Percentage Entrapment Efficiency Research Articles

Preparation and characterization of azelnidipine-loaded D-α-tocopheryl polyethylene glycol succinate (TPGS) / solutol micelles

Azelnidipine is a calcium-channel antagonist classified as a “class 2” drug with high permeability and low aqueous solubility. It is used in the treatment of angina pectoris and hypertension without reflex tachycardia. Improvement of the solubility of azelnidipine and increasing drug’s bioavailability can be achieved through the drug encapsulation in solutol / D-α-tocopheryl polyethylene glycol succinate (TPGS) micelles. Six formulas were prepared by direct disso¬lution after using different amounts of solutol and TPGS. TPGS and solutol act as solubilizers, permeation enhancers, and P-glycoprotein inhibitors. The particle size, particle size distribution, zeta potential, and entrapment efficiency were determined. Depending on particle size and entrapment efficiency, formula #6 was selected and subjected to in vitro dilution stability and in vitro release studies. The results obtained showed that formula #6 was the best formula, with a high entrapment efficiency percentage equal to 86.5%±0.58% and a small particle size equal to 21.9±7.75 nm that did not change significantly after dilution up to 100-fold; a fact that reveals the high thermodynamic and kinetic stability of the optimum formula. The formula #6 release profile showed a controlled release of the drug from micelles when compared to plain drug release. Based on these results, polymeric nanomicelles are regarded as a promising delivery system for azelnidipine.

Epigallocatechin-3-gallate loaded proliposomal vesicles for management of traumatic brain injury: In-vitro and in-vivo evaluation

One of the primary causes of disability and mortality worldwide is traumatic brain injury (TBI). Oxidative stress is one of the main pathological cascades of TBI. Therefore, finding an effective antioxidant for TBI is a challenge. Several studies revealed that Epigallocatechin-3-gallate (EGCG) had neuroprotective properties, so it might play an important role in TBI. However, it has some drawbacks including instability that may lead to reduced efficacy which could be enhanced using nanoformulation. Consequently, this study aimed to design and optimize EGCG-loaded Proliposomes (EGCG-PLs) and to investigate the antioxidant effect against TBI in rats by modulating the Sirt1/Nrf2/HO-1 signaling pathway. EGCG-PLs were formulated by the slurry technique. Then, to choose the best formula, nanovesicles were assessed and optimized by the Box-Behnken Design to determine the effect of preparation factors on the formed vesicles. Following that, we used an animal model of TBI to compare the neuroprotective effects of the optimized formula to the free drug in vivo. To confirm the neuroprotective action, oxidative stress biomarkers were evaluated as well as histopathological examinations of different brain tissues were performed. The optimized EGCG-loaded PLs formula had a mean size of 150.63 ± 2.65 nm while the percentage of entrapment efficiency was 89.744 ± 0.89 %. The EGCG in vitro release from the optimized PLs formula was prolonged in comparison with the free EGCG. The optimized formula showed a superior antioxidant effect compared to its free counterpart as it significantly decreased MDA and increased the endogenous antioxidants, SOD, and GSH, of brain tissues in addition to activation of the Sirt1/Nrf2/HO-1 signaling pathway. Furthermore, amelioration of histopathological alterations induced by TBI in brain tissues was more prominent with EGCG-PLs treatment. To conclude, all outcomes point to a potential enhancement in the efficacy of EGCG when prepared in PLs in combating TBI.

Fabrication of prostructured spanlastics gel for improving transdermal effect of dapagliflozin: In vitro characterization studies and in vivo antidiabetic activity

Dapagliflozin is a recently approved glucose-lowering agent for the management of type II diabetes mellitus. Low solubility and stability lead to its poor oral bioavailability. Prostructured spanlastic gel is very less hydrated preform of spanlastic vesicles. Therefore, the aim of this study was to explore the potential of prostructured spanlastic gel for enhancing both drug stability and transdermal delivery. The prostructured spanlastic gel formulations were fabricated by coacervation phase separation method, using Span 60 together with Tween 80 or Myrj 52 as an edge activator. Formulations were characterized for drug content, in vitro release and ex vivo skin permeability. Verification of vesicular form was assessed by hydration and the resultant formulations were characterized. Selected formulations were assessed for morphology, interaction of drug with other components, stability and antidiabetic activity. Drug content percentage of spanlastic gels was found to be in range 98.1±1.9 to 94.2±2.0%. Significant (p < 0.05) increase in drug release rate was observed when edge activator concentration was greater than 30%. Tween 80 containing formulations exhibited higher skin permeation than Myrj 52 containing ones at the same concentration of edge activator. Spanlastic vesicles were formed by hydration and had entrapment efficiency percentages ranging from 65.06±0.87% to 40.36±0.95%, mean vesicle sizes ranging from 136.1 nm to 56.52 nm and zeta potential values ranging from –29.7 mV to –6.94 mV. The morphologic examination verified formation of nanovesicular form. Thermal analysis and FT-IR confirmed encapsulation of drug inside spanlastic vesicles. Spanlastic gels showed higher stability and skin permeability when compared to vesicular form in hydroalcoholic gel. Spanlastic gels also showed prolonged hypoglycemic effect and blood glucose level reached below 135±4.7 mg/dL after 24h, when compared to hydroalcoholic gel (273±3 mg/dL) and oral suspension (271±5 mg/dL). In conclusion, spanlastic gel could be a promising carrier for enhancing transdermal delivery of dapagliflozin, offering both sustained and enhanced antidiabetic activity.

Sustained release delivery of favipiravir through statistically optimized, chemically cross-linked, pH-sensitive, swellable hydrogel.

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir.

Enhancement of Physical Appearance, Skin Permeation, and Odor Reduction Using Liposome of Hydrolyzed Salmon Collagen for Cosmetic Products

Hydrolyzed collagen (HC) derived from salmon (Oncorhynchus nerka) skin possesses properties that can nourish the skin, and it is one of the active ingredients used in cosmeceutical products for moisturizing the facial skin. However, HC solution gives off a fishy odor and it is gray in color that makes the product unacceptable for cosmetic purposes. This study aimed to use liposome-encapsulated hydrolyzed salmon collagen to improve its physical appearance, skin permeation, and eliminate the fishy odor. Two percent of HC and vitamin B3 (VitB3) were used as active ingredients to incorporate into liposomes. Phosphatidylcholine, cholesterol, and Tween 80 at a suitable weight ratio of 8 : 2 : 1 produced nano-sized vesicles (170.6 ± 0.70 nm) with the highest percentage of entrapment efficiency (95.72 ± 2.00%) of VitB3 and (49.63 ± 1.74%) of HC. Skin permeation and odor detection of the HC-VitB3 liposome were studied using Franz’s diffusion cell and gas chromatography, respectively, and compared with HC-VitB3 solution. Subsequently, facial serums were formulated using HC-VitB3 liposomes and HC-VitB3 solutions, and a product satisfaction test was conducted with 100 volunteers to determine their preferred product. The results of the studies of HC-VitB3 liposome serum showed improved formulation appearance, enhanced skin permeation, and better odor elimination compared to the HC-VitB3 serum. Furthermore, seventy-three volunteers in the product satisfaction test preferred and selected the liposomal serum for its superior scent. From all the experimental results, it could be seen that liposomes can help increase skin penetration, and undesirable odors and colors can be masked by the appropriate lipid bilayer structure of liposomes.

Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma.

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16mg/ml) and sonication time (5, 10, 15min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.

Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study.

Metformin (MET), an antidiabetic drug, is emerging as a promising anticancer agent. This study was initiated to investigate the antitumor effects and potential molecular targets of MET in mice bearing solid Ehrlich carcinoma (SEC) as a model of breast cancer (BC) and to explore the potential of zein nanoparticles (ZNs) as a carrier for improving the anticancer effect of MET. ZNs were fabricated through ethanol injection followed by probe sonication method. The optimum ZN formulation (ZN8) was spherical and contained 5 mg zein and 30 mg sodium deoxycholate with a small particle size and high entrapment efficiency percentage and zeta potential. A stability study showed that ZN8 was stable for up to three months. In vitro release profiles proved the sustained effect of ZN8 compared to the MET solution. Treatment of SEC-bearing mice with ZN8 produced a more pronounced anticancer effect which was mediated by upregulation of P53 and miRNA-543 as well as downregulation of NF-κB and miRNA-191-5p gene expression. Furthermore, ZN8 produced a marked elevation in pAMPK and caspase-3 levels as well as a significant decrease in cyclin D1, COX-2, and PGE2 levels. The acquired findings verified the potency of MET-loaded ZNs as a treatment approach for BC.

Design of quetiapine fumarate loaded polyethylene glycol decorated graphene oxide nanosheets: Invitro-exvivo characterization

Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.

Formulation and Antimicrobial studies of Microencapsulated Musanga cecropioides Stem Bark Extract

Microencapsulation is the process of coating small droplets of liquid or solid materials with a continuous film of polymeric substances. The aim of the research was to formulate microparticles of Musanga cecropioides stem bark extract. The dried, powdered stem bark of Musanga cecropioides was extracted by maceration. The aqueous extract was microencapsulated using polymers such as alginate, pectin and hydroxylpropyl methylcellulose acetate succinate (HPMCAS) by counter-ion coacervation method using an electrostatic droplet generator. The formulated microcapsules were evaluated for flow properties, particle size, drug content, antimicrobial activity and in vitro release kinetics in simulated gastric and intestinal fluids. The microparticles were subjected to stability tests under different temperature (45°C, 25°C and 8°C) and relative humidity (100% RH, 78% RH and 0% RH) conditions for a period of three (3) months. The mean particle size of the microcapsules decreased with increasing applied voltage of the electrostatic generator. Particle size range for the batches of formulated microparticles was 68.20-223.84µm. The percentage entrapment efficiency of the batches of microparticles ranged from 80.26-86.58%. The microparticles lost a significant percent of its drug content after storage at different temperature and relative humidity conditions. The formulated microparticles and crude extract possess significant antibacterial action against both gram positive and negative bacteria as well as antifungal effect against C. albicans. Microparticles of M. cecropioides extract were formulated by counter-ion coacervation method using an electrostatic droplet generator which conferred advantages of sustained drug release, reduced frequency of dosing, masked unpalatable taste, improved stability and enhanced patient acceptance on the crude extract.

Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity

Abstract Purpose Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid. Methods RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size. Results Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (−16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug’s characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid’s ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 μM for free RES to 0.5 ± 0.033 μM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 μMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 μM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension. Conclusion Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.

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.

STUDY ON FORMULATION OF BACTERIAL CELLULOSE NANOFIBERS-COATED NANOLIPOSOMES CONTAINING PACLITAXEL FOR ORAL ADMINISTRATION

Objective: The low oral bioavailability of paclitaxel (PAC) because of its limited aqueous solubility and poor intestinal permeability after being administered orally suggests the need for a sustained release system. The aim of this study is to produce and evaluate in vitro a nanoliposome system that carries paclitaxel (BCN-LIP-PAC) for oral administration. Methods: Thin-film evaporation and electrostatic deposition methods were used to obtain LIP-PAC and BCN-LIP-PAC. Particle size, polydispersity index (PDI), zeta potential, morphological analysis, entrapment efficiency percentage (EE%), and in vitro dissolution studies were used to characterize the developed systems. Results: The nano-range sizes of LIP-PAC and BCN-LIP-PAC (0.1 % BCN) were 112±4.2 nm and 154±6.4 nm, respectively, where EE % were 80.6±2.3 % and 84.6±1.7 %, respectively. BCN-LIP-PAC exhibited good stability in simulated gastrointestinal fluids. The drug release experiments conducted in vitro showed that BCN-LIP-PAC had obvious sustained release behaviors when compared to LIP-PAC. Furthermore, the release rate of PAC from all LIP-PAC and BCN-LIP-PAC was higher in SIF than in SGF. Conclusion: The preparation, characterization, and evaluation of BCN-LIP-PAC (0.1 % BCN) for oral PAC delivery were all successful. In conclusion, the approach presented herein is a promising option for delivering oral sustained-release PAC.

FORMULATION, ANALYSIS AND VALIDATION OF NANOSUSPENSIONS-LOADED VORICONAZOLE TO ENHANCE SOLUBILITY

Objective: This study aimed to enhance the solubility of voriconazole (VRZ) via loading to nanosuspensions using solvent/anti-solvent technique. The optimisation of independent variables (polymer concentrations) was carried out to achieve the desired particle size and maximise the percentage of entrapment efficiency (EE %) and drug loading (DL %) using design-expert®software. Methods: Design-Expert® software, version 13, was used to design and optimise nanosuspensions-loaded VRZ using 23 factorial designs. Concentrations of polyvinylpyrrolidone, hydroxypropyl methylcellulose and poloxamers were selected as independent variables to achieve ideal particle size, polydispersity index (PDI), entrapment efficacy (EE %) and drug loading (DL %). Atomic force microscopy (AFM), differential scanning calorimetry (DSC) and saturated solubility were used to assess the lyophilized nanoparticles. The compatibility between the drug and the polymers was studied using Fourier transform infrared spectroscopy (FTIR). Results: The particle size, PDI, EE %, and DL % were in the range of 15.6–145.6 nm, 0.010-0.120, 55.9 %-91.9 %, and 6.68-36.76 %, respectively. The saturated solubility of nanosuspensions-loaded VRZ (NS-VRZ) relative to free VRZ was increased tenfold in DW and twelvefold in PBS (pH 7.4). DSC thermogram confirmed the incorporation of VRZ in the nanosuspensions. The AFM of NS-VRZ validated spherical tiny particle size with a smooth surface. There is no chemical interaction between VRZ and the polymers, according to an FTIR investigation. Conclusion: The solubility of VRZ was successfully enhanced by loading to nanosuspensions. The solvent/anti-solvent technique was proven to be cost-effective, easy to operate and suitable for the preparation of NS-VRZ using Design-Expert®software.

PREPARATION, CHARACTERIZATION AND EVALUATION OF GELLAN GUM/GLYCOL CHITOSAN BASED BAICALEIN HYDROGEL FOR WOUND HEALING

Objective: The present work was emphasized on preparation, characterization and evaluation of baicalein loaded hydrogel to promote healing of wounds. Methods: Baicalein loaded hydrogel was developed using Gellan gum and Glycol chitosan polymers. Prepared hydrogels were characterized for various parameters like Field Emission Scanning Electron Microscopy (FE-SEM), swelling property, entrapment efficiency, rheology and drug release. Wound healing study was investigated by using incision dead space wound models. Healing effect was assessed by measurement of tensile strength, collagen content, hydroxyproline content, protein content and antioxidant status. Results: The percent entrapment efficiency of optimized hydrogel found to be 89.78±2.07 which resulted in controlled release of drug 85.03% in 12 h. The significant increased level of catalase and superoxide dismutase (SOD) was noticed in dead space wound model. The tensile strength study shows increase in collagen synthesis due to treatment with Baicalein loaded hydrogel. The higher collagen content, better granulation, increase in tensile strength was noticed. Histopathological examination also confirmed higher degree of re-epithelialization and enhanced cutaneous wound repair. Conclusion: In conclusion, biodegradable Baicalein loaded hydrogel might have high potential for wound healing with improved oxidative status and extended release of Baicalein.

Quality-by-Design Based Development of Doxycycline Hyclate-Loaded Polymeric Microspheres for Prolonged Drug Release.

This study explores a novel approach to address the challenges of delivering highly water-soluble drug molecules by employing hydrophobic ion-pairing (HIP) complexes within poly (lactic-co-glycolic acid) (PLGA) microspheres. The HIP complex, formed between doxycycline hyclate (DH) and docusate sodium (DS), renders the drug hydrophobic. The development of the microspheres was done using the QbD approach, namely, Box-Behnken Design (BBD). A comprehensive characterization of the HIP complex confirmed the successful conversion of DH. DH and the HIP complex were effectively loaded into PLGA microspheres using the oil-in-water (O/W) emulsion solvent evaporation method. Results demonstrated significant improvements in percentage entrapment efficiency (% EE) and drug loading (% DL) for DH within the HIP complex-loaded PLGA microspheres compared to DH-loaded microspheres alone. Additionally, the initial burst release of DH reduced to 3% within the initial 15min, followed by sustained drug release over 8days. The modified HIP complex strategy offers a promising platform for improving the delivery of highly water-soluble small molecules. It provides high % EE, % DL, minimal initial burst release, and sustained release, thus having the potential to enhance patient compliance and drug delivery efficiency.

Quality by Design and Characterization of Nimodipine Novel Carriers for the Treatment of Hypertension: Assessment of the Pharmacokinetic Profile

Background: Nimodipine is a highly lipophilic anti-hypertensive drug having 13% oral bioavailability (log P 3.41). Nimodipine is a prominent calcium channel blocker that must be given intravenously for an extended period of time (1-2 weeks) in order to treat cerebral vasospasm. It might be possible to substitute a sustained-release biodegradable formulation for the ongoing intravenous infusion used in this traditional therapy. Objectives: The primary goal of this study was to formulate and evaluate the potentiality of ethosomes to deliver nimodipine, a potent water-insoluble anti-hypertensive drug, through the deeper layers of the skin. The greatest challenge for drug formulation is its poor oral bioavailability and solubility. Methods: Nimodipine-loaded ethosomal gel was developed for transdermal drug delivery to increase solubility and skin penetration and to promote oral bioavailability. Central composite design employing a thin-film hydration method was used to prepare and optimize ethosomes. A better dispersion medium for nimodipine's preparation in ethosomes was selected based on the effect. The design consisted of independent variables as lipid (X1), ethanol (X2), and sonication time (X3). Concentrations were manipulated to examine the effects on three responses, namely the %entrapment efficiency (Y1), vesicle size (Y2), and %cumulative drug release (Y3). Surface morphology and other in vitro tests were used to identify ethosomes containing nimodipine. The preparation of ethosomal gel formulations began with incorporating a single ethosomal formulation (F4) into various concentrations of gelling agents. These studies performed physicochemical characterization, compatibility testing, and in vitro drug release tests on ethosomal gels. In vivo studies involving hypertensive rats were conducted after skin permeation, and ex vivo studies were performed. In order to assess the drug's permeability and deposition, we employed the abdomen skin of rats. Results: The optimal process parameters resulted in ethosomes with 89.9 ± 0.19 percent entrapment efficiency, a vesicle size of 102.37 ± 5.84 nm, and a cumulative drug release of 98.3 ± 0.13%. pH and drug content measurements were consistent with the homogeneous ethosomal gels. Viscosity was found to increase with the spreadability. The ethosomal gel formulation (G2) met the regulatory standards regarding appearance, spreadability, viscosity, and in vitro release studies. Compared to pure nimodipine, ethosomal suspension (F4) and ethosomal gel (G2) formulations had higher ex vivo permeation, steady-state flux, and drug retention. Rats' mean arterial pressure (146.11 ± 0.84 mmHg) was significantly lower (p &lt; 0.01) after after two hours of the experiment than it had been (p &lt; 0.001) (98.88 ± 0.63 mmHg) after six hours. Conclusion: To summarize, ethosomal gels have been found to be lipid carriers that enhance skin permeation and extend the anti-hypertensive effect of nimodipine. Compared to plain gel, ex vivo drug permeation through rat abdominal skin in ethosomal gel was enhanced. Gel-based ethosomal transdermal drug delivery formulations of nimodipine can be used to achieve a faster rate and extend the duration of drug delivery by more than 24 hours.

Anti-Toxoplasma gondii activity of rose hip oil-solid lipid nanoparticles.

Toxoplasma gondii is a highly prevalent pathogen, reported from almost all geographical regions of the world. Current anti-T. gondii drugs are not effective enough in immunocompromised patients, encephalitis, chorioretinitis, and congenital toxoplasmosis. Therefore, the prescription of these drugs has been limited. Rose hip oil (RhO) is a natural plant compound, which shows antibacterial, anticancer, and anti-inflammatory activities. In the current study, the anti-T. gondii and cell toxicity effects of solid lipid nanoparticles (SLNs) loaded by RhO (RhO-SLNs) were evaluated. Emulsification sonicated-homogenization method was used to prepare SLNs. RhO-SLNs were characterized, and their anti-T. gondii and cell toxicity effects were evaluated using invitro analyses. The particle size and the zeta potential of the nanoparticles were 152.09 nm and -15.3 mV nm, respectively. The entrapment efficiency percentage was 79.1%. In the present study, the inhibitory concentration (IC)50 against T. gondii was >1 μg/mL (p-value <.0001). The cell toxicity assay showed cytotoxicity concentration (CC)50 >10 mg/mL (p-value = .017). In addition, at least 75% of T. gondii-infected Vero cells remained alive at concentrations >10 mg/mL. The concentration of 1 mg/mL showed highest anti-Toxoplasma activity and lowest cell toxicity against the Vero cell. Our findings suggest that carrying natural plant compounds with SLNs could be considered an effective option for treatment strategies against T. gondii infections.

Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Development of Transethosomes Delivery System Loaded with Bouea macrophylla Griffith Seed Kernel Extract for Cosmeceutical Application

This research aimed to develop and optimize transethosomes loaded with Bouea macrophylla Griffith seed kernel extract (B-SE). Firstly, extraction procedures using solvent fractionation with various polarity: hexane, ethyl acetate and 95% (v/v) ethanol. The physicochemical properties of B-SE were investigated in terms of partition coefficient (LogP), solubility and pH-stability. To optimize the transethosomes formulation, the compositions were varied in sorts of percent cosurfactant, types of cosurfactant, extract concentration, percent total surfactant and types of particle ingredients (phospholipid or cholesterol). The significant factors influencing physical characteristics of the transethosomes were statistically identified using the 25-1 fractional factorial design. Particle size, polydispersity index (PDI), percent entrapment efficiency (%EE) and ultrastructural morphology of the optimized formulation was then characterized. As a marker of B-SE, ellagic acid (EA) was identified by HPLC at a retention time of 32.506 ± 0.16 min. The LogP of B-SE was 0.17. B-SE was practically insoluble in water but freely soluble in propylene glycol and ethanol. The pH condition that stabilized the extract was pH-5. The optimized formulation, consisted of phospholipid, propylene glycol, TWEEN 20, SPAN 80 and 2.5 mg/ml of B-SE presenting particle sizes of 79.72 ± 2.42 nm, PDI of 0.26±0.02 and %EE of 83.10±0.03% along with a spherical particle shape. To conclude, the optimized transethosomes loaded with B-SE fabricated by phospholipid and propylene glycol has desirable attributes for further developing into an anti-acne cosmeceutical. Nonetheless, the bioactivities and safety profile of the transethosomes were necessary for further investigation. Keywords: Bouea macrophylla Griffith, Transethosomes, Ellagic acid, Fractional factorial design, Nanocarrier

Formulation and Evaluation of Glipizide-loaded Mucoadhesive Microparticle Using Salvia hispanica Seeds Mucilage as Co-polymer

Aims: Chia seed (Salvia hispanica L.) gum is a mucoadhesive, biodegradable polymer with sustained release properties. Objective: The objective of this study was to compare different formulations of glipizide-loaded microparticles using chia seed mucilage and sodium alginate, focusing on sustained release and mucoadhesive properties. Background: The present study aimed to comparatively evaluate various eco-friendly formulations of glipizide-loaded microparticles prepared using chia seed mucilage and sodium alginate. Materials and Methods: Gum was extracted from chia seeds and lyophilized, and preformulation studies were performed according to established protocols. Microparticles were formulated using the ionic gelation method, with sodium alginate as a copolymer and zinc chloride as a cross-linking agent. The prepared microparticles were evaluated using scanning electron microscopy (SEM) for size and particle aggregation, and Fourier Transform infrared spectroscopy (FTIR) for drug-polymer interaction, entrapment efficiency, swelling index, and in vitro drug release. Results: The % yield of chia seed mucilage was 27.35%. The pH of the mucilaginous suspension was 4.67 ± 0.50. The moisture content value was 14.56 % ± 0.50. The values of Carr's index and Hausner's ratio were 22.58 ± 1.89 and 1.38 ± 0.05, respectively. FTIR spectra showed no interaction between pure glipizide and chia seed mucilage, confirming no possible change in glipizide's pharmacology. SEM studies have confirmed the shape of the microparticles to be spherical, with average sizes ranging from 1235.18 ± 8.7 to 1423.25 ± 9.5 µm, and the drug entrapment efficiency ranged from 64.25 ± 2.52 to 81.82 ± 7.56%. The release of glipizide from the microparticles was sustained, and the Higuchi and Korsmeyer-Peppas models were found to be the best-fit kinetic models. Conclusion: The promising copolymer blend of chia seed mucilage and sodium alginate was used for the development of sustained-release dosage forms. A copolymer blend with a ratio of 1:1 produced glipizide-loaded microparticles with sustained release profiles and good mucoadhesive ability, along with a high percentage of drug entrapment efficiency.