Rapid Systemic Elimination Research Articles

Role of Polyphenols, Their Nano-formulations, and Biomaterials in Diabetic Wound Healing.

A diabetic wound is one of the major complications arising from hyperglycemia, neuropathy, and oxidative stress in diabetic patients. Finding effective treatments for diabetic wounds has been difficult owing to the complex pathophysiology of diabetic wound environments. Chronic wounds are notoriously difficult to treat with conventional wound care methods. In recent years, polyphenols found in plants have received much interest as a potential treatment for diabetic wounds. Their key benefits are their safety and the fact that they act through many molecular routes to treat diabetic wounds. However, problems with their formulation development, including lipophilicity, light sensitivity, limited membrane permeability, rapid systemic elimination, and enzymatic degradation, prevented them from gaining clinical attention. This article highlights and discusses the mechanism of polyphenols and various polyphenol-based drug delivery systems used till now to treat diabetic wounds. The consideration that should be taken in polyphenols-based nano-formulations and their prospect for diabetic wounds are also discussed briefly.

Transforming Cancer Treatment with Nanotechnology: The Role of Berberine as a Star Natural Compound.

Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. This review introduced the expansive spectrum of BBR's anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery. Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. Nano-delivery systems increase drug concentration at the tumor site by improving pharmacological activity and tissue distribution, enhancing drug bioavailability. Organic nanocarriers have advantages for berberine delivery including biocompatibility, encapsulation, and controlled release of the drug. While the advantages of inorganic nanocarriers for berberine delivery mainly lie in their efficient loading ability of the drug and their slow release ability of the drug. This review introduced the expansive spectrum of BBR's anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery.

Solid Lipid Nanoparticles Encapsulating Naturally Derived Boschniakine Mitigates Induced Diabetic Nephropathy

Boschniakine, a bioalkaloid isolated from the Tecoma stans plant, has been reported to be traditionally utilized for the management of diabetes in model systems through multiple biochemical mechanisms. Studies on Boschniakine are sparse, also, taking into consideration that poor absorption, a rapid metabolic rate, and rapid systemic elimination could limit bioalkaloids’ pharmacological efficacy. To recognize such limitations, we propose the use of highly bioavailable Boschniakine-Solid Lipid Nanoparticles (Bos-SLNPs). This study examined the potential molecular mechanisms underlying the anti-diabetic effects of Bos-SLNP. Bos-SLNP (25 and 50 mg/kg) was evaluated for 30 days for its antidiabetic activity in streptozotocin-induced Type 1 and Type 2 diabetic rats. In addition, the RT-PCR technique was used to determine messenger-RNA expression of Interleukin-1, Interleukin-6, and Tumor Necrosis Factor-alpha in renal tissue. haematoxylin and eosin staining and Western blotting were used to find differences in the nuclear factor erythroid 2-related factor 2/heme oxygenase/Nuclear Factor-κB signaling pathway and how its proteins were expressed. Bos-SLNPs treatment resulted in an increase in the expression of nuclear factors erythroid 2-related factor 2 and heme oxygenase-1 and a decrease in the expression of Nuclear factor-B. This was because Bos-SLNPs have a protective mechanism, which comes from their anti-inflammatory and anti-oxidant properties. Bos-SLNPs exhibited a protective effect against diabetic nephropathy in rats induced with streptozocin, possibly via the nuclear factor erythroid 2-related factor pathway 2 / heme oxygenase 1/ nuclear factor B.

Biodegradable Polymeric Nanoparticles Loaded with Flavonoids: A Promising Therapy for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic non-specific inflammation in the gastrointestinal (GI) tract, primarily affecting the ileum and colon. The incidence of IBD has risen sharply in recent years. Despite continuous research efforts over the past decades, the aetiology of IBD is still not fully understood and only a limited number of drugs are available for its treatment. Flavonoids, a ubiquitous class of natural chemicals found in plants, have been widely used in the prevention and treatment of IBD. However, their therapeutic efficacy is unsatisfactory due to poor solubility, instability, rapid metabolism, and rapid systemic elimination. With the development of nanomedicine, nanocarriers can efficiently encapsulate various flavonoids and subsequently form nanoparticles (NPs), which greatly improves the stability and bioavailability of flavonoids. Recently, progress has also been made in the methodology of biodegradable polymers that can be used to fabricate NPs. As a result, NPs can significantly enhance the preventive or therapeutic effects of flavonoids on IBD. In this review, we aim to evaluate the therapeutic effect of flavonoid NPs on IBD. Furthermore, we discuss possible challenges and future perspectives.

ELU-FRα-1: A study to evaluate ELU001 in patients with solid tumors that overexpress folate receptor alpha (FRα).

TPS3158 Background: ELU001 is a novel, first-in-class, new molecular entity described as a C’Dot Drug Conjugate (CDC). ELU001 consists of ̃12 folic acid targeting moieties and ̃22 exatecan topoisomerase-1 inhibitor payloads on Cathepsin-B cleavable linkers covalently bound to the surface of each silicon core/polyethylene glycol C’Dot nanoparticle. CDCs are small in size (̃6 nm), have a greater ability to penetrate into and through tumors as compared to ADCs, and are rapidly eliminated by the kidneys. The rapid systemic elimination is expected to lead to less toxicity than is observed with targeting platforms like ADCs that have a longer half-life in circulation. ELU001’s high avidity is believed to promote internalization into FRα overexpressing cancer cells, selectively delivering it’s ̃22 molecules of payload. The first-in-human clinical trial, ELU-FRα-1, is currently recruiting patients that have advanced, recurrent or refractory FRα overexpressing tumors considered to be topoisomerase 1 inhibitor-sensitive based on the literature, and, in the opinion of the Investigator, have no satisfactory therapeutic options available. Methods: This is a Phase 1 / 2 multicenter, open label clinical trial with two parts: Part 1 Dose Escalation and Part 2 Tumor Group Expansion Cohort(s). In Part 1, patients with cancer types with a high likelihood of having FRα overexpressing tumors based on historical data, (specifically, ovarian, endometrial, colorectal, gastric, gastroesophageal junction, triple negative breast, or non-small cell lung cancers, or cholangiocarcinoma), will be enrolled to the study. Patients will receive ELU001 on a weekly dose regimen (QW) (once a week for 3 weeks, 1 week rest) or every other week dose regimen (Q2W, with no rest between cycles). Retrospective analysis of FRα expression will be determined. Part 2 uses a Simon’s Two-Stage design to evaluate 4-6 tumor group expansion cohorts, each consisting of patients with specific tumor types (to be identified based on emerging data) that overexpress FRα (prospectively determined prior to enrollment). The primary objective for Part 1 is to identify the MTD/RP2D and for Part 2 is ORR. Dose Escalation will recruit about 25 patients per dose regimen (QW or Q2W). Dose Expansion will recruit about 15 patients per tumor group expansion cohort. Secondary objectives are anti-tumor activity (DOR, PFS, TFST, PFS2, OS), frequency, severity and tolerability of adverse events, PK, ADA, and FRα expression assessments. The study is actively enrolling in the US – Cohorts 1-2 have been completed without DLT. Enrollment to Cohort 3 began in December 2021. Clinical trial information: NCT05001282 .

Superior Pharmacokinetic Profile of an Innovative, Next Generation Curcumin Formula

IntroductionCurcumin is the major bioactive component of turmeric or Curcuma longa L., a widely used spice, food colorant, preservative as well as medicinal agent in Indian and Chinese remedies. Numerous studies have demonstrated its potential benefits for heart health, immunity, diabetes, arthritis as well as joint health and mobility. Currently, curcumin‐based products in capsules, ointments, tablets, and cosmetics are marketed worldwide. One important drawback of using curcumin is its poor bioavailability and hence the need to use it at high doses to achieve measurable plasma levels and efficacy – this limits both consumer compliance and product formulation. Curcumin’s poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination contributes to its poor bioavailability. To help overcome this major limitation of curcumin, we developed a proprietary curcumin formulation (Curcuwin Ultra+) (CU+) to enhance its bioavailability. We hypothesized that the formulation would protect the curcuminoids from degradation at intestinal alkaline pH conditions, and through this mechanism, significantly increase the availability of curcuminoids in blood and at the tissue level.GoalOur goal was to measure the pharmacokinetic profile of CU+ vs. a standard turmeric extract (STE).MethodA randomized, double‐blind, crossover study design involving 24 healthy volunteers under fasting conditions was implemented. Subjects received a single dose of 250 mg CU+, 500 mg CU+ and 1900 mg of STE. Blood samples before dosing, and at various time points post dosing up to 24 hours were collected. Total curcuminoids were measured using a validated LC‐MS/MS method. Formulations were compared based on Cmax, AUC0‐6, AUC0‐24, Tmax, t1/2, and relative absorption.ResultsMaximum serum concentration (Cmax) and total systemic exposure (AUC0‐6 and AUC0‐24) for total curcuminoids were significantly higher (p<0.05) for both doses of CU+ vs. STE. For example, AUC0‐6 was 144 and 149 times greater for CU+ at 250 mg and 500 mg respectively compared to 1900 mg of STE. Additionally, CU+ showed 40% faster absorption as measured by Tmax vs. the STE (p<0.05). No adverse events were observed.ConclusionsThese pharmacokinetic data demonstrates the ability of this curcumin formulation to deliver superior bioavailability vs. STE, and, at doses that are considerably lower than STE and several other commercially available curcumin products. This has important relevance to consumer compliance in terms of lowering curcumin dose and frequency of dosing. Since maximizing bioavailability influences the therapeutic effects of a compound, the next phase of our research program is to determine if this enhanced bioavailability can be translated to an efficacious benefit of CU+.

PH-responsive and CD44-targeting polymer micelles based on CD44p-conjugated amphiphilic block copolymer PEG-b-HES-b-PLA for delivery of emodin to breast cancer cells

Herein, an amphiphilic block copolymer CD44-targeting peptide-conjugated polyethylene glycol-block-hydroxyethyl starch-block-poly (L-lactic acid) (CD44p-conjugated PEG-b-HES-b-PLA) are synthesized, which could self-assemble into the pH-responsive and CD44-targeting polymer micelles against breast cancer cells MDA-MB-231. Emodin (Emo) is a natural anthraquino with pharmacological activities in anti-tumor effects. However, Emo suffers from poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, resulting in unsatisfactory treatment outcomes. Nanotechnology-based drug delivery systems have proven great potential for cancer chemotherapy. The constructed polymeric micelles Emo@CD44p-PM have exhibited an average size of 154.5 ± 0.9 nm characterized by DLS and TEM. Further, the Emo@CD44p-PM have effective Emo-loading capacity, good thermal stability, and pH responsiveness. Intracellular uptake study shows the enhanced cellular internalization of Emo@CD44p-PM due to the increased exposure of CD44p enhances the cellular internalization of Emo@CD44p-PM effectively. Furthermore, the in vitro results showed Emo@CD44p-PM has been observed good biocompatibility and anti-tumor effects. Therefore, the polymeric micelles Emo@CD44p-PM provide a promising delivery strategy of targeted therapy for breast cancer.

Curcuminoid (CRE-Ter)/Liposome as delivery platform for anti-osteoclastogenesis via NF-κB/ERK pathways in RANKL-induced RAW 264.7 cells through PLA foams

AimsCurcuminoid (CRE-Ter) is the active component of turmeric, and is widely understood to offer anticancer, antioxidant, and anti-inflammatory properties. The drawbacks, however, include rapid metabolism and systemic elimination as well as minimal bioavailability. In an attempt to address the issue of bioavailability, this study seeks to encapsulate CRE-Ter in a liposome before its incorporation on PLA foams in order to inhibit the process of osteoclastogenesis which takes place in RANKL-induced RAW 264.7 cells. Main methodsHaving encapsulated the CRE-Ter into the liposomes, the influence of the release of liposomal CRE-Ter from PLA foams in order to inhibit the process of osteoclastogenesis in the case of RANKL-induced RAW 264.7 cells was investigated. By measuring the decline in tartrate-resistant acid phosphatase (TRAP) content it was possible to evaluate the influence of CRE-Ter/Liposome upon osteoclastogenesis in vitro. Immunocytochemistry was employed to assess the marker for the monocyte/macrophage cells F4/80 content, while Western blots were used to evaluate the underlying mechanisms involved. Key findingsThe findings demonstrate a novel method which employs tissue engineering scaffolds, which are produced to work alongside advanced additive manufacturing techniques with their basis in concepts from the field of alternative medicine. Initially, it was confirmed that CRE-Ter/Liposome at 20 μg/ml is able to inhibit the creation of multinucleated osteoclasts which are induced by the receptor activator of the nuclear factor-κB ligand (RANKL) in RAW 264.7 cells. It was shown that the CRE-Ter/liposome was able to increase the F4/80 content (F4/80 immunohistochemistry) in the RANKL treated RAW 264.7 cells. The TRAP content was lowered by the CRE-Ter/liposome along with the osteoclast-specific gene content such as cathepsin K, via the use of liposome-encapsulated PLA foams. When treated with CRE-Ter/liposome, RANKL-induced NF-κB and ERK components such as NF-κB-p65, ERK, phospho-NF-κB-p65, and phospho-ERK pathways were all suppressed. SignificanceThe successful encapsulation of CRE-Ter into the liposomes offered a new opportunity to provide a new inhibitor of osteoclastogenesis and offers the possibility of developing treatments capable of addressing diseases which concern abnormal bone lysis.

Bioavailability of berberine: challenges and solutions

Berberine is a quaternary benzylisoquinoline alkaloid with multiple pharmacological effects used for the treatment of hypertension, tumors, bacterial infections, inflammation, HIV, and cardiac diseases. In phase I clinical trials, berberine is safe at excessive doses but manifests poor bioavailability. Major challenges like poor absorption, rapid metabolism, and rapid systemic elimination are responsible for low plasma and tissue levels of berberine. Various strategies have been undertaken by several researchers to overcome this issue and enhance the bioavailability of berberine. This includes the design of new formulation strategies; novel drug delivery systems (NDDS) like liposomes, nanosized dosage forms, phospholipid complexes, mucoadhesive microparticles, and micoemulsions; the use of adjuvants; and the design of structural analogous of berberine. This review focuses on the occurrence of berberine in numerous plants and its pharmacological activities as evidenced through numerous preclinical and clinical studies. The later part of this review highlights the bioavailability issue of berberine which arises due to its poor absorption, elevated rate and extent of metabolism, and quick elimination and clearance from the body. A systematic effort has beenmade to analyze the various formulation strategies, including the design of newer berberine analogues and derivatives. These strategies can be further explored to increase the bioavailability, medicinal value, and application of this promising molecule.

Quantification of BNN27, a novel neuroprotective 17-spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration.

BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57BL/6 mice and 48 Sprague–Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro‐orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography‐mass spectrometry (LC‐MS). Non‐compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant k el = 0.465 h−1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (C max) in the retina was detected at 2 h (tCmax) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC‐MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood–retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.

Pharmacokinetics of gemcitabine and its amino acid ester prodrug following intravenous and oral administrations in mice

Gemcitabine is an intravenously administered anti-cancer nucleoside analogue. Systemic exposure following oral administration of gemcitabine is limited by extensive first-pass metabolism via cytidine deaminase (CDA) and potentially by saturation of nucleoside transporter-mediated intestinal uptake. An amino acid ester prodrug of gemcitabine, 5′-l-valyl-gemcitabine (V-Gem), was previously shown to be a substrate of the intestinally expressed peptide transporter 1 (PEPT1) and stable against CDA-mediated metabolism. However, preliminary studies did not evaluate the in vivo oral performance of V-Gem as compared to parent drug. In the present study, we evaluated the pharmacokinetics and in vivo oral absorption of gemcitabine and V-Gem following intravenous and oral administrations in mice. These studies revealed that V-Gem undergoes rapid systemic elimination (half-life < 1 min) and has a low oral bioavailability (<1%). Most importantly, the systemic exposure of gemcitabine was not different following oral administration of equimolar doses of gemcitabine (gemcitabine bioavailability of 18.3%) and V-Gem (gemcitabine bioavailability of 16.7%). Single-pass intestinal perfusions with portal blood sampling in mice revealed that V-Gem undergoes extensive activation in intestinal epithelial cells and that gemcitabine undergoes first-pass metabolism in intestinal epithelial cells. Thus, formulation of gemcitabine as the prodrug V-Gem does not increase systemic gemcitabine exposure following oral dosing, due, in part, to the instability of V-Gem in intestinal epithelial cells.

Bioanalytical method by HPLC-FLD for curcumin analysis in supplemented athletes

In sports, curcumin, a substance derived from the rhizome of Curcuma longa (turmeric) plant with antioxidant effect 8 times greater than vitamin E, has attracted the attention of scientists because of its potent antioxidant action, since in athletes subjected to intense exercise the—endogenous mechanisms of neutralization of reactive species are saturated. However, the pharmacokinetic characteristics of curcumin do not favor its medicinal use due to its low absorption, accelerated metabolism and rapid systemic elimination. Thus, the determination of plasma levels in supplemented patients is a crucial step in their pharmacodynamic evaluation. Therefore, the objective of this work was to develop and validate an analytical method by HPLC-FLD for curcumin evaluation in plasma of supplemented athletes. Luna column (C18; 150 × 4 mm; 3 µm), acetonitrile: acetic acid pH 3.2 (45:55 to 60:40) as mobile phase, flow rate of 1 mL min−1, excitation at 429/285 nm and emission at 529 nm and injection of 10 µL were the chromatographic conditions used. Plasma samples were extracted using ethylacetate and methanol (95: 5, 500 µL) and estradiol (30 µg mL−1) as internal standard, with subsequent stirring (3 min) and centrifugation (8 min) (triple extraction). The organic fraction was evaporated under N2 (20 min) and the dried residue reconstituted in acetonitrile. The method was linear between 44 and 261 ng mL−1, showing intra-day (2.05.6%) and inter-day (4.0–5.1%) precision with accuracy and selectiveness (curcumin tR = 8.7 min and internal standard tR = 13.9 min with relative recovery of 83.2%). So, it can be successfully used for curcumin evaluation in plasma samples from supplemented athletes, as well as being an alternative and advantageous method to UV–Vis and MS/MS in bioavailability studies.

A review of ultrasound-mediated microbubbles technology for cancer therapy: a vehicle for chemotherapeutic drug delivery

AbstractBackground:The unique behaviour of microbubbles under ultrasound acoustic pressure makes them useful agents for drug and gene delivery. Several studies have demonstrated the potential application of microbubbles as a non-invasive, safe and effective technique for targeted delivery of drugs and genes. The drugs can be incorporated into the microbubbles in several different approaches and then carried to the site of interest where it can be released by destruction of the microbubbles using ultrasound to achieve the required therapeutic effect.Methods:The objective of this article is to report on a review of the recent advances of ultrasound-mediated microbubbles as a vehicle for delivering drugs and genes and its potential application for the treatment of cancer.Conclusion:Ultrasound-mediated microbubble technology has the potential to significantly improve chemotherapy drug delivery to treatment sites with minimal side effects. Moreover, the technology can induce temporary and reversible changes in the permeability of cells and vessels, thereby allowing for drug delivery in a spatially localised region which can improve the efficiency of drugs with poor bioavailability due to their poor absorption, rapid metabolism and rapid systemic elimination.

Liposome-Encapsulated Curcumin-Loaded 3D Printed Scaffold for Bone Tissue Engineering.

Curcumin, the active constituent for turmeric, is known for its antioxidant, anti-inflammatory, anticancer, and osteogenic activities. However, it shows extremely poor bioavailability, rapid metabolism, and rapid systemic elimination. In this study, we have increased the bioavailability of curcumin by encapsulating it in a liposome, followed by the incorporation onto 3D printed (3DP) calcium phosphate (CaP) scaffolds with designed porosity. 3DP scaffolds with a designed shape and interconnected porosity allow for the fabrication of patient-specific implants, providing new tissue ingrowth by mechanical interlocking between the surrounding host tissue and the scaffold. Upon successful encapsulation of curcumin into the liposomes, we have investigated the effect of liposomal curcumin released from the 3DP scaffolds on both human fetal osteoblast cells (hFOB) and human osteosarcoma (MG-63) cells. Interestingly, liposomal curcumin released from the 3DP scaffold showed significant cytotoxicity toward in vitro osteosarcoma (bone cancer) cells, whereas it promoted osteoblast (healthy bone cell) cell viability and proliferation. These results reveal a novel approach toward the fabrication of tissue engineering scaffolds, which couples the advanced additive manufacturing technology with the wisdom of alternative medicine. These bifunctional scaffolds eradicate the osteosarcoma cells and also promote osteoblast proliferation, offering new opportunities to treat bone defects after tumor resection.

Liposomes encapsulated dimethyl curcumin regulates dipeptidyl peptidase I activity, gelatinase release and cell cycle of spleen lymphocytes in-vivo to attenuate collagen induced arthritis in rats

Rheumatoid arthritis (RA) is an autoimmune disease and characterized by the excessive cell proliferation, abnormal cell cycle of lymphocytes and synovial cells. The therapeutic effects of curcumin in active RA patients were reported, but limited by its insolubility and rapid systemic elimination. Dimethyl curcumin (DiMC) is a metabolically stable analogue of curcum with anti-inflammatory property. In this study, liposomes encapsulated dimethyl curcumin (Lipo-DiMC) was prepared to improve the bioavailability and metabolic-stability; collagen induced arthritis (CIA) rat model was employed to investigate the effects of Lipo-DiMC treatments during CIA progress. Physical assessments and routine-blood-test were performed. Fresh spleen lymphocytes were isolated from normal, CIA and Lipo-DiMC-treated CIA rats; flow-cytometry for cell-cycle analysis, western-blotting for intracellular signal pathway protein expressions, gelatin-zymography for matrix-metalloproteases 2/9 (MMP-2/9) and GF-AFC for dipeptidyl-peptidase I (DPPI) activity assay.Compared with untreated CIA rats, Lipo-DiMC treatments relieved paw-swellings, suppressed the increments of immunocytes numbers and inhibited DPPI and MMP-2/9 over-activity in blood. Lipo-DiMC adjusted CIA-induced cell cycle dysfunction at G0/G1-phase and S-phase of spleen lymphocytes for CIA rats. The intracellular expression-trends of P38, P21, Bcl-2, JNK-1 and DPPI of spleen lymphocytes were observed during CIA progress with and without Lipo-DiMC administrations. Lipo-DiMC exhibited its therapeutic functions by attenuating CIA development in rats, associated with down-regulating CIA-induced lymphocytes numbers, inhibiting over-expressed of DPPI and MMP-2/9, and adjusting cell cycles. These findings provide a new insight into the mechanism of Lipo-DiMC treatment in CIA rat model and suggest that Lipo-DiMC could be considered as a potential drug for RA treatment.

Design of epigallocatechin gallate loaded PLGA/PF127 nanoparticles and their effect upon an oxidative stress model

The epigallocatechin gallate (EGCG) is the most abundant and powerful antioxidant found in green tea. This polyphenol has been proven to have great therapeutic potential in different diseases such as cancer, diabetes, and neurodegenerative diseases. However, the limitations imposed by their low stability and rapid systemic elimination lessen their bioavailability and therapeutic efficacy. To overcome the above problems, EGCG was incorporated into poly(lactic-co-glycolic acid) and Pluronic® F127 based nanoparticles (PLGA/PF127). Nanoparticles were prepared using the emulsion/solvent evaporation method resulting in particles with a mean size around 100 nm, low polydispersity index ≤0.1, high drug encapsulation efficiency (∼86%) and in vitro sustained release. The antioxidant efficacy of the EGCG nanoparticulate formulation was evaluated upon an in vitro oxidative stress model. Remarkably, we found for the first time that EGCG encapsulated in PLGA/PF127 nanoparticles prevent the rotenone-induced ROS generation, loss of mitochondrial membrane potential and DNA fragmentation in nerve-like cells. Therefore, our findings suggest the use of these nanoparticles system might be a great opportunity to test EGCG delivery as a potential therapeutic strategy in in vivo models of neurodegenerative diseases.

A Review on the preparation methods of Curcumin Nanoparticles

Design and development of herbal nanoparticles has become a frontier research in the nanoformulation arena. Curcumin is the main bioactive component contained in Curcuma longa, largely employed in traditional medicine. Recently, beneficial properties, useful for prevention and treatment of several disorders, have been discovered for this compound. Although curcumin has shown therapeutic efficacy against many human ailments, one of the major problems with curcumin is its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid systemic elimination. Therefore introduction of nanotechnology provides a solution towards increased bioavailability of curcumin. In this review, the various methods of preparation of curcumin nanoparticles are briefly discussed.

Liposomal curcumin and its application in cancer.

Curcumin (CUR) is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy.

Polymeric nanoparticles of (-)-epigallocatechin gallate: A new formulation for the treatment of ocular diseases

The epigallocatechin gallate (EGCG) is the most abundant and powerful antioxidant found in green tea. This polyphenol has been proven to have great therapeutic potential in different diseases such as cancer, diabetes, and neurodegenerative diseases. However, the limitations imposed by their low stability and rapid systemic elimination lessen their bioavailability and therapeutic efficacy. To overcome the above problems, EGCG was incorporated into poly(lactic-co-glycolic acid) and Pluronic® F127 based nanoparticles (PLGA/PF127). Nanoparticles were prepared using the emulsion/solvent evaporation method resulting in particles with a mean size around 100 nm, low polydispersity index ≤0.1, high drug encapsulation efficiency (∼86%) and in vitro sustained release. The antioxidant efficacy of the EGCG nanoparticulate formulation was evaluated upon an in vitro oxidative stress model. Remarkably, we found for the first time that EGCG encapsulated in PLGA/PF127 nanoparticles prevent the rotenone-induced ROS generation, loss of mitochondrial membrane potential and DNA fragmentation in nerve-like cells. Therefore, our findings suggest the use of these nanoparticles system might be a great opportunity to test EGCG delivery as a potential therapeutic strategy in in vivo models of neurodegenerative diseases.

Preparation, characterization and anti-inflammatory effects of curcumin loaded carboxymethyl cellulose acetate butyrate nanoparticles on adjuvant induced arthritis in rats

Rheumatoid Arthritis is a destructive illness and results in damage of joints and cartilages, followed by loss of function. Curcumin proved to be more effective in alleviating the symptoms of rheumatoid arthritis like tenderness and swelling of joints compared to regular drugs. However, its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and rapid systemic elimination. In our study, curcumin was molecularly dispersed in amorphous polymer and nanoparticles were produced by a rapid precipitation technique. Dynamic light scattering showed the particle size was 166.5 ± 4.2 nm. Differential Scanning Calorimetry (DSC) results showed that the drug in the nanoparticles was in the amorphous state. Drug loading efficiency in the nanoparticles was 73.41 ± 2.4%. The drug from the nanoparticle showed higher release compared to the pure as-received drug. Behavioral studies were conducted such as thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia, hematological assessment, radiographic analysis and various disease development parameters such as mobility score, joint stiffness, paw volume and locomotor activity was assessed after induction of arthritis using complete Freund's adjuvant in rats. Studies revealed that nanoparticles act as better anti-inflammatory agents and could give faster relief from pain.