Bioavailability Problems Research Articles

Formulation, Characterization and in vitro Release of Topical Nanoemulsion Containing Prednisolone-Derived Corticosteroid

Backround Prednisolone-Derived Corticosteroid (PDC), has anti-inflammatory activity in ocular administration. However, drug administration to the eye is extremely difficult due to the complex structure of the eye. Because of the ability of the eye to retain the drug and its physiology, the bioavailability of drugs applied to the eye is very low. Objective One of the methods to overcome bioavailability problem is to formulate the drug as a nanoemulsion (NE). NEs are thermodynamically stable, colloidal drug delivery systems. They have small globule size and high surface area. These properties give them the ability to cross the biological membrane and increase the therapeutic efficacy of the drug molecule. Methodology The high energy method was used to create a NE eye drop formulation containing PDC, and the effects of changing homogenization processes on NE formation were investigated. After deciding on the optimum formulation; characterization, assay and in vitro release studies were performed, and the stability of the formulation was followed for 12 months. Results The optimum formulation selected initially had 126.6 ± 40.12nm and 99.9 ± 1.2% PDC, it had 125.4 ± 41.20nm and 99.29 ± 1.3% PDC after 12months in 25 °C 40%RH conditions. Cytotoxicity studies have shown no significant cytotoxic effects in NE containing PDC. Conclusion The preparation and optimization of topical nanoemulsion formulations containing PDC for ocular inflammation treatment were achieved. The developed formulation was stable for 12months and no toxic effect was found in cell culture studies. This formulation could be useful as an alternative to PDC for ocular applications.

Advanced Targeted Therapy for Colorectal Cancer with Lipid Nanoparticles.

Targeted therapy for colorectal cancer (CRC) appears to have great potential with lipid nanoparticles (LNPs). The advances in LNP-based techniques, such as liposomes, exosomes, micelles, solid lipid nanoparticles (SLNs), nano-cubosomes, and plant- derived LNPs (PDLNPs), are explored in detail in this thorough review. Every platform provides distinct advantages: liposomes enable precise drug release and improved delivery; exosomes function as organic nanocarriers for focused treatment; SLNs offer greater stability; micelles enhance drug solubility and resistance; nano-cubosomes tackle low bioavailability; and PDLNPs offer biocompatible substitutes. The mechanisms, benefits, drawbacks, and therapeutic potential of these LNP platforms in the treatment of colorectal cancer are highlighted in the review. The review highlights how crucial it is to use these technologies for efficient CRC management and looks at potential future developments for them. The controlled release properties of liposomes and solid liposome nanoparticles (SLNs) improve the stability and bioavailability of medicinal compounds. On the other hand, exosomes and micelles provide answers for medication resistance and solubility issues, respectively. Novel strategies for resolving bioavailability problems and enhancing biocompatibility include nano-cubosomes and PDLNPs. These LNP-based systems are promising in clinical applications for boosting therapeutic efficacy, decreasing systemic toxicity, and facilitating tailored drug delivery. By incorporating these nanotechnologies into CRC treatment plans, present therapeutic approaches may be completely changed, and more individualized and efficient treatment choices may be provided. To completely comprehend the advantages and drawbacks of these LNP systems in therapeutic settings, as well as to and optimize them, more study is recommended by the review. Treatment for colorectal cancer may be much improved in the future thanks to developments in LNP-based drug delivery systems. These technologies hold great promise for improving patient outcomes and advancing the field of oncology by tackling important issues related to medication delivery and bioavailability.

Curcumin mediates glutathione depletion via metal–organic framework nanocarriers to enhance cisplatin chemosensitivity on esophageal cancer

Cisplatin (CDDP) is the primary drug used in the initial treatment of esophageal cancer (EC). However, its side effects and resistance can limit its effectiveness in clinical therapy. Curcumin (Cur)-mediated glutathione (GSH) depletion can reverse resistance, enhance the chemosensitivity of CDDP, and further improve the efficacy of platinum-containing chemotherapy in the treatment of esophageal cancer. However, it is also faced with problems of poor water solubility and low bioavailability in vivo, which severely hinders cancer treatments. In order to address these issues, we developed a novel nanotherapeutic system called CDCZA, combining Cur/CDDP/Cu/ZIF8@Au to enhance chemotherapy through GSH depletion and chemodynamic therapy through self-produced H2O2. Cu and CDDP were precisely co-loaded into Cu/ZIF8 nanoparticles using a one-pot method, then ultra-small gold nanoparticles mimicking glucose oxidase (Au nanoparticles) were embedded in the outer shell to create the CDCZA nano system. The released Cur could notably decrease intracellular GSH content and thus improve the chemosensitivity of CDDP, resulting in severe cellular apoptosis. And the Au nanoparticles effectively enabled chemodynamic therapy enhancement by accelerating the depletion of β-D-glucose into H2O2. As a result, the CDCZA nanoparticles showed increased tumor accumulation and improved antitumor effectiveness in a model of EC. Taken together, this work provides a new idea for the clinical design of efficient treatment reagents for EC.

An Updated Review Summarizing the Anticancer Potential of Poly(Lactic-co-Glycolic Acid) (PLGA) Based Curcumin, Epigallocatechin Gallate, and Resveratrol Nanocarriers.

The utilization of nanoformulations derived from natural products for the treatment of many human diseases, including cancer, is a rapidly developing field. Conventional therapies used for cancer treatment have limited efficacy and a greater number of adverse effects. Hence, it is imperative to develop innovative anticancer drugs with superior effectiveness. Among the diverse array of natural anticancer compounds, resveratrol, curcumin, and epigallocatechin gallate (EGCG) have gained considerable attention in recent years. Despite their strong anticancer properties, medicinally significant phytochemicals such as resveratrol, curcumin, and EGCG have certain disadvantages, such as limited solubility in water, stability, and bioavailability problems. Encapsulating these phytochemicals in poly(lactic-co-glycolic acid) (PLGA), a polymer that is nontoxic, biodegradable, and biocompatible, is an effective method for delivering medication to the tumor location. In addition, PLGA nanoparticles can be modified with targeting molecules to specifically target cancer cells, thereby improving the effectiveness of phytochemicals in fighting tumors. Combining plant-based medicine (phytotherapy) with nanotechnology in a clinical environment has the potential to enhance the effectiveness of drugs and improve the overall health outcomes of patients. Therefore, it is crucial to have a comprehensive understanding of the different aspects and recent advancements in using PLGA-based nanocarriers for delivering anticancer phytochemicals. This review addresses the most recent advancements in PLGA-based delivery systems for resveratrol, EGCG, and curcumin, emphasizing the possibility of resolving issues related to the therapeutic efficacy and bioavailability of these compounds.

7483 The Pharmacokinetic Profile of Lanreotide Autogel® Improved Long-Term Arrhythmia Fluctuations in Acromegalic Cardiomyopathy

Abstract Disclosure: M. Iwabuchi: None. Background: The prognosis of acromegaly is related to the status of cardiac complications. Ventricular premature contractions (VPC) are frequently observed in acromegaly, and it is very important to suppress fatal arrhythmias to improve long-term prognosis. Somatostatin analogs are widely used as pharmacotherapy for acromegaly, and they have been reported to improve cardiac prognosis. In comparison to LAR, lanreotide Autogel® has a unique property of self-aggregation under favorable conditions, leading to a stable structure of highly organized nanotubules and has a long half-life after subcutaneous injection determined by pseudo-first order kinetics. CASE: 55-year-old man visited a cardiologist for the treatment of PVCs and heart failure. Because of his acromegalic features, endocrinological and image examinations were performed, and diagnosis of acromegaly was confirmed. His GH was 7.17 ng/mL, IGF-1 566 ng/mL (Normal range: 59-215). Concerning excess of GH may cause nonischemic cardiomyopathy, administration of 20 mg of LAR once a month was started. GH and IGF-1 improved to1.52 ng/mL and 217 ng/mL respectively. The dose of LAR was increased to 30mg because of a remaining fluctuation of VPCs. Considering a possibility of the problem of bioavailability due to method of injection and the pharmacokinetics of LAR, administration of lanreotide Autogel® was started instead of LAR, with the result that an improvement of the fluctuation of the symptom was observed without remarkable change in GH and IGF-1. Arrhythmia status was assessed over time using Holter electrocardiography. Pretreatment Holter electrocardiogram showed 18% of total heart rates in PVCs. After LAR injection, the frequency of PVCs decreased to 3%, and 6 years after changing LAR to lanreotide, the frequency of PVCs decreased to 2%. Clinical Lessons: Simulated steady state pharmacokinetic profiles of LAR and lanreotide Autogel® differ significantly. During LAR treatment, serum concentrations of the drug are approximately stable, whereas the characteristic first-order kinetics of lanreotide Autogel® is superimposed on levels just before the next administration. The pharmacokinetic differences indicate that LAR can be better tailored to therapeutic levels, whereas serum levels of lanreotide must be high for part of the interval between injections to be effective in the period before the next administration. Lanreotide Autogel® has similar clinical effects compared to LAR for the treatment of cardiomyopathy of acromegaly and has the advantage of being available in a convenient pre-filled syringe and no necessity of injection by healthcare professionals. It is suggested that the pharmacokinetic profile of Lanreotide Autogel® resulted in decreased arrhythmia fluctuation in acromegalic hearts, which has been maintained for the past 6 years. Presentation: 6/3/2024

Enhancing Acute Migraine Treatment: Exploring Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for the Nose-to-Brain Route.

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented.

Fast Dissolving Film of Levocetirizine: Solubility Enhancement by forming Inclusion Complex with β-cyclodextrin, Formulation and Evaluation

Objective: Levocetirizine is a long-acting potent nonsteroidal anti-inflammatory drug (NSAID) which has a very low solubility in Gastrointestinal (GI) fluids results in poor bioavailability after oral administration. The present investigation aimed to formulate and evaluate fast dissolving oral films containing levocetirizine to overcome solubility and bioavailability problems thereby to facilitate the convenience of paediatric and geriatric patients. Method: The inclusion complexes of levocetirizine with β-cyclodextrin were prepared. In vitro dissolution study was performed to fix the ratio with better dissolution rate. The selected inclusion complex was then utilized for the preparation of fast dissolving oral films by solvent casting method using sodium CMC/ chitosan as film-forming agents, sodium starch glycolate/crospovidone as super disintegrating agents. PEG 400 used as a plasticizer. Formulations (F1-F6) were prepared and evaluated for their physicochemical properties. In vitro disintegration, dissolution and permeation studies were also carried out.

Tea saponin-Zein binary complex as a quercetin delivery vehicle: preparation, characterization, and functional evaluation

In this study, in order to solve the application problems of poor water solubility and low bioavailability of quercetin, we prepared a nano-delivery system with core-shell structure by anti-solvent method, including a hydrophilic shell composed of tea saponin and a hydrophobic core composed of Zein, which was used to improve the delivery efficiency and biological activity of quercetin. Through the optimal experiments, the loading rate and encapsulation rate of nanoparticles reached 89.41 % and 7.94 % respectively. And the water solubility of quercetin is improved by 30.16 times. At the same time, the quercetin acted with Zein through non-covalent interaction and destroyed its spatial network through structural characterization, while tea saponin covered the surface of Zein through electrostatic interaction, making it change into amorphous state. In addition, the addition of tea saponin makes the nanoparticles remain stable under the changes of external environment. During simulating gastrointestinal digestion procedure, ZQTNPs has higher release rate and bioavailability than free quercetin. Importantly, ZQTNPs can overcome the limitations of a single substance through synergy. These results will promote the innovative development of quercetin precision nutrition delivery system.

Ferrous ascorbate non-effervescent floating mini-caplets as an oral iron supplement.

This research aimed to develop non-effervescent floating mini-caplets of Ferrous Ascorbate (FA) using low-density polymers to overcome the problems of poor bioavailability associated with immediate-release iron products.Methods:The excipients and method (melt granulation) were selected based on pre-and post-compression parameters in trial batches. The formulation was optimized by a full factorial 32 experimental design. An optimized formulation was evaluated for drug release kinetic, accelerated stability study, and in vivo study in healthy adult New Zealand female rabbits.Results:The optimized formulation F6 mini-caplets (42.5% FA, 45% Glyceryl palmitostearate asPrecirol, 10% polyvinyl pyrrolidone K-30, and 2.5% lactose) were found to have instant floating and 12h floating duration in 0.1N Hydrochloric acid (HCl) dissolution medium. In vitro drug release (diffusion mechanism) at 1h and 5h was 30-35% and 65-70%, respectively. It was found stable for three months under an accelerated stability study. In vivo study showed significantly increased serum iron levels and decreased unsaturated iron binding capacity (UIBC) in the test group (optimized formulation) compared to control and standard (immediate-release iron).Conclusion:Based on the in vitro and in vivo results, we conclude that non-effervescent floating FA mini-caplets have higher bioavailability compared to immediate release FA, which may be attributed to prolonged iron release at its absorption site due to their retention in the gastric region. Hence, non-effervescent floating FA mini-caplets may act as a potential approach for iron deficiency.

Photothermal Iron-Based Riboflavin Microneedles for the Treatment of Bacterial Keratitis via Ion Therapy and Immunomodulation.

Bacterial biofilm formation protects bacteria from antibiotics and the immune system, excessive inflammation further complicates treatment. Here, iron-based metal-organic framework (MIL-101)-loaded riboflavin nanoparticles are designed for the therapeutic challenge of biofilm infection and hyperinflammation in bacterial keratitis. Specifically, MIL-101 produces a thermal effect under exogenous near-infrared light irradiation, which synergizes with ferroptosis-like bacterial death induced by iron ions to exert an effective biofilm infection eradication effect. On the other hand, the disintegration of MIL-101 sustains the release of riboflavin, which inhibits the pro-inflammatory response of macrophage over-activation by modulating their phenotypic switch. In addition, to solve the problems of short residence time, poor permeability, and low bioavailability of corneal medication, the MR@MN microneedle patch is further prepared by loading nanoparticles into SilMA hydrogel, which ultimately achieves painless, transepithelial, and highly efficient drug delivery. In vivo and ex vivo experiments demonstrate the effectiveness of this approach in eliminating bacterial infection and promoting corneal healing. Therefore, the MRMN patch, acting as an ocular drug delivery system with the ability of rapid corneal healing, promises a cost-effective solution for the treatment of bacterial keratitis, which may also lead to a new approach for treating bacterial keratitis in clinics.

Potential analgesic effect of a novel cannabidiol nanocrystals powder for the treatment of neuropathic pain.

The current analgesics often prevent patients from getting effective treatment due to their adverse effects. Cannabidiol (CBD) is well tolerated, has few side effects and has been extensively investigated in analgesia. However, its oral bioavailability is extremely low. In order to solve this problem, we developed the cannabidiol nanocrystals (CBD-NC) in the earlier stage. In this study, we evaluated the nociceptive behaviours associated with neuropathic pain (NP) induced by the spared nerve injury (SNI) model. Assessment of pain threshold was evaluated by paw withdraw threshold (PWT) and paw withdrawal latency (PWL). The improving effect on the motor dysfunction was determined by rota-rod testing. To assess the neuroprotective effect, nerve demyelination and expression of peripheral myelin protein PMP22 were measured with myelin sheath staining and western blotting. Protein expressions in microglia of spinal cord were tested by western blot to explore the underlying mechanism. Compared with the CBD oil solution, CBD-NC significantly reduced mechanical allodynia and thermal hyperalgesia in rats. CBD-NC could improve motor dysfunction induced by SNI in rats, significantly reverse the demyelination and increase the expression of the marker protein of peripheral myelin. Underlying spinal analgesic mechanism of microglia and related factors were preliminarily confirmed. CBD-NC administration is an effective treatment for NP associated with SNI, and the analgesic effect of CBD-NC was significantly better than that of CBD oil sol. By contrast, CBD-NC has a fast-acting and long-term effect in the treatment of NP. Our study further supports the potential therapeutic effect of CBD-NC on NP. The absolute bioavailability of the CBD-NC intramuscular injection formulation can reach 203.31%, which can solve the problem of low oral bioavailability. This research evaluated the therapeutic effect of CBD-NC on NP associated with the SNI model for the first time. All available date showed that whatever the analgesic or neuroprotective effect of CBD-NC, it was significantly better than that of CBD oil sol., which was consistent with the results of the pharmacokinetic. This research supports the initiation of more trials testing the efficacy of CBD-NC for treating NP.

Inhibition of Cancer Stem-like Cells by Curcumin and Other Polyphenol Derivatives in MDA-MB-231 TNBC Cells.

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is highly aggressive. Despite an initial positive response to chemotherapy, most patients experience rapid disease progression leading to relapse and metastasis. This is attributed to the presence of breast cancer stem cells (BCSCs) within the tumor, which are characterized by self-renewal, pluripotency, and resistance mechanisms. Targeting BCSCs has become critical as conventional therapies fail to eradicate them due to a lack of specific targets. Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs. The use of curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects. The aim of this study was to evaluate the cellular and molecular effects of six synthetic compounds derived from the natural polyphenol epigallocatechin gallate (EGCG) (TL1, TL2) and curcumin derivatives (TL3, TL4, TL5, and TL6) on a TNBC mesenchymal stem-like cell line. The activity of the compounds against BCSCs was also determined by a mammosphere inhibition assay and studying different BCSC markers by Western blotting. Finally, a drug combination assay was performed with the most promising compounds to evaluate their potential synergistic effects with the chemotherapeutic agents doxorubicin, cisplatin, and paclitaxel. The results showed that compounds exhibited specific cytotoxicity against the TNBC cell line and BCSCs. Interestingly, the combination of the curcumin derivative TL3 with doxorubicin and cisplatin displayed a synergistic effect in TNBC cells.

Technology of Enrichment of A2 Dairy Products with Carrot Powder Carotinoids

Topicality. Milk is an available for consumption, popular and nutritious food product, which contains a variety of important macronutrients and biologically active compounds, including carotenoids. Carotenoids contained in food products have low bioavailability, solubility and stability. A high fat content and a unique fat composition of dairy products can be used in order to overcome the problem of low carotenoid bioavailability which is common to fruits and vegetables. Therefore, the usage of fortified dairy products can be a potential means of increasing the supplyof carotenoids to the human body. The aim of the article is to eleborate a technology for enriching A2 dairy products with carrot powder carotenoids. Experimental samples of A2 milk with a mass fraction of fat (3.2%) were produced: control (without additives); sample 1 (enriched with carrot powder in the amount of 10%); sample 2 (enriched with carrot powder in the amount of 20%). The carrot powder was added to milk, thoroughly mixed for 10 minutes, and subjected to homogenization under a pressure of 100-110 MPa, after which it was filtered. The carrot pulp separated during milk filtration, in the amount of 10 and 20% by weight of the product, was used to enrich yogurts. Research methods. Using standard methods, in experimental milk samples organoleptic, physico-chemical indicators were determined according to DSTU EN ISO 1211:2022 (Ukrainian Research and Training Centre for Problems of Standardisation, Certification and Quality, 2023), as well as microbiological indicators were defined according to DSTU 7357:2013 (Ministry of Economic Development of Ukraine, 2014), DSTU 7089:2009 (State Consumer Standard of Ukraine, 2011), and carotenoid content (by chemical method). Additionally, the change in the active acidity of yogurts during their storage was studied by the method of direct potentiometry. Results. It was established that the addition of carrot powder had a positive effect on organoleptic quality indicators of milk, and caused an increase in the protein mass fraction within their composition by 0.03–0.04%. When adding 10% of carrot powder, the concentration of carotenoids increased by 0.163 mg/100 ml, and when adding 20%, then by 0.553 mg/100 ml accordingly. In the case of applying homogenisation under high pressure, and when enriching milk with carrot powder, its microbiological stability was ensured. Enrichment of yogurts with carrot pulp led to a significant increase of dietary fibers content in their composition, and allowed to raise the pH level of the finished product. During the entire storage period, the active acidity of enriched yogurts was within the normal range. Conclusions and discussion. Enrichment of milk with carrot powder and using homogenisation under high pressure leads to an increase in the concentration of carotenoids in milk, which provides almost 5% of the daily needs.

Incorporation of efavirenz inclusion complex In Dissolvable Microneedle for enhanced effectiveness of intravaginal drug delivery: A proof of concept study

Efavirenz (EFV) is one of the first line treatments of HIV infection. EFV is one of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that can inhibit the responsible of reverse transcriptase enzyme for HIV replication. In oral administration, EFV exhibits low bioavailability (30–56 %) problem owing to its poor solubility (0.9 μg/mL). In this research, the poor solubility was overcome by formulating EFV as a complex inclusion (IC)with β-cyclodextrin (β-CD). Furthermore, considering the benefits of vaginal delivery, IC was further incorporated into dissolving microneedle systems (DMN) using polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) as biocompatible and biodegradable polymes. The results showed that EFV successfully formed IC by the change of the molecular shape with β-CD polymer, confirmed by FTIR and XRD. Importantly, the results showed that the formulation did not cause lysis and irritation on erythrocytes and blood vessels, showing the safety of this approach. Following its incorporation into DMN, IC-DMN could permeate the skin ex vivo as 78.70 ± 14.22 μg/cm3, which was about 3-times higher compared to DMN containing pure EFV and patch control. The in vivo pharmacokinetic study showed that the maximum plasma concentration of IC-DMN was 13.74 ± 2.48 μg/cm3, EFV-oral 6.27 ± 1,13 μg/cm3, vaginal gel 14.83 ± 3.65 μg/cm3. AUC values for each treatment was 147.33 ± 26.62 h μg/mL, 22.33 ± 4.03 h μg/mL, 63.33 ± 11.44 h μg/mL, respectively, indicating that the purpose of this study which was to increase the bioavailability of EFV was succefully achieved. Therefore, this combibation approach could be new alternative to HIV treatment using EFV in woman.

Formulation Development of Non-effervescent Floating Pellets of Dried Ferrous Sulphate by Extrusion- Spheronization Technique

Dried Ferrous Sulphate is commonly used as iron salt for the treatment of iron deficiency by oral route, but conventional products face the problems of poor bioavailability due to its carrier-mediated absorption in an upper gastrointestinal region with a lower residence time at the absorption site and gastrointestinal side effects due to immediate release of the entire dose of an irritant drug which requires higher dosage frequency and prolonged duration of treatment to replenish deficient iron. Gastroretentive floating pellets of Dried Ferrous Sulphate would overcome these problems and to develop them using extrusion-spheronization, various grades of HPMC, ETHOCELTM 100cp along with Gelucire® 43/01 were tried in preliminary batches. Further optimization was done using Central Composite Design by selecting the different ratios of Gelucire® 43/01 and ETHOCELTM 100cp to a drug as formulation variables and spheronization time and speed as process variables, each at 3 levels. PVP K-30 as a binder and Isopropyl alcohol as a solvent were used. Pellets were characterized for average pellet size by sieving, roundness by microscopy, drug content, % drug release in vitro, and floating behaviour. Std run 3 with Gelucire® 43/01 (1.8:1) and ETHOCELTM 100cp (1.6:1), spheronized at 2000 RPM for 5 minutes was considered an optimized formulation which yielded an average pellet size of 868 µm ± 30, pellet roundness of 0.93± 0.02, immediate floating and sustained release for 12 hours in 0.1 N HCl dissolution medium and formulation with these characteristics could result into increased utilization of iron from the administered dose with reduced side effects.

Solubility Enhancement of Poorly Water-Soluble Aceclofenac by Amalgamation Micronization and Solid Dispersion Techniques

Aceclofenac is a poorly aqueous soluble Biopharmaceutical Classification System (BCS) class II drug that has bioavailability problems after oral administration due to low aqueous solubility. There are numerous solubility modification approaches and they also have process limitations. Hence, the present research work aims to use two different solubility enhancement techniques (Micronization with Solid dispersion) simultaneously to counter individual limitations of techniques. The micronization technique increases the solubility of pure aceclofenac through increasing particle surface area, but it produces charged micronized material, leading to segregation and clumping of micronized material. Hence, micronized material handling during dosage form manufacturing is quite difficult. In the present research work, aceclofenac material is micronized by air jet mill to produce materials of below 25 μm size ranges. This micronized aceclofenac material is further encapsulated in a solid dispersion technique to produce amorphous aceclofenac materials. Solid dispersion of micronized aceclofenac was prepared by various techniques like physical kneading, solvent evaporation, melting and a combination thereof using different polymers (Polyox 301, HPMC, cetostearyl alcohol and glyceryl behenate). The prepared solid dispersion formulation (SD-31, SD-22, SD-23 and SD-30) exhibited an increase in the dissolution of aceclofenac as compared to pure aceclofenac. Various characterization techniques (Differential scanning calorimetry (DSC), X-ray Diffraction (XRD) and scanning electron microscope (SEM)) also reveal that aceclofenac crystallinity is significantly minimized in Solid dispersion formulation of SD-31, SD-22, SD-23 and SD-30. This selected solid dispersion (SD-31 and SD-22) also exhibited good stability (Photostability and stability at 40°C/75% RH after 3 months).

Simultaneous Improvements of Physicochemical Properties and Anti‐Microbial Activity of Berberine via Forming Salt with Gallic Acid

AbstractImplementing combination medication through crystal engineering technology receives increasing attention from researchers due to improvements in the clinical treatment effects as well as the physicochemical properties of the drug. Berberine (BER) is commonly used to treat gastroenteritis and bacterial diarrhea, with the problems of poor solubility and low oral bioavailability. Recently, it is found that gallic acid (GA) also has anti‐inflammatory and anti‐bacterial activities. Therefore, if the above‐mentioned two ingredients can be combined, it is possible to enhance the therapeutic effects and physicochemical properties of BER. Inspired by this, 8‐hydroxy‐7,8‐dihydroberberine (8H‐HBER) in this study is employed to react with gallic acid to yield BER gallate dihydrate (2BER‐2GA‐2 W). Furthermore, dissolution experiments demonstrate that the maximum apparent solubility (MAS) of 2BER‐2GA‐2 W in dilute hydrochloric acid solution medium (pH 1.2) has increased by 7 times compared to the commercial form of BER, because of avoiding the common‐ion effect. Moreover, 2BER‐2GA‐2 W has also obviously enhanced stability relative to the commercial form of BER. In addition, 2BER‐2GA‐2 W has a better inhibitory effect on Staphylococcus aureus (S. aureus) relative to the commercial form of BER. Hence, 2BER‐2GA‐2 W will be a promising solid‐state form of BER for its further development.

Gallic Acid-Based Hydrogels for Phloretin Intestinal Release: A Promising Strategy to Reduce Oxidative Stress in Chronic Diabetes.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia caused by abnormalities in insulin secretion and/or action. In patients with diabetes, complications such as blindness, delayed wound healing, erectile dysfunction, renal failure, heart disease, etc., are generally related to an increase in ROS levels which, when activated, trigger hyperglycemia-induced lesions, inflammation and insulin resistance. In fact, extensive cell damage and death occurs mainly due to the effect that ROS exerts at the level of cellular constituents, causing the deterioration of DNA and peroxidation of proteins and lipids. Furthermore, elevated levels of reactive oxygen species (ROS) and an imbalance of redox levels in diabetic patients produce insulin resistance. These destructive effects can be controlled by the defense network of antioxidants of natural origin such as phloretin and gallic acid. For this reason, the objective of this work was to create a nanocarrier (hydrogel) based on gallic acid containing phloretin to increase the antioxidant effect of the two substances which function as fundamental for reducing the mechanisms linked to oxidative stress in patients suffering from chronic diabetes. Furthermore, since the bioavailability problems of phloretin at the intestinal level are known, this carrier could facilitate its release and absorption. The obtained hydrogel was characterized using Fourier transform infrared spectroscopy (FT-IR). Its degree of swelling (a%) and phloretin release were tested under pH conditions simulating the gastric and intestinal environment (1.2, 6.8 and 7.4). The antioxidant activity, inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a free radical source, was evaluated for four hours. All results showed that gallate hydrogel could be applied for releasing intestinal phloretin and reducing the ROS levels.

Polymeric nanomaterials encapsulating fluorescent polyindole-nido- carborane: design, synthesis and biological evaluation.

The water-soluble nido-carborane was prepared by alkali treatment of o-carborane. A polymer PInd containing a polyindole structure was synthesized and employed to label the modified o-carborane. Subsequently, four polymeric nanomaterials were synthesized with the objective of encapsulating them in order to enhance its bioavailability. The experimental results showed that the fluorescent complex encapsulated by the pH-sensitive polymer A had the best UV absorption and fluorescence intensity, and thus A-PInd-C was chosen for subsequent experiments. The Transmission electron microscopy images revealed that the compounds exhibited a rounded internal morphology, with the layers exhibiting a tightly stacked arrangement. The AFM imaging revealed that the surface of the sample exhibited a relatively uniform and smooth appearance. In vitro release experiments conducted under acidic conditions demonstrated that A-PInd-C was released in a predominantly linear manner, with a maximum release rate of 80% observed within 48h. Cellular imaging experiments showed that the compound could enter HeLa and HCT-116 cells and was mainly distributed around the nucleus, especially in the acidic environment. The results of the cell proliferation toxicity experiments demonstrated that A-PInd-C exhibited inhibitory effects on HeLa, PC-3 and L02 cells. Among these, the inhibitory effect on PC-3 cells was the most pronounced, reaching up to 70%. In conclusion, this paper solves the problem of poor bioavailability of carborane by improving the boron containing compounds and also makes the system have potential for Boron neutron capture therapy.

Neuroprotective effect and preparation methods of berberine.

Berberine (BBR) is a natural alkaloid, which has played an important role in the field of medicine since its discovery in the late 19th century. However, the low availability of BBR in vivo prevents its full effect. In recent years, a large number of studies confirmed that BBR has a protective effect on the nervous system through various functions, yet the issue of the inability to systematically understand the protection of BBR on the nervous system remains a gap that needs to be addressed. Many existing literature introductions about berberine in neurodegenerative diseases, but the role of berberine in the nervous system goes far beyond these. Different from these literatures, this review is divided into three parts: preparation method, mechanism, and therapeutic effect. Various dosage forms of BBR and their preparation methods are added, in order to provide a reasonable choice of BBR, and help to solve the problem of low bioavailability in treatment. More importantly, we more comprehensively summarize the mechanism of BBR to protect the nervous system, in addition to the treatment of neurodegenerative diseases (anti-oxidative stress, anti-neuroinflammation, regulation of apoptosis), two extra mechanisms of berberine for the protection of the nervous system were also introduced: bidirectional regulation of autophagy and promote angiogenesis. Also, we have clarified the precise mechanism by which BBR has a therapeutic effect not only on neurodegenerative illnesses but also on multiple sclerosis, gliomas, epilepsy, and other neurological conditions. To sum up, we hope that these can evoke more efforts to comprehensively utilize of BBR nervous system, and to promote the application of BBR in nervous system protection.