Percentage Encapsulation Efficiency Research Articles

Study of the anti-cancer activity of a mesoporous silica nanoparticle surface coated with polydopamine loaded with umbelliprenin

A mesoporous silica nanoparticle (MSN) coated with polydopamine (PDA) and loaded with umbelliprenin (UMB) was prepared and evaluated for its anti-cancer properties in this study. Then UMB-MSN-PDA was characterized by dynamic light scattering (DLS), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and FTIR methods. UV-visible spectrometry was employed to study the percentage of encapsulation efficiency (EE%). UMB-MSN-PDA mediated cell cytotoxicity and their ability to induce programmed cell death were evaluated by MTT, real-time qPCR, flow cytometry, and AO/PI double staining methods. The size of UMB-MSN-PDA was 196.7 with a size distribution of 0.21 and a surface charge of −41.07 mV. The EE% was 91.92%. FESEM and TEM showed the spherical morphology of the UMB-MSN-PDA. FTIR also indicated the successful interaction of the UMB and MSN and PDA coating. The release study showed an initial 20% release during the first 24 h of the study and less than 40% during 168 h. The lower cytotoxicity of the UMB-MSN-PDA against HFF normal cells compared to MCF-7 carcinoma cells suggested the safety of formulation on normal cells and tissues. The induction of apoptosis in MCF-7 cells was indicated by the upregulation of P53, caspase 8, and caspase 9 genes, enhanced Sub-G1 phase cells, and the AO/PI fluorescent staining. As a result of these studies, it may be feasible to conduct preclinical studies shortly to evaluate the formulation for its potential use in cancer treatment.

Pectin nanoparticles loaded with nitric oxide donor drug: A potential approach for tissue regeneration

The process of wound healing and tissue regeneration involves several key mechanisms to ensure the production of new tissues with similar cellular functions. This study investigates the impact of pectin, a natural polysaccharide, and nebivolol hydrochloride (NBV), a nitric oxide (NO) donor drug, on wound healing. Utilizing ionotropic gelation, NBV-loaded pectin nanoparticles were developed following a 2231 full factorial design. The optimized formulation, determined using Design expert® software, exhibited an encapsulation efficiency percentage of 70.68%, zeta potential of −51.4 mV, and a particle size of 572 nm, characterized by a spherical, discrete morphology. An in vivo study was conducted to evaluate the effectiveness of the optimal formulation in wound healing compared to various controls. The results demonstrated the enhanced ability of the optimal formulation to accelerate wound healing. Moreover, histopathological examination further confirmed the formulation's benefits in tissue proliferation and collagen deposition at the wound site 15 days post-injury. This suggests that the developed formulation not only promotes faster healing but does so with minimal side effects, positioning it as a promising agent for effective wound healing and tissue regeneration.

Holistic Study Design Following Quality by Design Approach for Fabrication of Hybrid Polymeric Nanoparticulate Based Dry Powders as Carriers for Ciprofloxacin

Resistance to antibiotics such as Ciprofloxacin (CIP) is becoming a critical issue and needs to be addressed globally. CIP is widely used because of manifold uses; however, the long-term therapy poses serious health risks including FDA black box warnings such as tendinitis and peripheral neuropathy. Therefore, nanotechnology-based products can be an effective measure to improve therapeutic outcomes by maintaining the dose at the target site while reducing the dose-dependent toxicity. Biodegradable and biocompatible polymers, Chitosan (CS) and Hyaluronic acid (HA) were used in this work due to their diverse biological characteristics. A simple yet economical ionic gelation method was employed to synthesize nanoparticles with a plexus-like network; nanoplexes, followed by spray-drying to obtain the dry powders to improve stability. Quality by Design (QbD) approach was utilized during the study for robustness and standardization followed by Design of Experiment (DoE) for optimization in a holistic way. The mean particle size of the optimized powder sample was found to be 301.1 nm with a percentage encapsulation efficiency (% EE) of 78.8%. In-vitro dissolution studies corroborated the controlled release of CIP over 48 h. Also, mathematical kinetic modeling was applied to obtain thorough insight into the mechanism of drug release. Moreover, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were presented to be lower in the case of prepared dry powder as compared to CIP, stating that nanotechnology can improve antimicrobial activity.

Microencapsulation of Acalypha indica Linn. Extracts Using Chitosan-Polycaprolactone Blends

Polymer encapsulation is commonly adopted in drug delivery systems to form encapsulation that can assist in delivering active compounds to the targeted area. Acalypha indica (AI) crude extract was obtained from AI plants through ultrasound-assisted extraction. It is naturally unstable in the external environment and, thus, needs to be encapsulated to protect against volatility. Herein, this study emphasized the development of the encapsulations of AI extracts using a chitosan-polycaprolactone (PCL) blend by emulsion-solvent evaporation and freeze-dried methods. Four parameters for Al encapsulation were studied by fixing one parameter at a time. The percentage of encapsulation efficiency (EE%) was recorded as a response for each parameter. The study proceeded with central composite design (CCD) as the response surface methodology (RSM) optimization tool to study the interactions between the factors. Central points were taken from the preliminary data obtained in one-parameter experiments. The validation was carried out with two data of the highest and lowest EE% suggested by CCD. The highest EE% recorded was 98.70%, and the lowest EE% was 87.80%. The results showed a difference between predicted and experimental values at a percentage lower than 7.5%. Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM), particle size analyzer, and zeta potential were used to analyze the properties of selected microencapsulated samples. Overall, the encapsulation of AI extracts was successful and has the potential to be used in drug delivery.

Sertaconazole-PLGA nanoparticles for management of ocular keratitis

Ocular fungal infections can pose severe health conditions that may develop into vision impairment and blindness. Sertaconazole (STZ) is a widely used antifungal; however, its low aqueous solubility restricts its topical application for managing ocular keratitis. This investigation aimed to develop polymeric nanoparticles as delivery carriers to improve the ophthalmic availability of STZ for treating fungal keratitis. The impact of STZ solid dispersion incorporation within polymeric nanoparticles for in vitro drug release enhancement was also evaluated. STZ-laden PLGA NPs were formulated via nanoprecipitation technology, using a 24-full factorial layout to optimize the formulation. The formed nanoparticles were assessed for encapsulation efficiency percentage, hydrodynamic size, surface charge, and polydispersity index. The selected formula exhibited a particle size of 305.9 ± 4.36 nm, an entrapment efficiency (EE%) of 98.8 ± 0.008%, a surface charge of 22.57 ± 0.23 mV, and a low polydispersity index, indicating a uniform size distribution. Incorporating STZ in a solid dispersion form with PEG 2000 at a 1:3 w/w drug-to-carrier ratio increased the hydrodynamic size of the PLGA NPs. However, no significant variation in the entrapment efficiency percentage was recorded. The developed STZ-solid dispersion-loaded PLGA NPs have round-shaped structures. DSC and FTIR spectroscopy data indicated drug amorphization with successful loading within the PLGA matrix. Introducing the drug as a solid dispersion within PLGA NPs resulted in enhancing the rate of drug dissolution at initial time intervals, followed by a controlled drug release over 24 h. STZ-PEG2000-laden PLGA NPs enhanced permeability through rabbits’ corneas (Papp), 2.5-fold higher versus STZ-loaded PLGA NPs. The antimycotic activity of the developed formulation was tested against Candida albicans, and a 4-fold reduction in the MIC value was detected upon applying the nanoparticles’ formulation embedding STZ solid dispersion versus that containing the free drug. In conclusion, the formulation of solid dispersions of STZ loaded in PLGA nanoparticles may serve as a starting point for an efficient approach to the ocular delivery of hydrophobic medications and a viable setup for the upcoming research in animal models of fungal keratitis.

Chitosan functionalized doxorubicin loaded poly(methacrylamide) based copolymeric nanoparticles for enhanced cellular internalization and in vitro anticancer evaluation

Doxorubicin (Dox), a chemotherapeutic agent, encounters challenges such as a short half-life, dose-dependent toxicity, and low solubility. In this context, the present study involved the fabrication of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) bearing P(HPMA-s-APMA) copolymeric nanoparticles (P(HPMA-s-APMA) NPs) and their investigation for efficient delivery of Dox. Furthermore, the synthesized nanoparticles (NPs) were coated with chitosan (Cht) to generate positively charged nanoformulations. The prepared formulations were evaluated for particle size, morphology, surface charge analysis, percentage encapsulation efficiency (EE%), and drug release studies. The anticancer activity of Cht-P(HPMA-s-APMA)-Dox NPs was assessed in the HeLa cancer cell line. The prepared P(HPMA-s-APMA)-Dox NPs exhibited an average particle size of 240–250 nm. Chitosan decorated P(HPMA-s-APMA)-Dox NPs displayed a significant increase in particle size, and the zeta potential shifted from negative to positive. The EE% for Cht-P(HPMA-s-APMA)-Dox NPs was calculated to be 68.06 %. The drug release studies revealed a rapid release of drug from Cht-P(HPMA-s-APMA)-Dox NPs at pH 4.8 than pH 7.4, demonstrating the pH-responsiveness of nanoformulation. Furthermore, the cell viability assay and internalization studies revealed that Cht-P(HPMA-s-APMA)-Dox NPs had a high cytotoxic response and significant cellular uptake. Hence, the Cht-P(HPMA-s-APMA)-Dox NPs appeared to be a suitable nanocarrier for effective, and safe chemotherapy.

On chip synthesis of a pH sensitive gefitinib anticancer drug nanocarrier based on chitosan/alginate natural polymers

In this research, using a microfluidic chip, a nanocarrier for the anticancer drug gefitinib was synthesized. Chitosan and alginate natural polymers were utilized for the synthesis of the nanocarrier. The synthesis of the nanocarrier comprises the interaction of secondary amine functional groups of gefitinib molecules with carboxylate functional groups of alginate polymer to form the primary nucleus followed by the formation of the nanocarrier through the self-assembly of chitosan and alginate polymers on a fabricated microfluidic chip. The chip was fabricated by laser engraving poly(methyl methacrylate) polymer sheets. The nanocarrier was characterized by FT-IR, DLS, SEM, and TEM techniques. The synthesized nanocarrier had a size distribution of 5.30 ± 2.60 nm and the encapsulation efficiency percent was 68.4% in the optimum conditions. The loading efficiency was calculated as 50.2 mg g−1 of nanocarrier. Drug release studies showed that the nanocarrier is sensitive to pH and releases more gefitinib in acidic environments. Cytotoxicity of the synthesized nanocarrier was studied on the A549 non-small cell lung cancer, and the MTT test showed that the synthesized nanocarrier has a lower IC50 value than the free drug. Also, the cytotoxicity studies showed that the materials used for the synthesis of nanocarrier do not show significant cytotoxicity. Compared to the previously reported method, the developed microfluidic-assisted method showed advantages such as a faster synthesis procedure and comparable encapsulation efficiency and loading capacity.

IMPROVED SOLUBILITY OF CHOLECALCIFEROL AS BOVINE SERUM ALBUMIN (BSA) NANOPARTICLES

Objective: This study aims to report the optimum formula for BSA nanoparticles cholecalciferol (BSA-NP cholecalciferol), which can increase the solubility of cholecalciferol.Methods: BSA cholecalciferol nanoparticles was prepared by desolvation method with variations in solvent/non-solvent ratio, BSA concentration, pH of BSA solution, and cholecalciferol concentration. For this purpose, particle size, polydispersity index, and zeta potential were measured. Furthermore, the solubility test of the best BSA-NPs cholecalciferol formula was carried out.Results: The most optimal BSA nanoparticle cholecalciferol characterization results have a particle size of 166.6±50.3 nm, a zeta potential of-32.1 mV, and a percentage encapsulation efficiency (%EE) for cholecalciferol of 82.9±0.72%. The solubility of BSA-NP cholecalciferol is four times higher than that of pure cholecalciferol.Conclusion: The optimum formula for BSA-NP cholecalciferol with a solvent/non-solvent ratio of 1/2, a concentration of BSA of 2.5%, a BSA solution pH 6, and a cholecalciferol concentration of 0.1% will increase the solubility of cholecalciferol by four times compared to pure cholecalciferol.

Ferrous fumarate nanoliposomes: Formulation, characterization, and diffusion profiles

To assess the effect of cholesterol concentration in the preparation of ferrous fumarate nanoliposome toward its physicochemical properties and stability. Nanoliposomes were produced with cholesterol concentrations of 8, 12, and 16 mg using the thin film hydration method. The ultrasonic dispersion method and mini extruders were used to reduce the particle size. The nanoliposomes were evaluated for their physical properties, encapsulation efficiency, stability, and transport in the in vitro model of skin absorption. Formula 3 showed the smallest size results, with spherical multilamellar vesicle globules with a relatively dense matrix structure and even distribution between particles with a positive zeta potential value with an encapsulation efficiency percentage value of 61.67% ± 0.50 and a cumulative amount penetrated at the second hour of 442.077 mcg/cm2 ± 17.270 with a flux value of 14.575 mcg/cm−2/hour−1. Formulation 3 with higher cholesterol concentration showed better physical characteristics, encapsulation efficiency, and in vitro skin penetration compared to formulations with lower cholesterol concentration.

Formulation, optimization and evaluation of amisulpride-loaded niosomal intranasal gel for brain targeting.

Aim: To develop stable non-ionic surfactant vesicles containing amisulpride (AMS) to improve brain uptake via nose to brain mechanism. Methods: Niosomes were developed using a modified ethanol injection technique, optimized using 32 factorial design and evaluated for the vesicle size (VS), percent encapsulation efficiency (EE), zeta potential (ZP) and % cumulative drug release (%CDR). Results: Optimized niosomes (Span-60: cholesterol ratio 0:1) showed 191.4nm VS, 84.25% EE, -38.2ZP and 81.31% CDR. In situ gel with these niosomes displayed 78% CDR. TEM analysis revealed spherical niosomes. Pharmacokinetic and brain tissue distribution studies in rats showed enhanced plasma and brain concentrations, indicating successful brain targeting. Conclusion: This strategy demonstrates improved AMS permeation via the nasal cavity, enhancing bioavailability for treating schizophrenia.

Development and In Vitro Evaluation of Nanoparticles of Silymarin Using Central Composite Design

Silymarin is a phytoconstituent derived from the plant Silybum marianum with poor oral absorption and bioavailability but possesses hepatoprotective activity, anticancer activity, cardioprotective, neuroprotective, stabilizing, anti-inflammatory, and antioxidant activity. Therefore, the current work aims to develop a nanoformulation of silymarin to increase bioavailability, reduce dosing frequency, minimize toxicity, and improve patient compliance. Silymarin nanoparticles were created via the ionic gelation technique, employing chitosan and TPP as the primary polymers. A central composite design was employed for formulation optimization. Chitosan and TPP were employed as independent variables, while particle size and encapsulation efficiency were considered as dependent variables. The prepared nanoparticles were evaluated through entrapment efficiency, in vitro drug release, and drug-excipient interaction studies. Thirteen experiments were conducted using the experimental runs created by the central composite design. The average particle size was between 149nm and 294nm. The encapsulation efficiency percentage was between 65.4% and 87.3%. The polydispersity index had a value of 0.437. The zeta potential of the optimized formulation was determined to be 38.1 mV. The compatibility studies between the drug and excipients were confirmed using Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. The successful encapsulation of silymarin within the polymer core was verified through scanning electron microscopy analysis. The silymarin-loaded nanoparticles were observed to have a significant drug release of 98,942.43% over 24 hours. The outcomes of the study of Silymarin nanoparticles showed a substantial increase in the dissolution rate, which can be ascribed to the changed solubility properties of the drug. This result is consistent with the stated aim of improving drug absorption. Keywords: Silymarin, nanoformulation, central composite design.

Chitosan nanoparticles-based in vivo delivery of miR-155 modulates the Viral haemorrhagic septicaemia virus-induced antiviral immune responses in zebrafish (Danio rerio)

Viral haemorrhagic septicaemia virus (VHSV) is one of the highly pathogenic virus, which causes viral haemorrhagic septicaemia disease in both marine and freshwater fish. Micro RNA-155 (miRNA-155) is a multifunctional small non-coding RNA and it involves regulation of immune responses during viral infection. In this study, dre-miR-155 mimics were encapsulated into chitosan nanoparticles (CNPs). Resulted encapsulated product (miR-155-CNPs) was investigated for its immunomodulation role in zebrafish during experimentally challenged VHSV infection. Successful encapsulation of dre-miR-155 mimics into CNPs was confirmed through average nanoparticle (NPs) size (341.45 ± 10.00 nm), increased encapsulation efficiency percentage (98.80%), bound dre-miR-155 with chitosan, sustained release in vitro (up to 40%), and the integrity of RNA. Overexpressed miR-155 was observed in gills, muscle, and kidney tissues (5.42, 19.62, and 140.72-folds, respectively) after intraperitoneal delivery of miR-155-CNPs into zebrafish upon VHSV infection (miR-155-CNPs + VHSV). The miR-155-CNPs + VHSV infected fish had the highest cumulative survival (85%), which was associated with low viral copy numbers. The miR-155-overexpressing fish showed significantly decreased expression of ifnγ, irf2bpl, irf9, socs1a, il10, and caspase3, compared to that of the miR-155 inhibitor + VHSV infected fish group. In contrast, il1β, tnfα, il6, cd8a, and p53 expressions were upregulated in miR-155-overexpressed zebrafish compared to that of the control. The overall findings indicate the successful delivery of dre-miR-155 through miR-155-CNPs that enabled restriction of VHSV infection in zebrafish presumably by modulating immune gene expression.

Herpetetrone nanosuspensions enhance drug solubility and bioavailability to improve anti-hepatic fibrosis effects

The aim of this study was to enhance the dissolution rate and oral bioavailability of herpetetrone (HPT) by preparing nanosuspensions (NSs) and evaluate the changes in its anti-hepatic fibrosis effect. Herpetetrone nanosuspension (HPT-NS) was prepared using the ultrasound-precipitation technique, and characterised on the basis of mean diameter, zeta potential (ZP), encapsulation efficiency percent (EE%), scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD). In addition, the pharmacokinetics and anti-hepatic fibrosis activity were evaluated. HPT-NS prepared with the optimised formulation was found to be spherical with mean diameter of 177.48 ± 6.13 nm, polydispersity index (PDI) of 0.108 ± 0.002 and ZP of −17.28 ± 2.02 mV. The EE (m/m, %) was 83.25 ± 0.27. XRPD analyses confirmed that the amorphous state of HPT in HPT-NS remained unchanged. The dissolution rate of HPT-NS was significantly higher than that of HPT coarse suspensions (HPT-CSs). Following oral administration, C max and AUC0– t of HPT-NS showed a significant increase (p < 0.05). In vitro, HPT inhibited the proliferation of HSC-T6 cells and induced apoptosis by up-regulating the expression of Bax proteins and down-regulating the expression of Bcl-2 and TGF-β1 proteins. Compared with HPT-CS, HPT-NS exhibited a more pronounced anti-fibrotic effect. HPT-NS, as a new drug formulation designed to improve the solubility and bioavailability of the drug, shows promising potential in enhancing the anti-liver fibrosis effect.

Fabrication, Properties, and Stability of Oregano Essential Oil and Sodium Alginate-Based Wound-Healing Hydrogels.

The wound dressings fabricated by polymers and oregano essential oil (OEO) can be very effective as a hydrogel. The current study has been focused on fabricating the hydrogel membranes of oregano oil encapsulated as an antibacterial agent into sodium alginate (SA) solution by solvent casting method and then evaluated the antibacterial, antioxidant activity, and physicochemical performance of SA/OEO-based polymeric membranes. The polymeric interactions, surface morphology, water absorption capability, thermal stability, and encapsulation efficiency were investigated by FT-IR, SEM, swelling ratio, DSC, and encapsulation efficiency. The percentage encapsulation efficiency of essential oil was 40.5%. FTIR validated the presence of molecular interaction between individual components. SEM images showed a rough and porous appearance for hydrogel membranes. Moreover, DSC showed that the fabricated membranes were thermally stable. The inclusion of more content OEO decreased swelling ratios. The antioxidant test was carried out by DPPH assay and antibacterial test through disc diffusion method against microbes. The results revealed that membranes containing the highest content of OEO had more excellent antioxidant and antibacterial efficacy. Therefore, the polymeric membranes of sodium alginate loaded with oregano essential oil can be employed as an effective wound-healing candidate.

Fabrication, Characterization and in vitro Evaluation of Prednisolone Sustained Release Multiparticulate System for Colonic Targeting

Background: Prednisolone (PRD) is orally prescribed for inflammatory bowel syndrome (IBS) as the upper GIT is the main site of absorption; therefore, long-term PRD dosing decreases therapeutic effectiveness through systemic side effects. Objective: This work focused on formulating sustained-release alginate beads as a multiparticulate system for colon targeting using prednisolone (PRD) to be filled in an HPMC capsule. Methods: PRD beads were prepared by the ionotropic gelation technique using sodium alginate as the primary polymer and inulin, guar gum, and pectin as secondary polymers. In addition to the impact of polymer type and quantity, other factors were investigated: The CaCl2 concentration and tween 80 addition Thirteen formulations were successfully prepared, and their properties, such as bead size, morphology, percentage of encapsulation efficiency, yield, DL, in vitro release study in GIT buffer media, IBS media, SEM, and FTIR, were assessed. Results: The study showed that the beads were close in size, and the size was not an obstacle for loading the beads in HPMC capsules. Further, yield%, EE%, and DL% increased according to the bead’s content increase. Conclusions: The optimum formula was F3 that coated HPMC capsules with Eudragit S-100, which gave sustained release profiles in GIT and IBS simulating media, and F13 that could last the release in different pH media, pH 1.2, 6.8, and 7.4.

Microencapsulation of Sweet Potato Leaf (Ipomoea Batatas L.) Extract With Different Concentrations of Glucomannan Konjac and Maltodextrin Using Spray Drying Method

A large amount of phenolic compounds in sweet potato leaves are a potential source of antioxidants. However, polyphenol is sensitive under certain food processing, thereby needs innovation such as microencapsulation to maintain its stability. This study aimed to determine the encapsulation efficiency and characterization of microencapsulation of sweet potato leaf extract using maltodextrin (10% and 20%) combined with Konjac glucomannan (0.5%; 0.75% and 1%). The method used was spray drying using 120 oC inlet temperature. The result showed that the total phenolic compound of sweet potato leaves was 685.06 GAE mg/g extract. The antioxidant activity of sweet potato leaf extract with the DPPH method was 52.80% with an IC50 value of 26.73 ppm. The highest antioxidant activity of the microencapsulated powder sample (10% maltodextrin: 0.75% glucomannan) was 66.84% at a concentration of 100 ppm which had the greatest percent encapsulation efficiency (89.91%).The particle size distribution showed that encapsulated sweet potato leaf extract has a micro-size of around 0.296 µm (78.3%) with good homogeneity of the particle size which can be seen from the Pdi value of 0.304. Therefore, encapsulated sweet potato leaf with 0,75% glucomannan and 10% maltodextrin has the highest encapsulation efficiency and good characteristic.

Design, development, and evaluation of spray dried flurbiprofen loaded sustained release polymeric nanoparticles using QBD approach to manage inflammation

Spray-dried Flurbiprofen (FLB) loaded polymeric nanoformulation using Eudragit L 100 and Ethylcellulose. They were optimized and evaluated. This study determined drug release (%) and encapsulation efficiency (%) by developing a nanoparticulate system using the design of experiment (DoE) approach. FLB is slightly soluble in water; it dissolves slowly and has a low oral bioavailability. FLB-loaded polymeric nanoparticles were produced by solvent evaporation and Spray drying technology. In this research, nanoparticle formulation was prepared by screening and optimization by approaching two different statistical methods (Plackett-Burman and Central composite Designs). The polymeric nanoparticles were evaluated for various characteristics, including drug release, percentage of encapsulation efficiency, X-ray diffraction (X-RD), surface morphology, and Fourier transform infrared (FTIR) spectroscopy. Based on the X-RD analysis, it was found that the drug was successfully incorporated into the polymeric nanoparticles. As a result of nanoparticles containing FLB, % Drug release values were found to be nearly 85-90% increased while % EE was observed in the range of 79-89%. An excellent sustained release, i.e., 14 h, is possible by combining Ethylcellulose (EC) and Eudragit L 100 (ED-100) polymers. The results are beneficial in identifying the ideal formulation parameters for effective encapsulation. Abbreviations: FLB: Flurbiprofen; API: Active pharmaceutical ingredient; DR: Drug release; EE: Encapsulation efficiency; DoE: Design of experiment; X-RD: X-ray diffraction; FTIR: Fourier transform infrared spectroscopy.; PVA: Polyvinyl alcohol; EC: Ethylcellulose; EUGD: Eudragit L 100; NPs: Nanoparticles; PBD: Placket- Burman Design; CCD: Central Composite Design; CMV: Critical method variables; GIT: Gastrointestinal track; SLN: Solid lipid nanoparticles; NLC: Nanostructured lipid carriers; NSAID: Nonsteroidal anti-inflammatory drug; BCS: Biopharmaceutical classification system; PS: Particle size; PDI: Polydispersity Index; ZP: Zeta potential; FE-SEM: Field emission scanning electron microscopy; 2D: 2 Dimensional; 3D: 3 Dimensional

Ocular Delivery of Bimatoprost-Loaded Solid Lipid Nanoparticles for Effective Management of Glaucoma.

Glaucoma is a progressive optic neuropathy characterized by a rise in the intraocular pressure (IOP) leading to optic nerve damage. Bimatoprost is a prostaglandin analogue used to reduce the elevated IOP in patients with glaucoma. The currently available dosage forms for Bimatoprost suffer from relatively low ocular bioavailability. The objective of this study was to fabricate and optimize solid lipid nanoparticles (SLNs) containing Bimatoprost for ocular administration for the management of glaucoma. Bimatoprost-loaded SLNs were fabricated by solvent evaporation/ultrasonication technique. Glyceryl Monostearate (GMS) was adopted as solid lipid and poloxamer 407 as surfactant. Optimization of SLNs was conducted by central composite design. The optimized formulation was assessed for average particle size, entrapment efficiency (%), zeta potential, surface morphology, drug release study, sterility test, isotonicity test, Hen's egg test-chorioallantoic membrane (HET-CAM) test and histopathology studies. The optimized Bimatoprost-loaded SLNs formulation had an average size of 183.3 ± 13.3 nm, zeta potential of -9.96 ± 1.2 mV, and encapsulation efficiency percentage of 71.8 ± 1.1%. Transmission electron microscopy (TEM) study revealed the nearly smooth surface of formulated particles with a nano-scale size range. In addition, SLNs significantly sustained Bimatoprost release for up to 12 h, compared to free drug (p < 005). Most importantly, HET-CAM test nullified the irritancy of the formulation was verified its tolerability upon ocular use, as manifested by a significant reduction in mean irritation score, compared to positive control (1% sodium dodecyl sulfate; p < 0.001). Histopathology study inferred the absence of any signs of cornea tissue damage upon treatment with Bimatoprost optimized formulation. Collectively, it was concluded that SLNs might represent a viable vehicle for enhancing the corneal permeation and ocular bioavailability of Bimatoprost for the management of glaucoma.

Vitamin E modified polyamidoamine dendrimer for piperine delivery to alleviate Aβ1–42 induced neurotoxicity in Balb/c mice model

In Alzheimer’s disease (AD), amyloid beta (Aβ1-42) aggregate formation and neurofibrillary tangles are major pathological hallmarks which are related to neurodegeneration in the brain. To alleviate Aβ1-42 fibrils toxicity vitamin E derivative tocopheryl polyethylene glycol succinate (TPGS) was conjugated with polyamidoamine (PAMAM) dendrimer through carbodiimide reaction to synthesize TPGS-PAMAM. This TPGS-PAMAM was employed to entrap neuroprotective agent piperine (PIP) through an anti-solvent technique to prepare PIP-TPGS-PAMAM. The dendrimer conjugate was prepared to reduce Aβ1-42 induced neurotoxicity and increase acetylcholine levels in AD mice models. The synthesis of dendrimer conjugate was characterized through proton nuclear magnetic resonance (NMR) and Trinitrobenzene sulphonic acid assay (TNBS). Physical characterization of dendrimers conjugates were done through various spectroscopic, thermal and microscopy based techniques. PIP-TPGS-PAMAM showed 43.25 nm particle size with PIP percentage encapsulation efficiency of 80.35%. Further Aβ1-42 fibril disaggregation effect of nanocarrier was evaluated using Thioflavin–T (ThT) assay and circular dichroism (CD). The neuroprotection studies for PIP-TPGS-PAMAM was evaluated against neurotoxicity induced using Aβ1–42 intracerebroventricular (ICV) injected in Balb/c mice. The group of mice administered with PIP-TPGS-PAMAM exhibited an increase in the proportion of random alternations in T-maze test and novel object recognition test (NORT) exhibited an increase in working memory cognitive functions. The biochemical and histopathological analysis revealed PIP-TPGS-PAMAM treated groups enhanced acetylcholine levels, reduced ROS and Aβ1-42 content significantly. Our findings imply that PIP-TPGS-PAMAM enhanced memory and reduced cognitive deficit in mice brain induced by Aβ1-42 toxicity.

Evaluation of the anticancer potential of CD44 targeted vincristine nanoformulation in prostate cancer xenograft model: a multi-dynamic approach for advanced pharmacokinetic evaluation

The in vivo anticancer potential of vincristine (VC) loaded, thiolated chitosan-based nanoformulation (NFs) with an outer hyaluronic acid (VC-loaded in TCs-HA) coating was studied in prostate cancer (PC) xenograft in the immunosuppressed rat model induced by PC3 cell lines. Our previous study has already reported the in vitro efficacy of the said NFs. The ADMET Predictor (TM) Cloud version 10.4.0.5, 64-bit, was used to simulate VC's physicochemical and pharmacokinetic parameters. The percentage of encapsulation efficiency of VC by direct and indirect methods was 81.5 and 90%, respectively. Plasma samples from healthy rats showed improved pharmacokinetic and bioavailability profiles of NFs compared to VC injection via HPLC. The haemolytic analysis of NFs showed two times lesser toxicity to red blood cells. Xenograft rats showed maximum tumour volume up to 235 ± 0.02 mm3 with increased body weight, and it was reduced by 56 ± 0.01 to 107.3 ± 0.03 mm3 during the whole treatment by NFs compared to pure VC. The histopathology of the NFs group showed less malignancy with angiogenesis and significantly less metastasis to the liver and kidney. ELISA showed high expression of apoptotic biomarkers, including Bax, cleaved Caspase 3, and cleaved PARP, while the expression of BCL2, Caspase 3, COX-II, NFκB, and TNF-α was reduced. Immunohistochemical analysis also revealed that post-NF administration, cytoplasmic expressions of TNF-α and COX-II were reduced, as were nuclear expressions of NFκB. Thus, the prepared chemotherapeutic NFs were a comparatively potent oncolytic agent, safe with lesser off-target toxicity, and had an improved pharmacokinetic and bioavailability profile.