscopy (SEM) revealed elongated particles with flattened and rounded edges. Aspect ratio, an important determinant of asymmetricity of the BPQ SLN, measured as the ratio of average length (1143 ± 0.083nm) to width (419 ± 0.031nm) was found to be 2.727 ± 0.19. The hemolytic potential of 10.86 ± 0.04% and good serum stability suggested feasibility for intravenous administration. 99mTc-labeled BPQ SLN revealed high radiolabeling efficiency (> 95%) and good stability. Intravenous administration in mice revealed > 75% accumulation in the reticuloendothelial system organs. The percent radioactivity per gram of organ was in the order spleen > kidney > lungs > liver > lymph nodes, with high splenic accumulation and significantly lower concentration in the liver. An astoundingly high spleen/liver ratio with a maximum of 11.94 ± 1.37 at 3h, which confirmed high splenic uptake is attributed to Kupffer cell bypass. Other factors contributing to splenotropy are the rigidity and the low molecular weight of the lipid in the BPQ SLN which enabled translocation of the particles into the splenic pulp. Our study proposes asymmetric BPQ SLN as a promising splenotropic delivery system for improved efficacy in theileriosis, a spleen resident infection.

Docetaxel-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles in human breast cancer and human cervical cancer therapy

Taxane-based chemotherapy-loaded drug delivery systems have great potential for cancer treatment. The docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS) nanoparticles and the docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate) (PAM-PBLG) nanoparticles were designed using a modified nanoprecipitation method. The particle size, encapsulation efficiency (EE), and in vitro release characteristics of the nanoparticles were tested. The effects of the two nanoparticles on the cellular uptake and cell viability on human cervical cancer cell line Hela and the human breast cancer cell line MCF-7 were compared. Furthermore, their antitumor efficiency was evaluated through in vivo tumour growth experiment in comparison with free DTX. PAM-PBLG-b-TPGS nanoparticles displayed high EE, smaller diameter, and a nice releasing profile. Besides, based on the high EE and ‘self-controlled’ drug release of the DTX-loaded PAM-PBLG-b-TPGS nanoparticles, they exhibited stronger cytotoxicity (lower survival rate) and higher uptake rate than DTX-loaded PAM-PBLG nanoparticles in Hela cells and MCF-7 cells. Furthermore, compared with DTX-loaded PAM-PBLG nanoparticles and free DTX, DTX-loaded PAM-PBLG-b-TPGS nanoparticles produced a potent anti-tumour effect. Thus, the DTX-loaded PAM-PBLG-b-TPGS nanoparticles provide a novel attractive nanocarrier for the DTX delivery of chemotherapy to human breast cancer cells and human cervical cancer cells.

Development of Hydrophilic Drug Encapsulation and Controlled Release Using a Modified Nanoprecipitation Method

The improvement of the loading content of hydrophilic drugs by polymer nanoparticles (NPs) recently has received increased attention from the field of controlled release. We developed a novel, simply modified, drop-wise nanoprecipitation method which separated hydrophilic drugs and polymers into aqueous phase (continuous phase) and organic phase (dispersed phase), both individually and involving a mixing process. Using this method, we produced ciprofloxacin-loaded NPs by Poly (d,l-lactic acid)-Dextran (PLA-DEX) and Poly lactic acid-co-glycolic acid-Polyethylene glycol (PLGA-PEG) successfully, with a considerable drug-loading ability up to 27.2 wt% and an in vitro sustained release for up to six days. Drug content with NPs can be precisely tuned by changing the initial drug feed concentration of ciprofloxacin. These studies suggest that this modified nanoprecipitation method is a rapid, facile, and reproducible technique for making nano-scale drug delivery carriers with high drug-loading abilities

Nanoparticles based on a PEGylated methacrylate copolymer as vehicles for hydrophilic antimicrobial additives: a study on chemical interactions with a benzoic acid probe molecule

Release systems for bioactive compounds have been increasingly developed in various fields, such as pharmacy, agriculture, food and cosmetics. The most challenging stage in the implementation of these technologies is the selection of vehicles because they must efficiently encapsulate active principles without altering their activity and allow their controlled release. Herein, we report the synthesis of a poly(ethylene glycol)-block-poly(2-dimethylaminoethyl methacrylate-co-(butyl methacrylate-co-methyl methacrylate)) via atom transfer radical polymerisation at a molar ratio of methacrylic monomers of 2:1:1. The copolymer was evaluated as a precursor in the fabrication of nanostructured vehicles for benzoic acid used as a probe molecule. Infrared spectroscopy and hydrogen nuclear magnetic resonance spectroscopy showed that benzoic acid and the copolymer interacted through the formation of hydrogen bonds that involved amine groups on 2-dimethylaminoethyl methacrylate units and the carboxylic acid group. Polymer particles loaded with benzoic acid prepared via a modified nanoprecipitation method exhibited average diameters shorter than 200 nm. They were positively charged and colloidally stable in a pH range of 5.0 to 8.0. With these nanoparticles, benzoic acid achieved a controlled release.

Nose-to-brain delivery of lamotrigine-loaded PLGA nanoparticles.

Direct nose-to-brain delivery of drugs and faster onset of action have made intra-nasal route a much sought-after alternative to conventional routes of drug delivery to the brain. Lamotrigine is used for the treatment and management of neuropathic pain, and in the present work, lamotrigine (LTG)-PLGA nanoparticles were developed for intra-nasal delivery. The LTG-PLGA nanoparticles were prepared using modified nanoprecipitation method via high-speed homogenization and ultra-sonication techniques. Entrapment efficiency (EE%) of developed LTG-PLGA-NPs was found to be 84.87 ± 1.2% with drug loading of 10.21 ± 0.89%. The particle size of developed nanoparticles was found to be 184.6nm with PDI value of 0.082 and zeta potential of - 18.8mV. Dissolution profiles were studied in PBS (pH7.4), simulated nasal fluid, and simulated cerebrospinal fluid where almost complete release was observed within 5h in CSF. In vitro, cytotoxicity was analyzed using MTT assay where dose-dependent cytotoxicity was observed for developed LTG-PLGA-NPs. In vitro cytokine analysis showed positive effects of LTG-PLGA-NPs as pro-inflammatory cytokine suppressors. Further, in vivo studies were performed for radiolabeled formulation and drug (99mTc-LTG-PLGA-NPs and 99mTc-LTG-aqueous) using Sprague Dawley rats where with the help of gamma scintigraphy studies, various routes of administration viz. oral, intra-nasal, and intra-venous were compared. Various pharmacokinetic parameters were evaluated using biodistribution studies to estimate the drug levels in blood and brain. For 99mTc-LTG-PLGA-NPs via intra-nasal route, drug targeting efficiency (DTE%) was found to be 129.81% and drug target organ transport (DTP%) to be 22.81% in brain with Cmax of 3.82%/g within Tmax 1.5h. Thus, the developed PLGA nanoparticles for intra-nasal delivery provide a possible alternative for existing available drug formulation for neuropathic pain management.