Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery

Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood–brain barrier.

Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route.

Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells.

Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6?±?4.7?nm and zeta potential ?16.3?±?3.7?mV exhibited percentage entrapment efficiency of 27.95?±?4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone.

Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.     

Encapsulation of low lipophilic and slightly water-soluble dihydroartemisinin in PLGA nanoparticles with phospholipid to enhance encapsulation efficiency and in vitro bioactivity

Context: PLGA nanoparticles have been widely utilised to encapsulate lipophilic drugs for sustained release.

Objective: This study was to enhance encapsulation efficiency and drug loading for the poorly lipophilic drug dihydroartemisinin (DHA) in PLGA nanoparticles, where amphiphilic phospholipid was employed as the intermediate. Materials and methods: DHA-phospholipid complex formulation was optimised using the response surface method. DHA-phospholipid complex-nanoparticles (DHA-PLC-NPs) were prepared using the solvent evaporation method. Results: The particle size, zeta potential, entrapment efficiency and drug loading of the nanoparticles were 265.3?±?7.9?nm, ?21.4?±?6.3?mV, 74.2?±?6.5% and 2.80?±?0.35%, respectively. Compared with the rapidly released free form, DHA underwent sustained release from the nanoparticles. DHA-PLC-NPs presented stronger cell proliferative inhibition than DHA treatment alone and apoptosis was obviously induced after DHA-PLC-NPs treatment. Conclusion: Phospholipid complexes are useful intermediate to improve the lipophilicity of drugs, the interaction with the hydrophobic core of PLGA and the encapsulation efficiency of poorly lipophilic drugs in polymeric nanoparticles.     

Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy

Objective: The aim of the present work was to investigate the efficacy of nanostructured lipid carriers (NLCs) to enhance the brain targeting of lamotrigine (LMT) following intranasal (IN) administration.

Methods: Formulation was optimized using four-factor three levels Box– Behnken design to establish the functional relationships between variables on responses, that is, particle size, entrapment efficiency (EE) and percentage cumulative drug release of LMT-loaded NLCs. NLCs were evaluated for particle size, surface morphology, %EE and in vitro release and ex vivo permeation. The developed formulation was subjected to stability study, in vivo efficacy and scintigraphic study in Wistar rat model.

Results: The NLCs had a mean particle size of 151.6 ± 7.6 nm, polydispersity index of 0.249 ± 0.035, zeta potential of 11.75 ± 2.96 mV and EE of 96.64 ± 4.27%. The drug release from NLCs followed Fickian diffusion with a flux value of 11.73 μgcm^?2h^?1. Sustained drug concentration was obtained in NLCs carrying LMT after IN administration after 24 h. γ scintigraphy studies further proved high accumulation of drug in brain.

Conclusion: Hence we can conclude that IN administration of LMT NLCs in rats is able to maintain higher brain concentration of LMT compared to IN and oral drug solution.     

Development,characterization and nasal delivery of rosmarinic acid-loaded solid lipid nanoparticles for the effective management of Huntington’s disease

Abstract

Objective: The objective of the present study was to investigate the potential use of solid lipid nanoparticles (SLNs) as a drug delivery system to enhance the brain-targeting efficiency of rosmarinic acid (RA) following intranasal (i.n.) administration.

Materials and methods: The RA-loaded SLNs was prepared by the hot homogenization technique, in which glycerol monostearate (GMS) as lipid, tween 80 and soya lecithin were used as surfactant along with hydrogenated soya phosphatidyl choline (HSPC) as a stabilizer, and were characterized for particle size, zeta potential (ZP), in vitro study. Nasal delivery of the developed formulation followed by the study of behavioral (locomotor, narrow beam, body weight) and biochemical parameters (glutathione, lipid peroxidation, catalase and nitrite) in wistar rat was carried out.

Results: Optimized RA-loaded SLNs using tween 80 (SLNPRT) have the mean size of (149.2?±?3.2?nm), ZP (?38.27?mV) entrapment efficiency (61.9?±?2.2%). 3-NP-treated rat significantly increased behavioral alterations, oxidative damage as compared with the control group. SLNPRT treatment significantly improved behavioral abnormalities and attenuated the oxidative stress in 3NP-treated rats. However, the nasal delivery of SLNPRT produced significant therapeutic action as compared to intravenous application. In the organ distribution study, brain drug concentration was found to be 5.69?µg, in pharmacokinetic study C_max, t_max, t_1/2, AUC values were found to be 0.284?µg/ml, 1.5?h, 3.17?h, and 1.505?µg/ml/h, respectively.

Conclusion: The encouraging results confirmed the developed optimized RA-loaded SLNs formulation following the non-invasive nose-to-brain drug delivery that is a promising therapeutic approach for the effective management in Huntington disease.     

5-Fluorouracil shell-enriched solid lipid nanoparticles (SLN) for effective skin carcinoma treatment

Context: The effective treatment of skin carcinoma is warranted for targeting the chemotherapeutic agents into tumor cells and avoiding unwanted systemic absorption.

Objective: This work was dedicated to the purpose of engineering highly penetrating shell-enriched nanoparticles that were loaded with a hydrophilic chemotherapeutic agent, 5-fluorouracil (5-FU).

Methods: Varying ratios of lecithin and poloxamer188 were used to produce shell-enriched nanoparticles by enabling the formation of reversed micelles within this region of the SLN. The localization of 5-FU within the shell region of the SLN, was confirmed using 5-FU nanogold particles as a tracer. SLN were introduced within sodium carboxy methylcellulose hydrogel, and then applied onto the skin of mice-bearing Ehrlich’s ascites carcinoma. The mice were treated with the gel twice daily for 6 weeks.

Results: The transmission electron microscope (TEM) revealed the formation of uniform nanoparticles, which captured reversed micelles within their shell region. The SLNs’ had particle size that ranged from 137?±?5.5?nm to 800?±?53.6, zeta potential of ?19.70?±?0.40?mV and entrapment efficiency of 47.92?±?2.34%. The diffusion of the drug-loaded SLN (269.37?±?10.92?μg/cm²) was doubled when compared with the free drug (122?±?3.09?μg/cm²) when both diffused through a hydrophobic membrane. SLN-treated mice exhibited reduced inflammatory reactions, with reduced degrees of keratosis, in addition to reduced symptoms of angiogenesis compared to 5-FU-treated mice.

Conclusion: SLN possesses the capacity to be manipulated to entrap and release hydrophilic antitumor drugs with ease.     

Lipid-core nanocapsules are an alternative to the pulmonary delivery and to increase the stability of statins

Abstract

Aims: Lipid-core nanocapsules (LNCs) loaded with simvastatin (SV, SV-LNC) or lovastatin (LV, LV-LNC) were formulated for pulmonary administration.

Methods: The LNC suspensions were characterized physicochemically, their stability was evaluated, and drug delivery by the pulmonary route was tested in vitro.

Results: The loaded LNCs had a particle size close to 200?nm, a low polydispersity index, and a zeta potential around ?20?mV. The encapsulation efficiency was high for SV (99.21?±?0.7%) but low for LV (20.34?±?1.2%). SV release from nanocapsules was slower than it was from SV in solution, with a monoexponential release profile, and the drug emitted and aerosol output rate was higher for SV-LNCs (1.58?µg/s) than for SV in suspension (0.54?µg/s).

Conclusions: SV-LNCs had a median aerodynamic diameter of 3.51?µm and a highly respirable fraction (61.9%), indicating that nanoparticles are a suitable system for efficient delivery of simvastatin to the lung.     

In vivo brain microdialysis to evaluate FITC-dextran encapsulated immunopegylated nanoparticles

Context: Delivery of drugs and dyes through intact blood–brain barrier (BBB) is extremely sought-after. A safe and reliable measurement of delivery efficacy in live animals is necessary.

Objective: To investigate the brain uptake of FITC-dextran MW 4000 (FD4) by CD71/OX-26 coated nanoparticles by microdialysis sampling and fluorescence/confocal microscopy.

Materials and methods: Methoxy-poly(ethylene glycol)-poly(lactide) (Met-PEG-PLA) and maleimide-poly(ethylene glycol)-poly(lactide) (Mal-PEG-PLA) nanoparticles were prepared by nanoprecipitation. The surfaces of the prepared nanoparticles were embellished with CD-71/OX-26 antibodies for brain targeting. Male Sprague Dawley rats received 0.4?mg/kg FD4 and equivalent nanoparticulate formulation through lateral tail vein. Animals were euthanized 24?h postadministration, after which the tissues were harvested and analyzed for FD4 concentrations. Tissues were fixed with paraformaldehyde, cryotomed to 20 µm sections, and analyzed by Total Internal Reflection microscopy.

Results: Particle sizes of 200?±?25?nm and zeta potentials of ?18?±?1 mV were obtained. FD4 concentrations, determined using in vivo brain microdialysis, were high on the first day (~360?ng/mL) compared to 60?ng/mL on the following 2 days. The nanoparticle treated animals showed significantly higher (p < 0.05) FD4 concentrations in the brain than pure-FD4 treated animals. Immunopegylated nanoparticles sustained and enhanced Central nervous system (CNS) concentration of hydrophilic dye for at least 3 days.

Conclusion: Immunopegylated nanoparticles produce enhanced and sustained uptake of brain permeability marker FD4 relative to controls.     

Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine

Tacrine-loaded chitosan nanoparticles were prepared by spontaneous emulsification. The particle size and zeta potential was determined by scanning probe microscopy and Zetasizer, respectively. The prepared particles showed good drug-loading capacity. The in vitro release studies showed that after the initial burst, all the drug-loaded batches provided a continuous and slow release of the drug. Coating of nanoparticles with Polysorbate 80 slightly reduced the drug release from the nanoparticles. Release kinetics studies showed that the release of drug from nanoparticles was diffusion-controlled, and the mechanism of drug release was Fickian. The biodistribution of these particles after intravenous injection in rats showed that of nanoparticles coated with 1% Polysorbate 80 altered the biodistribution pattern of nanoparticles.From the Clinical EditorIn this paper, chitosan nanoparticles are investigated in a pre-clinical study as an optimized delivery system for tacrin, a drug with potential significance in Alzheimer's disease. The preparation showed optimal pharmacokinetic characteristics in a rat model.     

Combined strategy for suppressing breast carcinoma MCF-7 cell lines by loading simvastatin on alpha lipoic acid nanoparticles

ABSTRACT

Background: Augmentation of simvastatin (SMV) cytotoxicity in breast carcinoma cell lines MCF-7, by: improvement of cellular uptake and loading on alpha lipoic acid (ALA).

Methods: In this study, SMV was loaded on ALA nanoparticles and characterized for surface morphology, SMV entrapment efficiency percent (%EE), zeta potential and release profile. Cellular viability, morphology and uptake and DNA fragmentations were analyzed as a hallmark of cellular apoptosis.

Results: TEM images demonstrated spherical nanoparticles with particle size 104.7 ± 5.5 nm, SMV %EE was 95.8 ± 2.1% with a zeta potential – 23.6 ± 5.4 mV, and release properties were significantly enhanced. IC₅₀ was decreased to 22.2 ± 2.4 µM while raw SMV was 49.3 ± 6.6 µM. Cellular uptake of SMV-ALA nanoparticles was increased by about 3- and 2-folds after 2 and 4 h, respectively. DNA fragments confirmed the apoptosis property of ALA, which is associated with SMV cytotoxicity.

Conclusion: This study suggests evidence that SMV loaded on ALA nanoparticles increases the MCF-7 cellular uptake and cytotoxic effects induced by SMV as revealed by significantly enhanced cell death rates in MCF-7 cells. These findings demonstrate that ALA induces cell death, which makes the combination a candidate for tumor therapy.     

Formulation development of albumin based theragnostic nanoparticles as a potential delivery system for tumor targeting

Background: Generally, chemotherapeutic drugs attack on both normal and tumor cells non-specifically causing life threatening side effects, necessitating targeted drug delivery to tumors.

Purpose: The purpose of this study is to formulate albumin-based nanoparticles for tumor targeted drug delivery and noninvasive diagnosis.

Methods: Albumin based nanoparticles (NPs) were developed as a potential tumor theragnostic agent by entrapping an anti cancer drug, doxorubicin and a near infrared dye, indocyanine green. Theragnostic nanoparticles were prepared using a well established coacervation/nanoprecipitation method followed by lyophilization. The formulation was optimized by varying process parameters using full factorial design of experiments. Release of dye and drug from NPs and physical state of the drug in NPs was studied using DSC. The NPs were injected into tumor bearing mice intravenously and imaged using a bio-imager.

Results: The optimized nanoparticle formulation had a particle size of 125.0?±?1.8?nm, poly dispersity index of 0.180?±?0.057 and zeta potential of ?32.7?±?0.9 mV. The release of dye and drug from the nanoparticles was determined to be quasi-fickian diffusion mediated. Differential scanning calorimetry (DSC) studies revealed the stability of drug in the NP. The in-vivo studies showed enhanced accumulation of the dye loaded NPs at the tumor site than the dye solution, thus allowing noninvasive tumor monitoring.

Conclusion: These results project the newly proposed and evaluated nanoparticle formulation as a potential tumor targeting and imaging delivery system.     

Delivery of Loperamide Across the Blood-Brain Barrier with Polysorbate 80-Coated Polybutylcyanoacrylate Nanoparticles

Purpose. The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier. Methods. Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test. Results. Intravenous injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. Conclusions. Polysorbate 80-coated PBCA nanoparticles loaded with loperamide enabled the transport of loperamide to the brain.     

Improvement of oral efficacy of Irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations

Background: Irinotecan (IRN) (CPT-11) is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein (p-gp) receptors. Hence, no oral formulation is marketed for IRN till date and its oral ingestion continues to remain a challenge.

Aim of study: The study aims to develop a nanoformulation i.e. Chitosan (CS)-coated-IRN-loaded-poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) (CS-IRN-PLGA-NPs)in order to enhance oral bioavailability of IRN.

Results: Developed formulation revealed particle size, 166.9?±?13.63?nm, zeta potential, 14.67?±?1.08?mV and drug content (42.69?±?1.97 µg/mg), with spherical shape and smooth surface. Cytotoxicity studies, performed against human breast adenocarcinoma cell lines (MCF-7), confirmed the superiority of IRN-CS-PLGA-NPs over free IRN solution (IRN-S). Cellular transport conducted on human colon adenocarcinoma cell line (Caco-2) exhibited a higher permeability of 1.33 folds for IRN through CS-IRN-PLGA-NPs as compared to IRN-S (p?Discussion: CS-IRN-PLGA-NPs approach may be effectively utilised, to replace pre-existing intravenous therapy thus providing ‘patient care at home.     

Collagen loaded nano-sized surfactant based dispersion for topical application: formulation development,characterization and safety study

Abstract

Collagen, a high molecular weight, hydrophilic and highly abundant protein is known to have anti-ageing, anti-wrinkle, anti-acne, anti-scar and wound healing properties. High molecular weight and hydrophilic nature hinder its effective topical delivery. So, the objective of present study was to develop effective topical nano-surfactant dispersion (NSD) for collagen delivery. NSD was prepared from sorbitan monostearate (Span60) and cholesterol using ethanol injection method followed by probe sonication. NSD was characterized for entrapment efficiency (%EE), size and size distribution (Z-avg and polydispersity index (PDI)), shape, zeta-potential (ζ), in vitro drug release, skin hydration and skin irritation test and histopathological examination. Optimized NSD (NSD3) had %EE, z-avg, PDI and ζ-potential of 77.56%?±?1.09%, 158.1?±?2.31?nm, 0.211 and ?17.2?±?0.64?mV, respectively. In in vivo skin hydration test, NSD treatment showed nearly 2.5-fold and 3-fold increase in the thickness of stratum corneum (SC) as compared to the collagen gel treated and untreated skin, respectively. The mean scores of skin irritation test in two animal species, rats and rabbits, were found to be 1.42?±?1.01 and 1.71?±?0.29, respectively, indicating the non-irritant nature of collagen loaded NSD. Histopathology of the skin after application of developed NSD showed non-significant changes in skin anatomy indicating its safe nature.     

Intranasal delivery of tapentadol hydrochloride–loaded chitosan nanoparticles: formulation,characterisation and its in vivo evaluation

The aim of the present investigation was to formulate tapentadol hydrochloride–loaded chitosan nanoparticles (CS-NPs) for nose to brain delivery. Chitosan nanoparticles were prepared using ionotropic gelation technique. Optimisation of the formulation and process parameters was done using Box–Behnken Design. The entrapment efficiency, drug loading, Z-average size and zeta potential of the optimised batch were 63.49?±?1.61%, 17.25?±?1.38%w/w, 201.2?±?1.5?nm and +49.3?mV, respectively. In-vitro release study showed 84.04?±?1.53% drug release after 28?h, while ex vivo studies indicated higher permeation of CS-NPs through nasal mucosa. The nanoparticles exhibited good mucoadhesiveness, haemocompatibility and safety as evidenced by histopathology. The results of the pharmacodynamic study revealed prolongation of the analgesic activity. The intranasal instillation of CS-NPs resulted in the higher concentrations in brain compared to the drug solution and intravenous administration of CS-NPs. In a nutshell, intranasal administration of tapentadol hydrochloride–loaded CS-NPs is a promising approach for effective pain management.     

Perspectives of nanoemulsion assisted oral delivery of docetaxel for improved chemotherapy of cancer

Abstract

Context: Nanoemulsions (NE) are one of the robust delivery tools for drugs due to their higher stability and efficacy.

Objectives: The purpose of present investigation is to develop stable, effective and safe NE of docetaxel (DTX).

Methods: Soybean oil, lecithin, Pluronic F68, PEG 4000 and ethanol were employed as excipients and NEs were prepared by hot homogenization followed by ultra-sonication. NEs were optimized and investigated for different in vitro and in vivo parameters viz. droplet size, poly dispersity index, charge; zeta potential, drug content and in vitro drug release, in vitro cytotoxicity, in vitro cell uptake and acute toxicity. Transmission electron microscopy was performed to study morphology and structure of NEs. Stability studies of the optimized formulation were performed.

Results: Droplet size, poly dispersity index, zeta potential, drug content and in vitro drug release were found to be 233.23?±?4.3?nm, 0.24?±?0.010, ?43.66?±?1.9?mV, 96.76?±?1.5%, 96.25?±?2.1%, respectively. NE F11 exhibited higher cell uptake (2.83 times than control) and strong cytotoxic activity against MCF-7 cancer cells (IC₅₀; 13.55?±?0.21?µg/mL at 72?h) whereas no toxicity or necrosis was observed with liver and kidney tissues of mice at a dose of 20?mg/kg. Transmission electron microscopy ensured formation of poly-dispersed and spherical droplets in nanometer range. NE F11 (values indicated above) was selected as the optimized formulation based on the aforesaid parameters.

Conclusion: Conclusively, stable, effective and safe NE was developed which might be used as an alternative DTX therapy.     

Novel solidified reverse micellar solution-based mucoadhesive nano lipid gels encapsulating miconazole nitrate-loaded nanoparticles for improved treatment of oropharyngeal candidiasis

Objective: To develop and evaluate solidified-reverse-micellar-solution (SRMS)-based oromucosal nano lipid gels for improved localised delivery of miconazole nitrate (MN).

Methods: Phospholipon^® 90G and Softisan^® 154 (3:7) were used to prepare SRMS by fusion. Solid lipid nanoparticles (SLNs, 0.25–1.0% w/w MN) formulated with the SRMS by high shear homogenisation were employed to prepare mucoadhesive nano lipid gels. Physicochemical characterisation, drug release in simulated salivary fluid (SSF) (pH 6.8) and anti-candidal activity were carried out.

Results: The SLNs were spherical nanoparticles, had mean size of 133.8?±?6.4 to 393.2?±?14.5?nm, low polydispersity indices, good encapsulation efficiency (EE) (51.96?±?2.33–67.12?±?1.65%) and drug loading (DL) (19.05?±?2.44–24.93?±?1.98%). The nano lipid gels were stable, spreadable, pseudoplastic viscoelastic mucoadhesive systems that exhibited better prolonged release and anti-candidal properties than marketed formulation (Daktarin^® oral gel) (p?Conclusion: This study has shown that SRMS-based nano lipid gels could be employed to prolong localised oromucosal delivery of MN.     

Curcumin-loaded lipid nanocarrier for improving bioavailability,stability and cytotoxicity against malignant glioma cells

Objective: In the present study, Curcumin (CU)-loaded nanocarrier (NC) such as nanoemulsion (NE) was developed with the objective of increasing its cytotoxicity and bioavailability through lymphatic transport by enhancing its solubility and intestinal permeability.

Materials and methods: Based on the area obtained in pseudoternary phase diagram, various % combination of Labrafac Lipophile WL 1349, Solutol HS 15, Transcutol HP and distilled water were selected. Formulations which passed physical stability studies were selected for further studies such as globule size, zeta potential, in vitro release, ex vivo permeation, in vitro lipolysis studies, bioavailability studies and cytotoxicity against glioblastoma cells (U-87).

Result and discussion: The optimized NC (NE-SB1) had small average globule diameter of 67?±?6 nm with zeta potential of ?37?±?2.5?mv which indicated long-term dispersion stability. During in vitro lipolysis study, the digestion rate of medium chain triglycerides increased with decreased globule diameter. Statistically significant difference was found in AUC_0?inf of NC formulation (p?<?0.05) compared to CU suspension. The relative bioavailability of NC was found 11.88?±?0.47 with respect to CU suspension. During cytotoxicity studies, IC₅₀ of CU solution on U87 cells was found 24.23?µM, while for the NE- SB1 it was 16.41?µM. The optimized formulation was found to be stable during 6 months of accelerated stability.

Conclusion: The overall results revealed that the CU-loaded NC is a very effective approach for enhancing the oral absorption of poorly water-soluble drug CU and have great potential for future clinical application.     

Fabrication and evaluation of lipid nanoparticulates for ocular delivery of a COX-2 inhibitor

Context: The unique physiological limitations of the eye have been assigned as reason of low bioavailability by conventional drug delivery systems. There is need of such drug carriers, which ensure improved bioavailability as well as patient compliance upon instillation into the eye.

Objective: The present investigation deals with development of solid lipid nanoparticles (SLNs) containing celecoxib (CXB) for treatment of ophthalmic inflammations.

Materials and methods: The SLNs were formulated by melt-emulsion sonication and low temperature-solidification process and evaluated for particle size, surface morphology, physicochemical properties, percentage drug incorporation efficiency, in vitro drug release, in vitro trans-corneal permeation, in vivo efficacy in ocular inflammation, stability study and gamma scintigraphy study to assess the residence of solid lipid nanoparticles over ocular surfaces.

Results: The SLNs were spherical and the optimized formulation had particle size of 198.77?±?7.5?nm, which is quite suitable for ocular applications. The maximum entrapment efficiency of 92.46?±?0.07% was achieved for formulation SLN 20. The permeation across the cornea was also significantly better than aqueous suspension (8.21?±?0.67 versus 4.61?±?0.71) at p?<?0.05.

Discussion and conclusion: The SLN formulations demonstrated improved performance of entrapped CXB while mitigating the key parameters of ocular inflammation in rabbits. The particulate formulations have exhibited prolonged retention over ocular surfaces as evident from results of gamma scintigraphy using ^99mTc labeled SLNs.     

PEG-PLGA- hybrid nanoparticles loaded with etoricoxib – phospholipid complex for effective treatment of inflammation in rat model

The aim of the present study was to increase the bioavailability of the etoricoxib by making PEG-PLGA-Hybrid nanoparticles using emulsion solvent evaporation method. Then the prepared nanoparticles were further characterised using TEM, particle size, PDI, zeta potential, encapsulation efficiency and drug release study. Lipid (Phospholipon 90-G) and drug thermal behaviour were studied using DSC, TGA. The results of optimised formulation of Particle size, PDI and zeta potential was found 216.6?±?4.0?nm, 0.24?±?0.19 and +36.3?±?1.9?mV. Encapsulation efficiency was found in the range of 77.15% w/v to 93.88% w/v. In-vivo study shows that the optimised formulation at a particular dose decreases the swelling index and number of writhes. Stability study indicated that the nanoparticles can be stored at a temperature of 4?±?2?°C/60?±?5% RH in well-closed container, away from heat and damp places. The prepared formulation has significantly increased the bioavailability of etoricoxib via oral administration.     

Development and optimization of polymeric nanoparticles of antitubercular drugs using central composite factorial design*

Objective: The objective of the present study was to develop sustained release biodegradable polymeric nanoparticles (PNs) of two anti-tubercular drugs (ATDs), rifampicin (RIF) and isoniazid (INH) using circumscribed central composite factorial design (CCD) and evaluate in vivo uptake potential using rhodamine labeled PNs (RPNs).

Methods: CCD was employed to study the influence of independent formulation factors, drug:polymer ratio (D:P) and surfactant concentration (SC), on dependent physicochemical characteristics, particle size (PS), polydispersity index (PI) and percentage entrapment efficiency (%EE) of the drugs. Optimized PNs prepared using response surface methodology (RSM) were evaluated for in vitro kinetics at endosomal macrophage pH 5.2 and physiological pH 7.4 and in vivo targeting potential in peritoneal macrophages (PMs) by fluorescence microscopy (FM) and confocal laser scanning microscopy (CLSM).

Results: Optimized PNs exhibited spherical and porous surface with a mean PS of 202 nm, PI of 0.178, zeta potential of -25.49 mV and %EE of 76.12% and 54.25% for RIF and INH, respectively.

Conclusions: Highly hydrophilic INH could be encapsulated with lypophilic RIF with efficiency. In vivo uptake studies of RPNs in PMs suggested endocytosis of RPNs without any surface adsorption phenomenon. Hence, further studies need to be performed for establishing the pharmacokinetic potential of PNs.