Low Solubility Drugs Research Articles

Zn(II)-Curcumin Complexes-Based Anticancer Agents.

There is a great deal of research interest in the design of alternative metallodrugs to Pt(II)-derivatives for cancer treatment. The low solubility of such drugs in biological mediums leading to poor bioavailability is the major hurdle of several metal-based anticancer agents. These issues have recently been addressed by designing bio-active ligands based on metal-containing anticancer agents. Conjugating with bioactive ligands has significantly improved the bioavailability of the metallodrugs and their cancer cell targeting ability. One such naturally available bioactive ligand is curcumin. Until recently, several curcumin-based anticancer metallodrugs have been developed and successfully demonstrated for their anticancer studies. In this article, we aim to highlight, the synthesis, structure, and anticancer properties of various Zn(II)-curcumin-based coordination complexes. The effect of introducing different functional groups, targeting ligands, and photo-active ligands on the anticancer potential of such complexes has been mentioned in detail. The current status and future perspective on curcumin-based metallodrugs for cancer treatment have also been stated.

Inhibition of HIV-1 infection with curcumin conjugated PEG-citrate dendrimer; a new nano formulation

BackgroundNano-drug delivery systems have become a promising approach to overcoming problems such as low solubility and cellular uptake of drugs. Along with various delivery devices, dendrimers are widely used through their unique features. PEG-citrate dendrimers are biocompatible and nontoxic, with the ability to improve drug solubility. Curcumin, a naturally occurring polyphenol, has multiple beneficial properties, such as antiviral activities. However, its optimum potential has been significantly hampered due to its poor water solubility, which leads to reduced bioavailability. So, the present study attempted to address this issue and investigate its antiviral effects against HIV-1.MethodThe G2 PEG-citrate dendrimer was synthesized. Then, curcumin was conjugated to it directly. FTIR, HNMR, DLS, and LCMS characterized the structure of products. The conjugate displayed an intense yellow color. In addition, increased aqueous solubility and cell permeability of curcumin were achieved based on flow cytometry results. So, it could be a suitable vehicle for improving the therapeutic applications of curcumin. Moreover, cell toxicity was assessed using XTT method. Ultimately, the SCR HIV system provided an opportunity to evaluate the level of HIV-1 inhibition by the curcumin-dendrimer conjugate using a p24 HIV ELISA kit.ResultsThe results demonstrated a 50% up to 90% inhibition of HIV proliferation at 12 μm and 60 μm, respectively. Inhibition of HIV-1 at concentrations much lower than CC50 (300 µM) indicates a high potential of curcumin-dendrimer conjugate against this virus.ConclusionThereby, curcumin-dendrimer conjugate proves to be a promising tool to use in HIV-1 therapy.

Mechanisms of drug release from a melt-milled, poorly soluble drug substance

Increasing the dissolution kinetics of low aqueous soluble drugs is one of the main priorities in drug formulation. New strategies must be developed, which should consider the two main dissolution mechanisms: surface reaction and diffusion.One promising tool is the so-called solid crystal suspension, a solid dispersion consisting of purely crystalline substances. In this concept, reducing the drug particle size and embedding the particles in a hydrophilic excipient increases the dissolution kinetics. Therefore, a solid crystal suspension containing submicron drug particles was produced via a modified stirred media milling process. A geometrical phase-field approach was used to model the dissolution behavior of the drug particles.A carrier material, xylitol, and the model drug substance, griseofulvin, were ground in a pearl mill. The in-vitro dissolution profile of the product was modeled to gain a deep physical understanding of the dissolution process. The used numerical tool has the potential to be a valuable approach for predicting the dissolution behavior of newly developed formulation strategies.

Ascorbyl palmitate nanofiber-reinforced hydrogels for drug delivery in soft tissues

Nanofiber-based hydrogel delivery systems have recently shown great potential in biomedical applications, specifically due to their high surface-to-volume ratio of ultra-fine nanofibers and their ability to carry low solubility drugs. Herein, we introduce a visible light-triggered in situ-gelling drug vehicle (GAP Gel) composed of ascorbyl palmitate (AP) nanofibers and gelatin methacryloyl polymer. AP nanofibers form self-assembled structures through intermolecular interactions with a hydrophobic drug-loading core. We demonstrate that the hydrophilic periphery of AP nanofibers allows them to interact with other hydrophilic molecules via hydrogen bonds. The presence of AP nanofibers significantly enhances the viscoelasticity of GAP Gel in a concentration-dependent manner. Further, GAP Gel shows in vitro biocompatibility and sustained drug delivery efficacy when loaded with a hydrophobic antibiotic. Likewise, GAP Gel shows excellent in vivo biocompatibility when implanted in immunocompetent mice in various forms. Lastly, GAP Gels maintain cell viability when cultured in a 3D-environment over 7 days, establishing it as a promising and versatile hydrogel platform for the delivery of biotherapeutics.

Manifesting the Dasatinib-gallic acid co-amorphous system to augment anticancer potential: Physicochemical characterization, in silico molecular simulation, ex vivo permeability, and in vitro efficacy

Dasatinib (DAB) has been explored for repurposing in the treatment of breast cancer (BC) due to its known effectiveness in treating leukemia, in addition to its role as a tyrosine kinase inhibitor. Gallic acid (GA) was chosen as a co-former due to its anticancer potential in BC, as demonstrated in several previous studies. DAB is a low-solubility drug, which is a significant hurdle for its oral bioavailability. To address this limitation, a DAB and GA co-amorphous (DAB-GA-CA) system was developed using liquid-assisted grinding and ball mill technology to enhance solubility, bioavailability, and anti-tumor efficacy. Physical characterization investigation revealed that the emergence of the halo diffractogram in PXRD, single glass transition temperature (Tg) value at 111.7 °C in DSC thermogram, and irregularly shaped blocks with loose, porous surfaces in SEM analysis indicated the formation of the DAB-GA-CA system at 1:1 M ratio. Furthermore, FTIR, Raman spectroscopy, in-silico molecular docking, and molecular dynamic studies confirmed the intermolecular hydrogen connections between DAB and GA. Moreover, the outcomes of the ligands (DAB and GA) and receptors (BCL-2, mTOR, estrogen receptor, and HER-2) docking studies demonstrated that both DAB and GA could interact with those receptors, leading to preventive action on BC cells. Additionally, the solubility and dissolution rate significantly improved at pH 6.8, and the permeability study indicated that DAB-GA-CA showed 1.9 times higher apparent permeability compared to crystalline DAB. Furthermore, in vitro cytotoxicity assessments of the DAB-GA-CA system revealed 3.42 times lower IC50 than free DAB. The mitochondrial membrane depolarization, apoptotic index, and reactive oxygen species formation in MCF-7 cells were also notably higher in the DAB-GA-CA system than in free DAB. Hence, this research suggests that the DAB-GA-CA system could substantially enhance oral delivery, solubility, and therapeutic efficacy.

Characterization of Alternative Starches and Its Effects on the In Vitro Dissolution of Capsules Containing Low Solubility Drugs (Ibuprofen and Nifedipine)

AbstractBiopharmaceutical applications of alternative starches (ASs), as excipients in capsules containing low solubility drugs (nifedipine and ibuprofen), from seeds of breadfruit (Artocarpus altilis), red‐jambo (Syzygium malaccense), jackfruit (Artocarpus heterophyllus Lam.), avocado (Persea americana), and yam rhizomes (Dioscorea spp.), are investigated. ASs are characterized by microscopic, thermal, and X‐ray diffraction (XRD) analysis. Dissolution profiles are traced and compared to the official starch (from corn) – soluble in hot water, particle size (2–32 µm) and amylose/amylopectin ratio (0.29–0.33). Microscopy analysis shows AS granules with tetrahedral and spherical/rounded shapes (average size of 21.45 µm). The amylose/amylopectin ratios of AS are: breadfruit (0.29–0.37), red‐jambo (0.25–0.29), jackfruit (0.28–0.37), avocado (0.33–0.43), and yam rhizomes (0.37–0.47). AS presents crystallinity patterns of types A, B, and C. Thermal analysis shows mass loss with dehydration – 303 and 373 K (30 and 100 °C) and degradation 525 and 626 K (252 and 353 °C). The release of nifedipine (≥80%, in 20 min) and ibuprofen (≥60%, in 30 min) are similar or superior to corn starch. Only AS obtained from avocado seeds fails to release nifedipine. This study contributes to the quality control of medicine and alternative bioproducts.

New Horizons in Antiretroviral Drug Delivery Systems for HIV Management.

Human Immunodeficiency Virus (HIV) infection is still a major global problem, whose drug treatment consists of prophylactic prevention and antiretroviral combination therapy for better pharmacological efficacy and control of circulating virus. However, there are still pharmacological problems that need to be overcome, such as low aqueous solubility of drugs, toxicity, and low patient adherence. Drug delivery technologies can be used to overcome these barriers. This review summarized the latest drug delivery systems for HIV treatment. Initially, an overview of the current therapy was presented along with the problems it presents. Then, the latest drug delivery systems used to overcome the challenges imposed in conventional HIV therapy were discussed. Articles published in the last 10 years were reviewed to obtain information on the innovations brought to HIV treatment. Delivery systems can improve the physicochemical properties of antiretroviral drugs, causing greater aqueous solubility, stability, and cellular and membrane permeability, which was reflected in the greater bioavailability of these drugs. However, more stability studies and techniques development are still needed to allow industrial scaling for large-scale production of drugs that use these technologies.

New mathematical model from dynamic dissolution rate tests

In vitro dissolution experiments are becoming increasingly complex attempting to replicate in vivo behavior. The objective of these new methods is to explore the behavior of low-solubility drugs. This is more relevant for drugs classified in subclasses 2a, 2b and 2c of the BCS, considering their pH-dependent solubility and dissolution characteristics.A novel mathematical approach using a modified double Weibull equation is proposed to model the dissolution and precipitation kinetics observed in two-stage and transfer dissolution experiments (dumping test). This approach demonstrates a high level of accuracy in fitting experimental data for two drugs BCS class 2a and two BCS class 2b, providing valuable insights into their dissolution behavior under different conditions.The results highlight the versatility of the proposed model in capturing complex dissolution phenomena, including rapid dissolution, precipitation, and redissolution. The ease of implementation in Excel, using the Solver tool, makes it a practical and accessible tool for pharmaceutical researchers.Overall, the study contributes to the development of more effective in vitro dissolution testing methods, facilitating the formulation and optimization of pharmaceutical products and potentially aiding in the establishment of in vitro-in vivo correlations (IVIVC).

Development of a solid dispersion system for polyvinyl alcohol nanofibers embedded with silicon dioxide particles via emulsion electrospinning for improved solubility of poorly water-soluble drugs

This study explored the development of solid dispersions of probucol (PBC), a poorly water-soluble drug, embedded within polyvinyl alcohol (PVA) nanofibers at a high concentration (30 %) via emulsion electrospinning. This study addressed the issues of low solubility and dissolution rates of such drugs by examining the incorporation of various types of silica particles—Aerosil 200 (A200), Sylisia 320 (SY320), Aerosil R972, and Sylophobic 100—as additives in oil-in-water emulsions. The results revealed that regardless of their hydrophilic or hydrophobic properties, silica particles preserved the amorphous state of PBC within the nanofibers without altering its crystallinity. Notably, all nanofibers embedded with silica particles demonstrated improved drug solubility compared to those without silica. This suggests that silica plays a role in mitigating the reduced solubility of drugs associated with their higher concentrations. Stability assessments of nanofibers embedded with A200 and SY320 under accelerated conditions revealed that A200 nanofibers preserved drug crystallinity and solubility, thus exhibiting superior storage stability. In contrast, SY320 nanofibers underwent drug crystallization, leading to a decrease in solubility upon storage. In conclusion, this study highlights the potential of silica particles in enhancing the solubility and stability of PBC in PVA nanofibers, suggesting that emulsion electrospinning with suitable silica additives is an effective strategy for developing advanced drug delivery systems for poorly water-soluble drugs.

Synthesis, Characterization, and Stability Optimization of Ibuprofen Cocrystals eEploying Various Hydrophilic Polymers.

Cocrystals are an efficient way for the delivery of low soluble drugs but when dissolved they rapidly disproportionate. To formulate the cocrystals in tablets, cocrystals must be stabilized. In this study ibuprofen-nicotinamide (IBU-NIC) cocrystals were synthesized initially by slow solvent evaporation and for bulk production by fast solvent evaporation techniques. The cocrystals were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectrophotometer (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and optical microscopy. The ibuprofen cocrystals showed greater solubility compared to the parent drug. Intrinsic dissolution data was utilized for efficacious screening of tablet formulations. Using hydrophilic polymers at a ratio of 6:1 (polymer to IBU-NIC cocrystal ratio), hydroxypropyl methylcellulose (F1), polyvinylpyrrolidone (PVP) K-30 (F2) and PVP K-90 (F3), three tablet formulations were prepared that stabilized cocrystals during dissolution. The drug release profiles after 60 minutes from formulations F1 (92.30), F2 (98.54), F3 (99.88) were all higher compared to the marketed brand BRUFEN® F, (79.61%) in a simulated intestinal media (p<0.001). Significant increase in the dissolution rate of cocrystal was observed with no phase change in all formulations.

Emerging Trends in Novel Drug Delivery Systems for the Effective Treatment of Oral Cancer

Background: The consumption of tobacco and alcohol has been correlated with the development of oral cancer, impacting various areas such as the mouth, lips, tongue, cheeks, and throat. This condition is marked by irregular cell proliferation involving intricate genetic and epigenetic alterations that drive tumorigenesis. Traditional treatments face limitations, necessitating a comprehensive multidisciplinary strategy. Novel Drug Delivery Systems [NDDS] offer groundbreaking therapeutic possibilities in addressing this complex health challenge. Objective: This review emphasizes the use of NDDS in the treatment of oral cancer Methods: The review entailed a comprehensive exploration of scientific databases and pertinent publications, encompassing studies conducted up to the current date sourced from PubMed, Science Direct, and Google Scholar Key. The search terms incorporated "oral cancer," "novel drug delivery system," "chemotherapy," "nanotechnology," and "conventional therapy." The chosen studies underwent meticulous assessment for methodological robustness and the importance of their findings. Results: NDDS serve an important role in targeted medication delivery by increasing drug bioavailability and reducing adverse effects. Addressing challenges such as low drug solubility, NDDS excels in sustained release methods, guaranteeing long-term therapeutic impact. Their versatility extends to the encapsulation of several anticancer drugs, giving a potential option for oral cancer treatment that is both efficacious and well-tolerated. This novel technique has the potential to transform treatment approaches, improving the efficacy and tolerability of oral cancer drugs. Conclusion: In oral cancer treatment, a spectrum of drug delivery systems is employed, encompassing conventional methods like oral and intravenous administration alongside innovative approaches such as vesicular systems, polymeric systems, and targeted strategies. Recent breakthroughs in oral cancer therapy, including immunotherapy [checkpoint inhibitors, CAR-T cell therapy] and gene therapy [siRNA, miRNA, CRISPR-Cas9], offer exciting prospects. These advancements hold the potential for enhanced therapeutic efficacy, minimized side effects, and personalized treatment options.

Development of single layer osmotic controlled release tablet for low soluble drug: Single Core Osmotic Pump (SCOP)

A novel Single Core Osmotic Pump (SCOP) pill has been created to administer high doses of the low solubility medication Rifaximin using osmosis. The formulations were evaluated using six comparative parameters: Q24 (total release after 24 hours), Q12 (total release after 12 hours), TL (lag time), RSQzero12 (R square of the zero-order equation for drug release in 12 hours), RR12 (in vitro release rate for 12 hours), and T80% (time required to deliver 80% of the drug). The drug release profile from osmotic devices shows that the choice of polymer and its concentration in the core formulation can significantly impact the release of the drug. Augmenting the osmogent quantity to an optimal level resulted in a substantial enhancement of Q12 and a notable improvement in the zero-order release pattern of rifaximin. In order to improve the bioavailability of the core formulation, an additive called citric acid was included. Citric acid has several properties that contribute to this enhancement, such as increased solubility of the active ingredient, the creation of a difference in osmotic pressure, regulation of the flow of the active ingredient, and making the composition containing the active ingredient more water-loving. Consequently, TL and T80% experienced a decline, whereas Q12 and RR12 saw a rise. The concentration of PEG 4000 in the semipermeable membrane of the SCOP was found to have a significant impact on TL, T80%, Q12, Q24, and RR12. Specifically, increasing the concentration of PEG 4000 led to a decrease in TL and T80%, while increasing Q12, Q24, and RR12. The optimal aperture diameter for achieving a zero-order release pattern was found to be 850 μm. This study also demonstrated that optimizing the thickness of SPM is crucial for achieving zero order kinetics. The invented SCOP technology has the potential to create a single layer osmotic controlled release tablet of a water insoluble medication with a high dosage.

Mechanistic Investigation of Enzyme Triggered Release from a Xyloglucan Matrix Tablet for Controlled Colonic Drug Delivery

The objective of this study was to investigate the mechanisms underlying drug release from a controlled colonic release (CCR) tablet formulation based on a xyloglucan polysaccharide matrix and identify the factors that control the rate of release for the purpose of fundamentally substantiating the concept and demonstrating its robustness for colonic drug delivery. Previous work demonstrated in vitro limited release of 5-aminosalicylic acid (5-ASA) and caffeine from these tablets in small intestinal environment and significant acceleration of release by xyloglucanase, an enzyme of the colonic microbiome. Targeted colonic drug delivery was verified in an animal study in vivo. In the present work, interaction of the xyloglucan matrix tablets with aqueous dissolution media containing xyloglucanase was found to lead to the spontaneous formation of a hydrated highly viscous gummy layer at the surface of the matrix which had a reduced drug content compared to the underlying regions and persisted with a nearly constant thickness that was inversely correlated to the enzyme concentration throughout the duration of the release process. Enzymatic hydrolysis of xyloglucan was determined to take place at the surface of the matrix leading to matrix erosion and a relation for the rate of enzymatic reaction as a function of bulk enzyme concentration and the concentration of dissolved xyloglucan in the gummy layer was derived. A mathematical model was developed encompassing aqueous medium ingress, matrix metamorphosis due to xyloglucan dissolution and matrix swelling, enzymatic hydrolysis of the polysaccharide and concomitant drug release due to matrix erosion and simultaneous drug diffusion. The model was fitted to data of reducing sugar equivalents in the medium reflecting matrix erosion and released drug amount. Enzymatic reaction parameters and reasonable values of medium ingress velocity, xyloglucan dissolution rate constant and drug diffusion coefficient were deduced that provided an adequate approximation of the data. Erosion was shown to be the overwhelmingly dominant drug release mechanism while the role of diffusion marginally increased at low enzyme concentration and high drug solubility. Changing enzyme concentration had a rather weak effect on matrix erosion and drug release rate as demonstrated by model simulations supported by experimental data, while xyloglucan dissolution was slow and had a stronger effect on the rate of the process. Therefore, reproducible colonic drug delivery not critically influenced by inter- and intra-individual variation of microbial enzyme activity may be projected.

Characterization of camphor: thymol or dl-menthol eutectic mixtures; Structure, thermophysical properties, and lidocaine solubility

The low solubility of drugs in aqueous media is a major problem for the pharmaceutical industry. Among the solutions proposed, the use of eutectic mixtures can be highlighted. In them, the components used can also increase the therapeutic advantages of the active principle. In this work, we analyzed the solubility of lidocaine in mixtures of camphor + thymol or dl-menthol. These binary eutectic solvents were also characterized. For all this, several NMR techniques were used and different thermophysical properties (density, speed of sound, refraction index, isobaric molar heat capacity, surface tension, and kinematic viscosity) were measured. The results indicated that the interaction of camphor with thymol was stronger than with dl-menthol, providing a more compact fluid. On the contrary, the steric hindrance was greater in the mixture with dl-menthol, giving rise to a more viscous liquid. Furthermore, the lidocaine was significantly more soluble (up to 540 times) in these mixtures than in water. The lidocaine showed the strongest interactions with thymol molecules, somewhat weaker with dl-menthol, and the weakest were with camphor ones.

Effect of novel surfactant protic ethanolamine based ionic liquids on the aqueous solubility and thermodynamic properties of acetaminophen

The solubility of poorly soluble drugs in aqueous media remains an obstacle in the pharmaceutical development process. Ionic liquids (ILs), with their remarkable solvent properties, have gained considerable attention as potential solubility enhancers for such drugs. In this context, surfactant protic ethanolamine-based ILs have emerged as a particularly promising class of compounds due to their unique dual functionality. This study explores the significant role of these novel solvents in improving drug solubility, focusing on their potential applications in pharmaceutical formulations. Acetaminophen (ACP), a widely used analgesic and antipyretic drug, often encounters solubility limitations that hinder its effective pharmaceutical applications. In the past few years, there has been a growing recognition of the potential of ILs (ionic liquids) as effective solvents. They offer promising prospects for enhancing the solubility of pharmaceutical substances in water-based solutions. This study investigates the enhancement of ACP solubility through the utilization of ILs. The solubilization behavior of ACP in the attendance of mono, bis and tris-(2-hydroxyethylammonium) octanoate systems is explored, highlighting the significant impact of different number of hydroxyethyl groups combinations on its solubility profile. Experimental results reveal that these ILs exhibit a remarkable ability to improve the solubility of ACP, making them attractive candidates for pharmaceutical formulations. The mechanisms underlying this enhancement are discussed, encompassing factors such as the ion-specific interactions, polarity, and hydrogen bonding capabilities of ionic liquids. Furthermore, the potential implications of utilizing ILs for enhancing the bioavailability and formulation versatility of ACP are considered. To accurately correlate the solubility data, various thermodynamic models were employed. Furthermore, to examine the observable thermodynamic characteristics of dissolution in the studied systems Van't Hoff and Gibbs equations were used. The findings indicated that the dissolution process in all co-solvents used was characterized by an endothermic nature and driven by enthalpy.

The Fabrication, Drug Loading, and Release Behavior of Porous Mannitol.

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray-antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer-Peppas kinetic model. In summary, the co-spray-antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials.

A remodeled ivermectin polycaprolactone-based nanoparticles for inhalation as a promising treatment of pulmonary inflammatory diseases

In recent years, ivermectin (IVM), an antiparasitic drug of low water solubility and poor oral bioavailability, has shown a profound effect on inflammatory mediators involved in diseases, such as acute lung injury, lung fibrosis, and COVID-19. In order to maximize drug bioavailability, polymeric nanoparticles can be delivered through nebulizers for pulmonary administration. The aim of this study was to prepare IVM-loaded polycaprolactone (PCL) nanoparticles (NPs) by solvent evaporation method. Box-Benkhen design (BBD) was used to optimize entrapment efficiency (Y1), percent drug release after 6 h (Y2), particle size (Y3), and zeta potential (Y4). A study was conducted examining the effects of three independent variables: PCL-IVM ratio (A), polyvinyl alcohol (PVA) concentration (B), and sonication time (C). The optimized formula was also compared to the oral IVM dispersion for lung deposition, in-vivo behavior, and pharmacokinetic parameters. The optimized IVM-PCL-NPs formulation was spherical in shape with entrapment efficiency (% EE) of 93.99 ± 0.96 %, about 62.71 ± 0.53 % released after 6 h, particle size of 100.07 ± 0.73 nm and zeta potential of -3.30 ± 0.23 mV. Comparing the optimized formulation to IVM-dispersion, the optimized formulation demonstrated greater bioavailability with greater area under the curve AUC0–t of 710.91 ± 15.22 μg .ml−1.h for lung and 637.97 ± 15.43 μg .ml−1.h for plasma. Based on the results, the optimized NPs accumulated better in lung tissues, exhibiting a twofold longer residence time (MRT 4.78 ± 0.55 h) than the IVM-dispersion (MRT 2.64 ± 0.64 h). The optimized nanoparticle formulation also achieved higher cmax (194.90 ± 5.01 μg/ml), and lower kel (0.21 ± 0.04 h−1) in lungs. Additionally, the level of inflammatory mediators was markedly reduced. To conclude, inhalable IVM-PCL-NPs formulation was suitable for the pulmonary delivery and may be one of the most promising approaches to increase IVM bioavailability for the successful treatment of a variety of lung diseases.

In vitro and In vivo Assessment of the Effect of Okra Gum Solid Dispersion in Atorvastatin Solubility

Background: Atorvastatin is BCS class II drug; it is lipid-lowering medication. Okra gum (OKG), from the pods of Abelmoschus esculentus, is natural product contain polymers having advantages over synthetic ones as it is safe, chemically inert, nonirritant, biodegradable, and does not require toxicological studies. Aim: This study aimed to assess the effect of okra gum solid dispersion in atorvastatin solubility. Method: The gum was extracted by hot water extraction and the dry extract was evaluated for percentage practical yield, flow properties, pH values and FTIR spectroscopy. Then solid dispersions with different drug to polymer ratios were prepared from OKG, and hydroxy propyl methyl cellulose (HPMC) by solvent evaporation method. Saturation solubility was tested for the solid dispersions prepared, the physical mixtures and atorvastatin. Tablets were prepared from solid dispersions with the highest saturation solubility, then tablets were tested and evaluated. Finally, in vivo test was done using Swiss albino mice and data were analyzed using one way Anova test followed by T test. Results: The content percent of atorvastatin in the solid dispersion prepared were 99,9- 100.1%, the tablets showed satisfactory physicochemical properties as 1.29% RSD in tablet weight variation, 24 min disintegration time, 5.24±0.457 Hardness and OKGSD tablets showed sustained release manner and 87% of drug released in 6 hrs. Lipid profile results showed significant decrease in total cholesterol level with marked decrease in LDL when using OKGSD tablets. Conclusion: It was concluded that OKG is promising excipient that can be used in dosage forms formulation to enhance solubility of low soluble drugs.

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP).

Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents an emerging paradigm for infectious disease control. In this scheme, a combination of a high efficacy and low solubility of anti-infection drugs permits the establishment of a pharmaceutical firewall in HIV-vulnerable groups over a long period. Although the structure-activity-relationship (SAR) of cabotegravir as an INSTI is known, the structural determinants of its low solubility have not been identified. In this work, we have integrated multiple experimental and computational methods, namely X-ray diffraction, solid-state NMR (SSNMR) spectroscopy, solution NMR spectroscopy, automated fragmentation (AF)-QM/MM and density functional theory (DFT) calculations, to address this question. The molecular organization of cabotegravir in crystal lattice has been determined. The combination of very-fast magic-angle-sample-spinning (VF MAS) SSNMR and solution NMR, as supported by AF-QM/MM and DFT calculations, permits the identification of structural factors that contribute to the low aqueous solubility of cabotegravir. Our study reveals the multitasking nature of pharmacophores in cabotegravir, which controls the drug solubility and, meanwhile, the biological activity. By unraveling these function-defining molecular features, our work could inspire further development of long-acting HIV PrEP drugs.

Preparation of polypeptide-metal complexes-coated Hosenkoside A and its inhibitory effect in cervical cancer

We reported the anti-cervical cancer effect of proprietary saponin content from seeds of Impatiens balsamina L., Hosenkoside A. Our study found that Hosenkoside A significantly promotes cell apoptosis and cell cycle arrest after administration, exhibiting anti-tumor effects. Then the transcriptome sequencing results after administration showed that Hosenkoside A had a significant inhibitory effect on Histone deacetylase 3 (HDAC3). After sufficient administration time, the inhibition of HDAC3 expression level leads to a significant decrease in lysine acetylation at histone 3 sites 4 and 9, blocking the activation of Signal transducer and activator of transcription 3 (STAT3) and achieving anti-tumor effects. In addition, we encapsulated Hosenkoside A into polypeptide metal complexes (PMC) to form slow-release spheres. This material breaks down in the tumor environment, not only does it solve the problem of low drug solubility, but it also achieves targeted sustained-release drug delivery. Under the same concentration of stimulation, the PMC complex group showed better anti-tumor effects in both in vitro and in vivo experiments.