Optimized Nanoparticle Formulation Research Articles

Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom.

Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.). Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects. In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay. The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells. It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.

Design Development and Characterization of Nicardipine Solid Lipid Nano-Particulars

The present work was designed and characterized nicardipine solid lipid nano-particulars and formulated into capsule. The formulation was evaluated and stability also as per the specified limits. The nanoparticles were prepared by solid hydrophilic adsorbents. The obtained ratio of 1:1:1:2 of drugs, soy PC, DMPC, and labrasol shows the highest dissolved in water. The liquid form was converted into a solid product using an adsorbent like anhydrous lactose and aerosil 200. The above results indicated aerosil 200 containing which helped in enhanced dissolve state in water. The results indicated the formulation trial-6 %drug content -100.2, entrapment efficiency 84.13 ± 1.64, zeta potential measurement 0.789 ± 0.32, Drug release rate at 3rd hour 81.6% and relative bioavailability of optimized nanoparticle formulation (CNF-6) was significantly increased. As a result, the produced lipid-based formulation shown potential as a method for improving the transfer of lipophilic chemicals that are weakly water-soluble to the aqueous phase, hence improving oral bioavailability

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

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

DEVELOPMENT AND OPTIMIZATION OF POLYMERIC NANOPARTICLES OF GLYCYRRHIZIN: PHYSICOCHEMICAL CHARACTERIZATION AND ANTIOXIDANT ACTIVITY

Objective: The aim of the present study to develop, optimize and characterize Poly (D, L-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) loaded with isolated Glycyrrhizin (Glyc) and investigate for antioxidant activity. Methods: PLGA nanoparticles loaded with Glycyrrhizin were synthesized by an adapted emulsion-evaporation method. Nanoparticles were evaluated for particle size, entrapment efficiency and Polydispersiblity index (PDI). Further, Box Benkhen design was applied for optimization of the formulation parameters and the effect of three independent variables such as PLGA concentration, amount of glycyrrhizin, polyvinyl alcohol (PVA) concentration on particle size, polydispersiblity index and the entrapment efficiency (response variables) were investigated. The antioxidant capacity of optimized nanoparticle formulation loaded with glycyrrhizin was compared with free glycyrrhizin by DPPH assay. Results: The particle size, entrapment efficiency and PDI of optimized Glyc-NPs was found to be 144.20 nm, 68.0% and 0.315 respectively. Optimized Glyc-NPs showed sustained release of drug 79.06% in 48 hours with improved free radical scavenging activity than isolated Glycyrrhizin. Conclusion: PLGA nanoparticles were found to be suitable carrier for Glycyrrhizin at lower levels than originally required for enhanced functional properties.

Optimization of lipid assisted polymeric nanoparticles for siRNA delivery and cancer immunotherapy.

To date, five siRNA-based medications have received clinical approval and have demonstrated remarkable therapeutic efficacy in treating various diseases. However, their application has been predominantly limited to liver-specific diseases due to constraints in siRNA delivery capabilities. In this study, we have developed a siRNA delivery system utilizing clinically approved mPEG-b-PLGA, a cationic lipid, and an ionizable lipid. We optimized this system by carefully adjusting their mass ratios, resulting in highly efficient gene silencing. Furthermore, the optimized nanoparticle formulation, which encapsulates siRNA targeting CD47, induces a robust immune response. This response effectively suppresses the progression of melanoma tumors by blocking this critical immune checkpoint.

FORMULATION AND CHARACTERIZATION OF 50% ETHANOL EXTRACT OF ARECA NUT (Areca catechu) NANOPARTICLES USING THE IONIC GELATION METHOD

The extract of areca nuts (Areca catechu) contains secondary metabolites, such as flavonoids, alkaloids, saponins, tannins, and steroids. These compounds possess pharmacological effects and can be developed into herbal medicine products. The objective of this study is to determine the optimal nanoparticle formulation by varying the concentrations of chitosan and sodium tripolyphosphate. The 50% ethanol extract of areca nuts was obtained through the maceration method. The extract obtained calculation the yield value. Then tested for phytochemical screening. Subsequently, the extract was formulated into nanoparticle colloids with different ratios of extract concentration: chitosan: sodium tripolyphosphate: Tween 80. The resulting nanoparticles were characterized by their particle size, zeta potential, and polydispersity index. The research findings demonstrated that Formula 3 exhibited the best results, with a particle size of 254.2 ± 0,00, zeta potential of 12.7 ± 0,71, and polydispersity index of 0.436 ± 0,03. Keywords: Formulation, Nanoparticles, 50% Ethanol, Areca Nuts, Ionic Gelation.

SILK FIBROIN-BASED ANASTROZOLE NANOPARTICLE LOADED IN SITU INJECTABLE: DEVELOPMENT AND CHARACTERIZATION

Objective: The study aims to find a suitable method of developing silk fibroin-based anastrozole nanoparticles and formulate in situ injectables by loading the optimized nanoparticle formulation for the sustained release treatment of breast cancer. Methods: The nanoparticles were formulated utilizing two different methods, solvent change and precipitation approach using silk fibroin. Prepared nanoparticles characterized in terms of size, zeta potential, polydispersity, and entrapment efficiency. The chosen optimized formulation (SF-ANS-NPs-1) was subsequently analyzed for compatibility investigations by Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, surface morphology, x-ray diffraction, transmission electron spectroscopy, cumulative drug release, and stability studies as per ICH guidelines. Followed by formulating and evaluating in situ injectable gel using pluronic F-127. Results: A particle size of 181.70±1.3 nm was reported by the optimized SF-ANS-NPs-1 formulation. FT-IR and thermal studies confirmed the compatibility of the drug with the polymers, and x-ray diffraction studies indicated crystalline nature. Surface morphology analysis indicated nano-size particle formation. A cumulative drug release (%CDR) of 94.15% was noted at the 168th hour. The results of the stability studies were indicated to be consistent over 90 d. In situ gel formulation showed desired spreadability, sol-gel transition temperature (37±0.5 ℃), viscosity (9.37±1.2 mPa·s), desired acidic pH, and a sustained release for 21 d (98.11%) with three months accelerated stability. Conclusion: The results suggested that the combination of anastrozole with silk fibroin in the form of nanoparticles and in situ gelling systems could be an undoubtedly effective delivery method for prolonging breast cancer therapy.

Development of Lipid Nanoparticles Containing Omega-3-Rich Extract of Microalga Nannochlorpsis gaditana.

Microalgae are described as a new source of a wide range of bioactive compounds with health-promoting properties, such as omega-3 lipids. This biomass product is gaining attention mainly due to its potential to accumulate different compounds depending on the species and environment, and it has been commonly recognized as a valuable nutraceutical alternative to fish and krill oils. In this work, we obtained the extract of the microalga Nannochloropsis gaditana, selected on the basis of its content of eicosapentaenoic acid (EPA) and glycolipids, which were determined using GC-MS and high-performance liquid chromatography (HPLC), respectively. To develop an oral formulation for the delivery of the extract, we used a 23 factorial design approach to obtain an optimal lipid nanoparticle formulation. The surfactant and solid lipid content were set as the independent variables, while the particle size, polydispersity index, and zeta potential were taken as the dependent variables of the design. To ensure the potential use of the optimum LN formulation to protect and modify the release of the loaded microalga extract, rheological and differential scanning calorimetry analyses were carried out. The developed formulations were found to be stable over 30 days, with an encapsulation efficiency over 60%.

Design and in vitro/in vivo Evaluation of Polyelectrolyte Complex Nanoparticles Filled in Enteric-Coated Capsules for Oral Delivery of Insulin

Insulin is one of the most important drugs in the treatment of diabetes. There is an increasing interest in the oral administration of insulin as it mimics the physiological pathway and potentially reduces the side effects associated with subcutaneous injection. Therefore, insulin-loaded polyelectrolyte complex (PEC) nanoparticles were prepared by the ionic cross-linking method using protamine sulfate as the polycationic and sodium alginate as the anionic polymer. Taguchi experimental design was used for the optimization of nanoparticles by varying the concentration of sodium alginate, the mass ratio of sodium alginate to protamine, and the amount of insulin. The optimized nanoparticle formulation was used for further in vitro characterization. Then, insulin-loaded PEC nanoparticles were placed in hard gelatin capsules and the capsules were enteric-coated by Eudragit L100-55 (PEC-eCAPs). Hypoglycemic effects PEC-eCAPs were determined in vivo by oral administration to diabetic rats. Furthermore, in vivo distribution of PEC nanoparticles was evaluated by fluorescein isothiocyanate (FITC) labelled nanoparticles. The experimental design led to nanoparticles with a size of 194.4 nm and a polydispersity index (PDI) of 0.31. The encapsulation efficiency (EE) was calculated as 95.96%. In vivo studies showed that PEC-eCAPs significantly reduced the blood glucose level of rats at the 8th hour compared to oral insulin solution. It was concluded that PEC nanoparticles loaded into enteric-coated hard gelatin capsules provide a promising delivery system for the oral administration of insulin.

DEVELOPMENT OF NANO BASED FILM FORMING GEL FOR PROLONGED DERMAL DELIVERY OF LULICONAZOLE

Objective: Luliconazole (LZL) has low aqueous solubility that limits its dermal bioavailability and acts as a barrier to topical delivery. The conventional topical formulations have a limited ability to retain the drug over the skin for a prolonged period. The main objective of the study was to formulate and characterize LZL loaded ethyl cellulose (EC) nanoparticles and formulate them as a film-forming gel (FFG) for prolonged delivery in fungal skin infections.Methods: The solvent evaporation technique was used for the preparation of nanoparticles of LZL by using EC as a polymer. The prepared nanoparticles were evaluated for physical appearance, production yield, entrapment efficiency, drug content, particle size, zeta potential, Polydispersity index (PDI), and in vitro drug release. Then the nanoparticles were incorporated into FFG formulation by using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as the gelling agent. The prepared FFG was evaluated for pH, Viscosity, Spreadability, in vitro drug release studies, in vitro antifungal studies, and release kinetic studies.Results: The optimized nanoparticle formulation F5 having drug to polymer ratio of 1:2 showed satisfactory production yield (86.32%), entrapment efficiency (83.36%), drug content (42.86), particle size (125.3), and 93.72% of in vitro drug release after 24 h (h). The optimized FFG formulation FFG4 showed the shortest film-forming time of 5.06 min (min), percentage Cumulative drug release of 92.18% after 24 h, and had promising in vitro antifungal activity.Conclusion: The prepared FFG could be used with promising potential for fungal infection of the skin.

DEVELOPMENT OF NANOPARTICLES SUSPENSION FOR PAEDIATRIC DRUG ADMINISTRATION

Objective: Enalapril maleate (EM) is an angiotensin-converting enzyme (ACE) inhibitor. It is generally prescribed for the treatment of hypertension, heart failure and chronic kidney diseases in adults and children. EM 2.5 mg, 5 mg, 10 mg and 20 mg tablets and EM injection 1.25 mg/ml are currently available in the market. But a liquid paediatric formulation of this medicine is not currently available. Also, it is a BCS class III drug, having a bioavailability of approximately 60%. The present study proposes a new strategy for improvement of drug bioavailability and taste masking: EM nanoencapsulation within polymeric nanoparticles suspensions prepared with Eudragit RS100 (ERS100) as polymer and Tween 80 as a stabilizer, aiming at obtaining a liquid dosage form suitable for paediatric administration.Methods: Nanoprecipitation method used for the preparation of nanoparticles suspension. The preparations were evaluated for drug content, entrapment efficiency, particle size, zeta potential, polydispersity index, pH, viscosity and in vitro drug release. Based on the entrapment efficiency, viscosity and in vitro drug release the optimized formulation was selected. Optimized formulation evaluated for taste, ex vivo intestinal permeation, differential scanning calorimetry, scanning electron microscopy and release kinetic studies.Results: The optimized nanoparticle formulation F8 having drug to polymer ratio of 1:100 showed satisfactory drug content (95.1%), entrapment efficiency (77.71%), particle size (198.47 nm), pH (6.36), viscosity (2.9 x〖10〗^(-3)Pa•s) and 81.2% drug release after 12 h. The formulation has taste-masking properties and shows 84.6% drug permeation through the goat intestine within 12 h.Conclusion: The prepared nanoparticles suspension of Enalapril maleate was found to be an effective liquid pharmaceutical dosage form for paediatric administration with taste-masking properties.

Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid-Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration.

The methacrylic acid–ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/− 9.14 nm with a PDI of 0.37085 +/− 0.014 and a zeta potential of −13.7125 +/− 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.

QbD-based Formulation Optimization and Characterization of Polymeric Nanoparticles of Cinacalcet Hydrochloride with Improved Biopharmaceutical Attributes

The aim of the present work was to prepare QbD enabled optimization, and to improve the oral bioavailability of freeze-dried polymeric nanoparticles of cinacalcet hydrochloride manufactured by nanoprecipitation and ultrasonication methods using polymers PLGA, and poloxamer-188. The initial screening and optimization were carried out for the formulations by employing Taguchi and Box-Behnken Designs. The FT-IR and DSC revealed no interactions and had no incompatibility among the selected drug and polymers. The nanoparticles were characterized for % drug release, particle size analysis, zeta potential, PDI, SEM, TEM, P-XRD, TGA, DTA, in vitro, and in vivo drug release study. In vitro drug release study showed sustained release of the drug from the optimized batch by diffusion mechanism. The optimized nanoparticle formulation was recognized by numerical and graphical methods using validation of the experimental model. The optimized batch was stable as per the ICH stability guidelines for 6 months with no considerable alternation noticed in particle size, entrapment efficiency, and in vitro drug release. The pharmacokinetic parameters of AUC and Cmax data for the optimized formulation increased 3- and 2.9-folds compared to the pure-drug suspension. The prepared polymeric nanoparticles formulation is an alternative delivery system for enhanced therapeutic efficacy and bioavailability potential of a model drug to manage long-term normocalcemia in patients with preliminary hyperparathyroidism.

Rufinamide-Loaded Chitosan Nanoparticles in Xyloglucan-Based Thermoresponsive In Situ Gel for Direct Nose to Brain Delivery.

In 2004, the US FDA approved Rufinamide, an anti-epileptic drug under the brand name Banzel®. In 2015, Banzel® received approval for its use in pediatric patients (ages 1–4 years). Rufinamide shows low oral bioavailability due to a low dissolution rate resulting in less of the drug reaching the brain. This has led to the high dose and dosing frequency of Rufinamide. In this work, using the principle of design of experiments (DoE), we have formulated Rufinamide-loaded chitosan nanoparticles and suspended them in a solution of a thermoresponsive polymer–tamarind seed xyloglucan to form a nasal in situ gel for direct nose to brain delivery of Rufinamide. The nanoparticles were characterized for particle size, entrapment efficiency, zeta potential, and physical stability. The in situ gel formulations were characterized for rheological properties, stability, and in vivo plasma and brain pharmacokinetics. Pharmacokinetic parameters were computed for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles and compared with the pharmacokinetic parameters of an aqueous suspension of plain Rufinamide. The percentage of direct transport efficiency (% DTE) and direct transport percentage (%DTP) values were calculated for all the formulations. The optimized nanoparticle formulation showed a size of 180 ± 1.5 nm, a zeta potential of 38.3 ± 1.5 mV, entrapment efficiency of 75 ± 2.0%, and drug loading of 11 ± 0.3%. The in situ gelling formulation of nanoparticles showed a solution to the gel transition temperature of 32°C. The %DTE values for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles were 988.5 and 1177.3 and the %DTP values were 86.06 and 91.5 respectively.

Development and evaluation of polycaprolactone based docetaxel nanoparticle formulation for targeted breast cancer therapy

The present study describes the preparation, characterization, and applications of newly developed polymeric poly-ɛ-caprolactone (PCL)/pluronic F108 nanoparticles, loaded with anticancer drug, and near infrared (NIR) dye for assessing the localization in the breast cancer model system. Docetaxel and NIR dye, “1,1′-dioctadecyl- 3,3,3′,3′- tetramethylindotricarbocyanine iodide (DiR)” loaded, poly-ɛ-caprolactone (PCL)/pluronic F108–based nanoparticles were formulated by nanoprecipitation method. This formulation was then characterized using various physicochemical methods including size distribution, zeta potential, surface morphology, drug entrapment efficiency, loading capacity, differential scanning calorimetry, in vitro release, and kinetics are performed. In vitro cell proliferative studies of human breast cancer BT-474 cells were carried out to evaluate the anticancer efficacy of the nanoparticles. The role of pluronic F108 was also evaluated in cell uptake of the nanoparticles. Drug- and NIR dye–loaded nanoparticles localization at tumor site were studied using noninvasive infrared dye imaging. The optimized nanoparticle formulation had a particle size of 100–300 nm, poly dispersity index of 0.156 and zeta potential of − 7.37 mV ± 4.93 mV. Drug release from the nanoparticle system followed Higuchi kinetics, suggesting diffusion mediated drug release. DSC studies suggest that the drug is either in amorphous or disordered crystalline state in the nanoparticle formulation. The increased accumulation of the PCL/ F108 nanoparticles in vivo suggests its potential as a superior targeted drug delivery system.

Extended levobunolol release from Eudragit nanoparticle-laden contact lenses for glaucoma therapy

BackgroundMajorly, the reason for the permanent loss of vision is glaucoma. But the currently available common treatment methodologies such as eye drops have various disadvantages like patient incompliance due to repeated administration and poor (1–5%) bioavailability leading to poor efficiency. The objective of this research was to formulate Eudragit-based nanoparticles of levobunolol incorporated into a contact lens to obtain sustained ocular delivery of levobunolol at the therapeutics level. Eudragit nanoparticles of levobunolol were formulated by nanoprecipitation methodology utilizing different ratios of Eudragit S100 and polyvinyl alcohol. The prepared nanoparticles were evaluated and optimized by efficiency of entrapment, particle size, morphology of surface and zeta potential. The optimized nanoparticles were then entrapped into the matrix of the contact lens by the soaking method which were then characterized and compared for optical clarity study, equilibrium swelling study, shelf life and in vitro drug release in simulated tear fluid followed by ex vivo transcorneal permeation study.ResultsFormulation F3 was obtained as optimized nanoparticle formulation with 102.61 nm ± 3.92 of particle size, − 22.2 mV ± 2.76 of zeta potential and 86.995% ± 1.902 of efficiency of entrapment. The equilibrium swelling index and transmittance of nanoparticle incorporated into contact lenses showed better results when compared to drug solution-loaded lenses. In vitro release indicated more sustained drug profiles (84.33% ± 0.34 of drug release over a period of 12 days) as compared to drug solution-loaded lenses (89.282% ± 0.900 of drug release over a period of 3 days). Ex vivo transcorneal permeation studies showed more permeation (6.75% ± 0.170) through contact lenses as compared to marketed eye drops (3.03% ± 0.088).ConclusionThis research demonstrates the remarkable results of drug-laden contact lenses to serve as a great medium for the continued delivery of ocular drugs without affecting the physical and optical characteristics of the lens content.

Development and Ex-vivo Evaluation of Topiramate Mucoadhesive Nanoparticles for Intranasal Delivery

Topiramate is a second-generation antiepileptic drug used in partial, generalized seizures as an oral tablet. Oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Hence, the present study was aimed to develop topiramate mucoadhesive nanoparticles for intranasal administration using ionotropic gelation method. The developed nanoparticles were evaluated for physico-chemical properties like particle size, zeta potential, surface morphology, drug content, entrapment efficiency, in vitro drug release, mucoadhesive strength, and ex vivo permeation studies in excised porcine nasal mucosa. Optimized nanoparticle formulation (T9) was composed oil mucoadhesive agent (Chitosan 1% w/w), cross linking polymer (TPP) and topiramate 275mg, 100mg and 4% respectively. It showed particle size of 350nm, high encapsulation efficacy and strong mucoadhesive strength. In vitro drug diffusion of optimized formulation showed 95.12% release of drug after 180min. Ex-vivo permeation of drug across nasal mucosa was 88.05 % after 180min. Nasocilial toxicity studies showed optimized formulation did not damage the nasal mucosa. Thus, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.

Promising bioadhesive ofloxacin-loaded polymeric nanoparticles for the treatment of ocular inflammation: formulation and in vivo evaluation.

Our work tackles the combined advantages of both nanotechnology and the bioadhesive gel properties which were utilized to design an ocular drug delivery system that is capable to treat ocular inflammation. Nanoparticles encapsulating an antibiotic drug, ofloxacin, were fabricated using emulsion solvent evaporation technique adopting 23 full factorial design to evaluate the effect of formulation parameters: that is to say, the molecular weight of the polymer (polycaprolactone), amount of Kolliphor P188, and presence of the charge inducer (chitosan hydrochloride) on the measured responses: drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The results show that the optimized LPCL-NP2 formulation (composed of low molecular weight polycaprolactone, 500mg of Kolliphor P188, 0.25% chitosan hydrochloride, and 50mg ofloxacin) displayed a sphere shape with EE%, PS, PDI, and ZP values of 89.73 ± 0.04%, 195.4 ± 13.17nm, 0.323 ± 0.01, and 55.4 ± 0.66mV, respectively. DSC study confirmed the amorphous nature of the drug. The optimized nanoparticle formulation was then further incorporated into the following two ocular formulations: gel (LPCL-NP2-G4) and in situ forming gel (LPCL-NP2-ISG4). The penetration of optimized ocular formulations was assessed by confocal laser scanning microscopy. The antimicrobial study was conducted for the following three ocular formulations: LPCL-NP2 presented as eye drops, LPCL-NP2-G4, and LPCL-NP2-ISG4 as well as the market product using rabbits which were infected in their eyeswith Escherichia coli. Results revealed that rabbits treated with LPCL-NP2-ISG4 demonstrated a remarkable antibacterial efficacy and evident low bacterial growth which was additionally assuredby the histopathological examination of eye biopsies compared with the other investigated groups. Thus, a novel ofloxacin-loaded nanoparticle formulation based on polycaprolactone is presented in the form of mucoadhesive non-irritatingin situ forming ocular gel possessing a superior antibacterial activity. Graphical abstract.

Novel lipid–polymer hybrid nanoparticles incorporated in thermosensitive in situ gel for intranasal delivery of terbutaline sulphate

Aim The present work aimed to improve the bioavailability of terbutaline sulphate (TS) and to prolong its nasal residence time for the treatment of asthma. Methods Chitosan/pectin polyelectrolyte complex nanoparticles (CS/PC) were prepared by ionic gelation method and coated with phospholipid (PL) and then incorporated into optimised thermosensitive in situ gel. Results The optimal PL-coated nanoparticle formulation (LP1) showed the smallest particle size (345.5 nm), the highest zeta potential (32.9 mV) and the greatest percent drug released after 6 h (71%). The optimum in situ gel loaded with LP1 (NG3) showed three times greater permeation through nasal mucosa than aqueous solution of TS and revealed about 94% and 92% of the effect of IV injection of drug solution on tidal volume and peak expiratory flow in histamine treated rats, respectively. Conclusion The developed PL-coated CS/PC/in situ gel could be considered as a promising intranasal formulation of TS for asthma management.

Development and Characterization of Starch/Gelatin Microneedle Arrays Loaded with Lecithin–Gelatin Nanoparticles of Losartan for Transdermal Delivery

The aim of this work was to develop and characterize biodegradable polymeric microneedle arrays loaded with (i) losartan potassium powder and (ii) nanoparticles loaded with losartan potassium dispersed in polymeric matrix (starch/gelatin) as innovative pharmaceutical forms intended to be used for blood pressure control. The lecithin/gelatin nanoparticles were prepared by desolvation method. The independent variables were lecithin/gelatin amount and stirring speed while particle size, PDI (polydispersity index), and entrapment efficiency were the dependent variables studied. The optimized nanoparticle formulation was also characterized in terms of ζ potential and morphology. The mold of microneedle manufacture was created using a 3D printer by molding, and the microneedle arrays were prepared by micromolding method. The independent variables were starch/gelatin amount and drug form while fracture force, bioadhesion, and post-wetting bioadhesion were the dependent variables evaluated. The optimized microneedle array formulations were also characterized and evaluated in terms of morphology, release profiles, and in vitro losartan skin permeation studies. The optimized nanoparticle formulation was of 170.3 ± 3.1 nm of size, with 0.201 ± 0.013 of PDI, 40.45 ± 2.27% of entrapment efficiency, and − 32.9 ± 0.8 mV of ζ potential. The mold had an array of 25 microneedles with a height of 1.5 mm each. The optimized microneedle arrays were successful in terms of fracture force with a value of 408.3 ± 6.1 gf for MP and 320.2 ± 17.4 gf for MN. The results of in vitro skin permeation studies indicated that therapeutic losartan concentrations can be reached by using a microneedle array of 49 cm2 for MP and 13 cm2 for MN. The optimal formulation of the microneedle array with nanoparticles constitutes the most suitable option for skin losartan delivery.