Lipophilic Drugs Research Articles

Attempts to Improve Lipophilic Drugs' Solubility and Bioavailability: A Focus on Fenretinide.

The development of numerous drugs is often arrested at clinical testing stages, due to their unfavorable biopharmaceutical characteristics. It is the case of fenretinide (4-HPR), a second-generation retinoid, that demonstrated promising in vitro cytotoxic activity against several cancer cell lines. Unfortunately, response rates in early clinical trials with 4-HPR did not confirm the in vitro findings, mainly due to the low bioavailability of the oral capsular formulation that was initially developed. Capsular 4-HPR provided variable and insufficient drug plasma levels attributable to the high hepatic first-pass effect and poor drug water solubility. To improve 4-HPR bioavailability, several approaches have been put forward and tested in preclinical and early-phase clinical trials, demonstrating generally improved plasma levels and minimal systemic toxicities, but also modest antitumor efficacy. The challenge is thus currently still far from being met. To redirect the diminished interest of pharmaceutical companies toward 4-HPR and promote its further clinical development, this manuscript reviewed the attempts made so far by researchers to enhance 4-HPR bioavailability. A comparison of the available data was performed, and future directions were proposed.

In Vitro Lipolysis Model to Predict Food Effect of Poorly Water-Soluble Drugs Itraconazole, Rivaroxaban, and Ritonavir

It is desirable to predict positive food effect of oral formulations due to food mediated dissolution enhancement of lipophilic drugs. The objective was to assess the ability of in vitro lipolysis to anticipate a positive food effect. Tested formulations included rivaroxaban and itraconazole, where some formulations, but not all, exhibit a positive food effect in vivo in humans. Amorphous solid dispersion formulations of ritonavir, which exhibit a negative food effect in vivo in humans, were also studied. Fe-lipolysis and Fa-lipolysis media representing fed and fasted intestinal conditions were used. Results show frequent agreement between in vitro lipolysis predictions and in vivo human outcomes. For rivaroxaban, food effect of unformulated active pharmaceutical ingredient (API) and products were correctly predicted where 2.5 mg and 10 mg strengths did not show any food effect; however, 20 mg did show a positive food effect. For itraconazole, all four products were correctly predicted, with Sporanox, Sempera, and generic capsules having a food effect, but Tolsura not having a positive food effect. For ritonavir, lipolysis predicted a positive food effect for API and Norvir tablet and powder, but Norvir products have negative food effect in vivo in humans. Overall, the lipolysis model showed favorable predictability and merits additional evaluation.

Quercetin-loaded transliposomal gel for effective management of skin cancer: In vitro and cell line efficacy studies

In this research work, Quercetin-loaded transliposomes (QUR-TL) were developed for dermal application against skin cancers. The utilization of nano-formulation for dermal application presents several notable advantages. Using an ethanol injection method followed by sonication, the QUR-loaded TL was developed and optimized by Box-Behnken Design (BBD). The optimized QUR-TL exhibited the vesicle size of 200.1 nm, polydispersity-index of 0.181, zeta potential of −31.89 mV and an entrapment efficiency of 82.1 %. The morphology of the optimized QUR-TL assessed by Transmission Electron Microscopy has revealed the spherical shape of the vesicles. In vitro release of QUR from QUR-TL was higher as compared to QUR-Suspn. Ex vivo skin permeation has shown ≈2-fold increased permeation of QUR from QUR-TL gel (QUR-TLG) as compared to QUR-conventional gel (QUR-CFG). This demonstrated a prolonged release pattern and an increased permeability of QUR from QUR-TLG. The QUR-TL has shown 1.3-fold higher antioxidant activity as compared to pure-QUR (QUR-SOL). The CLSM demonstrated an enhanced penetration of QUR-TLG, which was substantiated by the quantification of QUR during the dermatokinetics investigation. The QUR-TLG was evaluated for its cytotoxic potential against the B16F10 melanoma cells, which has shown lowest IC50 value (9.3 μM) as compared to QUR-CFG (16.8 μM) and QUR-SOL (23 μM). This suggested strong evidence of QUR indication for skin cancers. Conclusively, QUR-TLG has significantly (p < 0.05) targeted the deeper layers of skin and can be regarded as a promising carrier for topical application of QUR or other lipophilic drugs for the management of skin cancers.

An updated review on liposomes

Liposomes, tiny bubbles made from the same material as a cell membrane, are considered the most successful nanocarriers for drug delivery. They are biocompatible and stable, encapsulating both hydrophilic and lipophilic drugs and protecting them from degradation. Liposomes are the most commonly used drug delivery vehicles due to their high drug trapping capacity and efficiency. These offer controlled release, targeted drug delivery, increased therapeutic efficacy, and reduced dosing frequency. Liposome-based drug formulations have been approved for clinical use and are the subject of extensive research. Recent liposomal formulations aim to reduce toxicity and increase target site accumulation. With numerous advantages, liposomes prove their uniqueness in safe drug delivery in various areas of pharmacy and medicine. We will keep an eye on overall updated review on liposomes classification, their structural components, mechanism of action, stability, method of preparation, their evaluation tests and applications.

Phytosomes in herbal formulation: an updated review

Phytosomes, a phospholipid-based self-assembled delivery system, can improve oral bioavailability of polyphenolic compounds. These systems, prepared by reacting polyphenolic phytoconstituents with phospholipid, can enhance the passage of lipophilic herbal constituents across the lipid membrane. Phytosomes are used in various herbal drugs like Ginkgo biloba,Camellia sinensis. Recent advancements in phytosomes technology have led to the development of transdermal routes for delivering phytoconstituents. These products are increasingly used in dietary supplements for homeostatic management of inflammation, toxicities, cancers, and weight loss. This technique increases the hydrophilicity of highly lipophilic drugs, making them suitable for drug delivery and allowing hydrophilic phytoconstituents to cross biological membranes. Researchers are exploring the transdermal route as a potential way to deliver phytoconstituents, which are increasingly being used in dietary supplements for homeostatic management of various diseases. We will explore an updated review of Phytosomes in herbal formulation.

Benzoylation of Iota Carrageenan: Development of a Stable, Conductive, and Hydrophobic Drug Carrier with Reduced Toxicity and Improved Gel‐Forming Ability

AbstractIota carrageenan is characterized as a hydrocolloid, with the limitations of hygroscopicity and hydrophilicity. Here, each of these factors is addressed to enhance the stability, and hydrophobicity through the protection of highly reactive primary alcohol and the formation of stable, improved hydrophobic, and conductive gel for the loading of lipophilic drugs. The functionalized polymer is evaluated through the microscopic and scanning electron microscopy (SEM) image of the compounds, which confirm the confined nature of the functionalized polymer. Moreover, the values changed from compound 1 (iota carrageenan) to compound 2 (benzoyl liked iota carrageenan) included Log P (partition coefficient) from −0.97 to 0.90, calculated partition coefficient (cLog P) from −2.50 to 0.12, and total polar surface area (TPSA) from 214.1 to 208.57, which strongly suggest the enhanced hydrophobic character of functionalized polymers. The enhancement is further concluded by the loading of the lipophilic drug inside the core of functionalized polymer‐based gel. The enhanced loading of the drug clearly shows the improved hydrophobicity (56–86%) of the gel core of the functionalized compounds. In summary, a polymer with enhanced stability, hydrophobicity, conductivity, and capacity to make a more stable gel, with enhanced drug‐loading capability of water‐insoluble drugs, will be the best way to resolve the low bioavailability issue of the water‐insoluble drug.

Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal

BackgroundOsteoporosis is characterized by an imbalance in bone homeostasis, resulting in the excessive dissolution of bone minerals due to the acidified microenvironment mediated by overactive osteoclasts. Oroxylin A (ORO), a natural flavonoid, has shown potential in reversing osteoporosis by inhibiting osteoclast-mediated bone resorption. The limited water solubility and lack of targeting specificity hinder the effective accumulation of Oroxylin A within the pathological environment of osteoporosis.ResultsOsteoclasts’ microenvironment-responsive nanoparticles are prepared by incorporating Oroxylin A with amorphous calcium carbonate (ACC) and coated with glutamic acid hexapeptide-modified phospholipids, aiming at reinforcing the drug delivery efficiency as well as therapeutic effect. The obtained smart nanoparticles, coined as OAPLG, could instantly neutralize acid and release Oroxylin A in the extracellular microenvironment of osteoclasts. The combination of Oroxylin A and ACC synergistically inhibits osteoclast formation and activity, leading to a significant reversal of systemic bone loss in the ovariectomized mice model.ConclusionThe work highlights an intelligent nanoplatform based on ACC for spatiotemporally controlled release of lipophilic drugs, and illustrates prominent therapeutic promise against osteoporosis.

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820.

We have developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. The combination of chemotherapy and phototherapy has become a promising strategy to improve the therapeutic effect of chemotherapy drugs on solid tumors. IR820 can be used for photodynamic therapy (PDT), effectively converting near-infrared light (NIR) into heat and producing reactive oxygen species (ROS), causing damage to intracellular components and leading to cell death. In addition, PDT generates heat in near-infrared, thereby enhancing the sensitivity of tumors to chemotherapy drugs. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and -27.8 ± 0.42 mV, respectively. The encapsulation efficiency of SN38 and IR820 in SN38/IR820-Lipo@FSH liposomes were 90.2% and 91.5%, respectively, and their release was slow in vitro. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited better tumor-targeting ability and anti-ovarian cancer activity in vivo when compared with non-targeted SN38/IR820-Lipo. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Emphasis on Nanostructured Lipid Carriers in the Ocular Delivery of Antibiotics.

Drug distribution to the eye is still tricky because of the eye's intricate structure. Systemic delivery, as opposed to more traditional methods like eye drops and ointments, is more effective but higher doses can be harmful. The use of solid lipid nanoparticles (SLNPs) as a method of drug delivery has been the subject of research since the 1990s. Since SLNPs are derived from naturally occurring lipids, they pose no health risks to the user. To raise the eye's absorption of hydrophilic and lipophilic drugs, SLNs can promote corneal absorption and improve the ocular bioavailability of SLNPs. To address problems related to ocular drug delivery, many forms of nano formulation were developed. Some of the methods developed are, emulsification and ultra-sonication, high-speed stirring and ultra-sonication, thin layer hydration, adapted melt-emulsification, and ultrasonication techniques, hot o/w micro-emulsion techniques, etc. Results: Nanostructured lipid carriers are described in this review in terms of their ocular penetration mechanism, structural characteristic, manufacturing process, characterization, and advantages over other nanocarriers. Recent developments in ocular formulations with nanostructured bases, such as surfacemodified attempts have been made to increase ocular bioavailability in both the anterior and posterior chambers by incorporating cationic chemicals into a wide variety of polymeric systems.

Cubosomes: An Emerging and Promising Drug Delivery System for Enhancing Cancer Therapy.

Cancer and other diseases can be treated with cubosomes, which are lyotropic nonlamellar liquid crystalline nanoparticles (LCNs). These cubosomes can potentially be a highly versatile carrier with theranostic efficacy, as they can be ingested, applied topically, or injected intravenously. Recent years have seen substantial progress in the synthesis, characterization, regulation of drug release patterns, and target selectivity of loaded anticancer bioactive compounds. However, its use in clinical settings has been slow and necessitates additional proof. Recent progress and roadblocks in using cubosomes as a nanotechnological intervention against various cancers are highlighted. In the last few decades, advances in biomedical nanotechnology have allowed for the development of "smart" drug delivery devices that can adapt to external stimuli. By improving therapeutic targeting efficacy and lowering the negative effects of payloads, these well-defined nanoplatforms can potentially promote patient compliance in response to specific stimuli. Liposomes and niosomes, two other well-known vesicular systems, share a lipid basis with cubosomes. Possible applications include a novel medication delivery system for hydrophilic, lipophilic, and amphiphilic drugs. We evaluate the literature on cubosomes, emphasizing their potential use in tumor-targeted drug delivery applications and critiquing existing explanations for cubosome self-assembly, composition, and production. As cubosome dispersion has bioadhesive and compatible features, numerous drug delivery applications, including oral, ocular, and transdermal, are also discussed in this review.

Utilizing various plasma protein binding tools for free fraction determination of lipophilic and lipopeptide drugs

Utilizing various plasma protein binding tools for free fraction determination of lipophilic and lipopeptide drugs

Deformable Vesicles with Edge Activators for the Transdermal Delivery of Non-Psychoactive Cannabinoids.

Transdermal delivery of highly lipophilic molecules is challenging due to the strong barrier function of the skin. Vesicles with penetration enhancers are safe and efficient systems that could improve the transdermal delivery of non-psychoactive cannabinoids such as cannabidiol and desoxy-cannabidiol. In the last decades, research interest in desoxy-cannabidiol as a potent drug with anti-nociceptive properties has risen. Still, its scarce market availability poses a limit for both research and clinical applications. Therefore, it is necessary to improve the synthesis to produce sufficient amounts of desoxy-cannabidiol. Moreover, also the formulation aspects for this drug are challenging and require to be addressed to meet an efficient delivery to the patients. This work aimed to develop innovative phospholipid-based vesicles with propylene glycol (PG), oleic acid (OA), or limonene as edge activators, for the transdermal delivery of highly lipophilic drugs such as non-psychoactive cannabinoids. In particular, desoxy-cannabidiol was selected thanks to its anti-nociceptive activity, and its synthesis was improved enhancing the stereoselectivity of its synthon's production. Desoxy-cannabidiol was synthesized by Lewis acid-mediated condensation of p-mentha-2,8-dien- 1-ol and m-pentylphenol, improving the stereoselectivity of the first synthon's production. Transethosomes containing 20-50% w/w PG, 0.4-0.8% w/w OA, or 0.1-1% w/w limonene were optimized and loaded with cannabidiol or desoxy-cannabidiol (0.07-0.8% w/w, 0.6-7.0 mg/mL). Ex-vivo studies were performed to assess both the skin permeation and accumulation of the cannabinoids, as well as the penetration depth of fluorescein- loaded systems used as models. An enantioselective bromination was added to the pathway, thus raising the production yield of pmentha- 2,8-dien-1-ol to 81% against 35%, and the overall yield of desoxy-cannabidiol synthesis from 12% to 48%. Optimized transethosomes containing 0.6 mg/mL cannabinoids were prepared with 1:10 PG:lipid weight ratio, 0.54 OA:lipid molar ratio, and 0.3 limonene:lipid molar ratio, showing good nanometric size (208 ± 20.8 nm - 321 ± 26.3 nm) and entrapment efficiency (> 80%). Ex-vivo tests showed both improved skin permeation rates of cannabinoids (up to 21.32 ± 4.27 μg/cm2 cannabidiol), and skin penetration (depth of fluorescein up to 240 μm, with PG). Desoxy-cannabidiol was successfully produced at high yields, and formulated into transethosomes optimized for transdermal delivery. Loaded vesicles showed improved skin penetration of desoxy-cannabidiol, cannabidiol and a lipophilic probe. These results suggest the potential of these carriers for the transdermal delivery of highly lipophilic drugs.

Evaluation of Lipid Emulsion-Mediated Sequestration and Redistribution of the Highly Lipophilic Carbamazepine in the Plasma of Rats

Aim: The idea that intravenous lipid emulsion (ILE) may serve as a "reservoir" for lipophilic drugs has emerged in research as an intravascular "lipid sink" effect. Carbamazepine (CBZ) is a widely used anticonvulsant. This compound has a neutral and highly lipophilic structure and can easily cross body membranes. In this study, our hypothesis focused on the potential efficacy of ILE in modulating blood carbamazepine concentrations. Material and Methods: 22 adult Sprague-Dawley rats were divided into four groups. All groups received CBZ at a dose of 20 mg/kg orogastrically. The first group was the control group. In the second group (activated charcoal group), activated charcoal (AC) was administered orogastrically at a dose of 1 g/kg five minutes after orogastric administration of carbamazepine. The third group (lipid group) received ILE at a dose of 3 ml/kg/min at the fifth minute. The fourth group was the saline group, in which 16 ml/kg of 0.9% NaCl was infused at the fifth minute. Blood samples of 0.5 ml were collected at 0, 4, 8, and 24 hours. Plasma was separated by centrifugation (4000 rpm, 10 minutes) and stored at -80oC for determination of CBZ concentrations. An Agilent 6410B HP-1200 LC series (USA) liquid chromatography system was used for analysis. Quantitative analysis was performed in the multiple reaction mode with electrospray positive ionization (ES+). Results: At the 8th hour of orogastric CBZ administration, CBZ concentration was significantly lower in the activated charcoal group than in the lipid and saline groups (p: 0.021; p: 0.023; p&amp;lt;0.05, respectively). There was no significant difference in CBZ concentrations between the other groups at 8 hours (p&amp;gt;0.05). In the lipid group, the increase in CBZ plasma concentrations was statistically significant at 4 and 8 hours compared to 0 hours (p: 0.005; p: 0.005, respectively). Conclusion: In the lipid group, plasma CBZ concentrations increased at 4 and 8 hours in plasma samples from which lipids were separated by differential centrifugation. In the lipid group, no effects favoring drug-lipid sequestration on the plasma distribution of CBZ were observed.

Prospect of Gum Arabic-Cocoliposome Matrix to Encapsulate Curcumin for Oral Administration.

Curcumin is an antioxidant that can effectively eliminate free radicals. However, as its oral bioavailability is low, an effective delivery method is required. Phospholipid-based liposomes can encapsulate lipophilic drugs, such as curcumin, while liposome, cholesterol, and gum Arabic (GA) can enhance the internal and external stability of drug membranes. This present study used concentrations of cholesterol (Cchol) and GA (CGA), ranging from 0 to 10, 20, 30, and 40% as well as 0 to 5, 10, 15, 20, 30, and 40%, respectively, to encapsulate curcumin in a GA-cocoliposome (CCL/GA) matrix and test its efficacy in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). The absence of new characteristic peaks in the Fourier transform infrared (FTIR) spectra results indicate the presence of non-covalent interactions in the CCL/GA encapsulation. Furthermore, increasing the Cchol decreased the encapsulation efficiency (EE), loading capacity (LC), and antioxidant activity (IR) of the CCL/GA encapsulation but increased its release rate (RR). Conversely, increasing CGA increased its EE and IR but decreased its LC and RR. The two conditions applied confirmed this. Liposomal curcumin had the highest IR in SIF (84.081%) and the highest RR in SGF (0.657 ppm/day). Furthermore, liposomes loaded with 10% Cchol and 20% CGA performed best in SIF, while those loaded with 10% Cchol and 30% CGA performed best in SGF. Lastly, the CCL/GA performed better in SIF than SGF.

Potentiation of Brain Bioavailability Using Thermoreversible Cubosomal Formulation.

The aim of the present study was to develop and evaluate intranasal formulations of the thermoreversible fluoxetine cubosomal in situ gel. This gel was intended for permeation and bioavailability enhancement to target the brain effectively by bypassing the blood-brain barrier (BBB). Fluoxetine-loaded cubosomes were prepared by the homogenization method followed by the cold method approach to develop in situ gel. Fluoxetine-loaded cubosomes displayed a higher encapsulation efficiency (82.60 ± 1.25%) than fluoxetine. This might be due to the solubilizing activity of the polymer to cause partitioning of the lipophilic drug into the aqueous phase during the change from the cubic gel phase to cubosomes. In vitro analysis of fluoxetine-loaded cubosomal in situ gel showed a sustained release profile (93.22 ± 2.47%) due to limited diffusion of fluoxetine. The formation of strong affinity bonds of the drug with GMO (drug transporter) decreased the drug release in comparison to that with fluoxetine-loaded cubosomes (90.68 ± 1.74%). The ex vivo drug release profile revealed the drug release of 96.31 ± 2.88% by the end of 24 h. This is attributed to the higher capability of the intranasal cubosomal in situ gel to prolong the retention and enable better permeation through the nasal mucosa. In male Wistar rats, in vivo biodistribution studies for cubosomal in situ gel administered via the intranasal route at a dose of 3.5 mg/kg demonstrated an increase in pharmacokinetic parameters like the AUC (406 ± 75.35 μg/mL), Cmax (368.07 ± 0.23 μg/mL), Tmax (4 h), and t1/2 (14.06 h). The mucoadhesive nature of the in situ gel led to an increase in the residence time of the gel in the nasal mucosa. The biodistribution study of intranasal in situ cubosomal gel improved the bioavailability 2.21-fold in comparison to that with the cubosomal dispersion but 2.83-fold in comparison to that with the drug solution. Therefore, fluoxetine-loaded cubosomal in situ gel proved as a promising carrier for effective transportation of fluoxetine via the intranasal route with significant brain bioavailability.

Development and Optimization of Proniosomal Formulation of Irbesartan Using a Box-Behnken Design to Enhance Oral Bioavailability: Physicochemical Characterization and In Vivo Assessment.

This research work aimed to develop and evaluate proniosomes for the oral delivery of the lipophilic drug Irbesartan (IRB) to improve its solubility and bioavailability. Proniosomes of Irbesartan were formulated using a lipid, surfactant, and carrier by a slurry method. Based on the prepared preliminary trial batches and their evaluation, the formulation was optimized by employing a Box-Behnken design (BBD) in which concentrations of span 60 (X1), cholesterol (X2), and mannitol (X3) were used as three independent variables and the vesicular size (VS) (Y1), % entrapment efficiency (% EE) (Y2), and % cumulative drug release (% CDR) (Y3) were used as dependent variables. The optimized batch B1 was obtained from the BBD experiment after validation of checkpoint analysis, and their characterization was done for VS, % EE, % CDR, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. The optimized batch showed a VS of 199 ± 5.4 nm, a % EE of 99.25 ± 2.24%, and a % CDR of 97.36 ± 1.13% at 24 h. Scanning electron microscopy (SEM) study showed a smooth surface of batch B1. DSC and XRD studies indicated the amorphous nature of the proniosomal formulation. The proniosomal formulation showed increased solubility (2.65 ± 0.2 mg/mL) in phosphate buffer, pH 6.8, as compared to water (0.059 ± 0.02 mg/mL). The pharmacokinetic study in rats confirmed the increased bioavailability of the drug in optimized proniosomal formulation compared with its pure drug suspension. Cmax, Tmax, and AUC0-t of the drug also increased by 2-fold compared to those of drug suspension. Thus, in conclusion, the proniosomal formulation proved to be an efficient carrier for improved oral delivery of Irbesartan by improving the solubility and bioavailability of the drug.

Fabrication and evaluation of cross-linked nanogels of Dexibuprofen

The objective of this study was to design and develop an Agarose-based polymeric nanogel network system for solubility enhancement of a lipophilic drug, Dexibuprofen. Polymeric nanogels were synthesized through free radical polymerization where Agarose was cross-linked with 2-Acrylamido-2-methylpropane sulfonic acid (AMPS) in the presence of ammonium persulfate (APS) as an initiator and N, N’-Methylenebisacrylamide (MBA) as crosslinking agent. The resulting polymeric nanogels underwent a comprehensive characterization process including Fourier transform infrared (FTIR), particle size analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), and swelling studies to confirm the preparation of a stable polymeric nanogel system. FTIR spectral findings revealed that Agarose was chemically cross-linked with AMPS and confirmed the successful insertion of AMPS chains on the Agarose backbone. Particle size analysis revealed a diameter of 168 nm with a zeta potential of −9.91 mV, providing assurance of a stable polymeric nanogel system. SEM images depicted a highly porous surface. DSC and TGA results showed a more thermally stable network system than individual ingredients. Swelling studies revealed an increased swelling ratio of polymeric nanogels at phosphate buffer of pH 6.8 than acidic buffer of pH 1.2. Dexibuprofen was efficiently loaded into a polymeric nanogel system with a high entrapment efficiency of up to 80%. The solubility of the drug was enhanced when introduced to a polymeric nanogel formulation when compared to pure drug. The system reproducibility was evaluated through in vitro drug release and kinetic modeling of drug release. Toxicity studies confirmed the formulation’s effectiveness, showcasing the developed polymeric nanogels as a promising option for delivering lipophilic drugs, with outstanding physicochemical properties, improved solubility, and minimal oral toxicity.

Niosomal Drug Delivery System used in Tuberculosis

Niosomes are artificially manufactured vesicles made of Cholesterol and Non-ionic surfactant. Their capacity to encapsulate a broad variety of pharmaceuticals and shield them from deterioration has piqued interest in drug delivery. Niosomes have demonstrated a possible use in the administration of anti-tuberculosis medications. Worldwide, tuberculosis is a serious public health concern. Even with advances in science and technology, tuberculosis remains a persistent problem.Niosomes can encapsulate anti-TB drugs, protecting them from enzymatic degradation and allowing for sustained release. Research in this field is on-going, with scientists working on optimizing niosomal formulations for tuberculosis treatment. It's important to consult current scientific literature for the latest advancements. Some anti-tubercular drugs face challenges in terms of absorption and bioavailability. Niosomal delivery systems can help address these issues. While niosomal drug delivery systems show promise, it's crucial to note that they are still an area of active research and specific formulations and protocols may vary. Patients should always consult with their healthcare providers for the most appropriate and up-to-date treatment options for tuberculosis. Niosomes can encapsulate both hydrophilic and lipophilic drugs, offering advantages such as increased drug stability, prolonged circulation time, controlled release, and targeted delivery. They have applications in various fields including pharmaceuticals, cosmetics, and agriculture.&#x0D; Keywords: Tuberculosis, Niosomes, Drug delivery system

Therapeutic potential of procathepsin L-inhibiting and progesterone-entrapping dimethyl-β-cyclodextrin nanoparticles in treating experimental sepsis.

The pathogenic mechanisms of bacterial infections and resultant sepsis are partly attributed to dysregulated inflammatory responses sustained by some late-acting mediators including the procathepsin-L (pCTS-L). It was entirely unknown whether any compounds of the U.S. Drug Collection could suppress pCTS-L-induced inflammation, and pharmacologically be exploited into possible therapies. Here, we demonstrated that a macrophage cell-based screening of a U.S. Drug Collection of 1360 compounds resulted in the identification of progesterone (PRO) as an inhibitor of pCTS-L-mediated production of several chemokines [e.g., Epithelial Neutrophil-Activating Peptide (ENA-78), Monocyte Chemoattractant Protein-1 (MCP-1) or MCP-3] and cytokines [e.g., Interleukin-10 (IL-10) or Tumor Necrosis Factor (TNF)] in primary human peripheral blood mononuclear cells (PBMCs). In vivo, these PRO-entrapping 2,6-dimethal-β-cyclodextrin (DM-β-CD) nanoparticles (containing 1.35 mg/kg PRO and 14.65 mg/kg DM-β-CD) significantly increased animal survival in both male (from 30% to 70%, n = 20, P = 0.041) and female (from 50% to 80%, n = 30, P = 0.026) mice even when they were initially administered at 24h post the onset of sepsis. This protective effect was associated with a reduction of sepsis-triggered accumulation of three surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF) by 40%; Macrophage Inflammatory Protein-2 (MIP-2) by 45%; and Soluble Tumor Necrosis Factor Receptor I (sTNFRI) by 80%]. Surface Plasmon Resonance (SPR) analysis revealed a strong interaction between PRO and pCTS-L (KD = 78.2 ± 33.7 nM), which was paralleled with a positive correlation between serum PRO concentration and serum pCTS-L level (ρ = 0.56, P = 0.0009) or disease severity (Sequential Organ Failure Assessment, SOFA; ρ = 0.64, P = 0.0001) score in septic patients. Our observations support a promising opportunity to explore DM-β-CD nanoparticles entrapping lipophilic drugs as possible therapies for clinical sepsis.

Multifunctional polypeptide-based polymersome for chemophotothermal therapy of melanoma in vitro and in vivo

To date, combination therapy using chemo-photothermal therapy (Ch-PTT) has attracted tremendous interest due to its efficient ablation of cancerous cells. Furthermore, there are several advantages to using peptide-based nanocarriers for theranostic nanoplatforms, such as excellent biocompatibility and biodegradability, significant encapsulation efficacy for lipophilic drugs with negligible drug leakage, excellent stability, and excellent enzymatic degradation. In the current study, a multifunctional theranostic system based on polymersome (vesicular nanocarrier of self-assembled amphiphilic polymer) was developed for targeted Ch-PTT and x-ray CT imaging of melanoma cancer. For this purpose, using ring opening polymerization (ROP) of γ-benzyl l-glutamate-N-carboxyanhydride (LG-NCA) lipophilic polypeptide PLG (poly(γ-benzyl-l-glutamate) was synthesized and covalently linked to bifunctional COOH-PEG-NH2. Next, polypeptide-based polymersome nanocarier based on amphiphilc PEG-PLG was fabricated and co-encapsulated with hydrophilic gold nanorod (AuNR) and lipophilic curcumin (CUR) in aqueous core and lipophilic bilayer of polymersome (P-AuNR-CUR), respectively. Then, Sgc8-c aptamer were decorated on the polymersome surface (Apt-P-AuNR-CUR) for targeted delivery, and the size of P-AuNR-CUR and Apt-P-AuNR-CUR were determined using DLS device (174.3 ± 5.95 and 206 ± 52, respectively). NIR (near-infrared)-laser-triggered drug delivery release performance of multifunctional polymersome was demonstrated in both citrate and phosphate buffer saline. According to both in vitro and in vivo studies, NIR-responsive polymersomes possess remarkable therapeutic efficacy for Chemo-PTT in comparison to individual cancer therapy. Furthermore, the diagnostic capability of the designed nanoplatform was confirmed using in vivo CT scan imaging 6 h post-intravenous injection.