Fabrication and optimization of chitosan-g-m-PEG-NH2 copolymer for advanced glioblastoma therapy using surface engineered lentinan loaded nanovesicles for nasal delivery.

Glioblastoma multiforme (GBM) exhibits a high mortality with an incidence rate of 3-5 per 100,000 each year, which demands existence of newer approach for its treatment. The current study focuses on synthesis of novel lipidic nanovesicles (LNs) loaded with highly potent macromolecule Lentinan (LNT) and surface modified with methoxy poly (ethylene glycol; PEG) amine (m-PEG-NH2)-grafted-chitosan (CS) for intranasal delivery. The grafting procedure was optimized using Box Behnken design (BBD) to limit the use of organic solvents. The fabricated polymer showed enhanced aqueous solubility, biodegradability and mucoadhesion, resulting in higher nasal mucosa permeation (z = 53.52 µm). The presence of PEG enabled the sustained release of LNT till 48 h and assisted in achieving higher accumulation of LNT in CSF (41.7 ± 3.1 µg/mL) and a higher brain targeting potential of 96.3 ± 2.31 % (p < 0.05). In-vitro cellular studies showed the enhanced anti-GBM effect of LNT on U87 MG cells by reducing the cell viability (~2 times reduction in IC50 value) accompanied with large number of cells undergoing late apoptosis and death (p < 0.05) because of the higher cellular uptake (63.22 ± 3.01 ng/100 cells) of novel formulation. The copolymer comprising LNs were biocompatible, stable and can be used as an effective tool in the management of GBM.

A bioanalytical assay for estimation of thymoquinone in rats cerebrospinal fluid and brain tissues of nasally administrated thymoquinone loaded lipo-polymeric nanoshells and its pharmacokinetic profiling.

Thymoquinone (TH) has been one of the major phytochemical used in the treatment of cancers since long time, especially in the management of glioblastoma multiforme (GBM). The formulation of lipo-polymeric nanoshells (LPNs) and their nasal delivery are fascinating approaches for overcoming the drawbacks of low solubility and poor bioavailability of TH. Hence targeting LPNs to the brain requires a validated bioanalytical method for the assessment of TH concentration in Cerebrospinal fluid (CSF) and brain tissue homogenates (BTH). Therefore, the current work focuses on the development and validation of high-performance liquid chromatography (HPLC) method in CSF by employing nasal simulated fluid (NSF) as one of the major components of the mobile phase. The developed method was checked for linearity in the range of 0.05 to 1.6 µg/mL, having an r2 value of 0.999 with mean % recovery >95% and % RSD values below <2.0%. The developed method gave a clear separation of TH at 6.021 ± 0.17 min with an internal standard at 4.102 ± 0.09 min and a CSF spike at 2.170 ± 0.12 min. The developed method assisted in determining the in-vitro and in-vivo drug release study of LPNs, pharmacokinetic profiling, qualitative in-vivo brain uptake study, in-vitro cellular uptake, and generating stability data of formulated LPNs proposed for intranasal administration in rats.

Development and characterization of amphotericin B nanoemulsion-loaded mucoadhesive gel for treatment of vulvovaginal candidiasis.

Despite being recognized as the "gold standard" for treating azole-resistant vulvovaginal candidiasis, amphotericin B (AmB), an amphoteric molecule, has not been widely used due to serious issues with solubility and permeability. In light of the aforementioned, the objective of the present study was to increase AmB's therapeutic efficacy by formulating it into an o/w nanoemulsion (AmB-NE) system. Furthermore, to facilitate AmB-NE's retention within the vaginal cavity, it was loaded into a mixture of Carbopol® 974P and Aloe vera-based gel (CA gel). Briefly, in the present study, a kinetically stable batch of formulated AmB-NE having a globule size of 76.52 ± 3.11 nm, PDI of 0.342 ± 0.032, and zeta potential of -22.32 ± 0.88 mV was incorporated into the CA gel base. This AmB-NE loaded gel (AmB-NE gel) exhibited a non-Fickian/anomalous diffusion from the hydrophilic matrix. The texture analysis of AmB-NE gel revealed that the prepared gel was a non-drip, soft, easy to spread, and sufficiently cohesive gel that could reside in the vaginal cavity, which was confirmed by our ex-vivo retention test, which revealed that AmB-NE loaded gel could stay in the vaginal cavity for approximately 11 h. Ex-vivo skin permeation studies revealed that AmB-NE is 4.26 times more permeable than AmB-coarse gel, implying that AmB-NE facilitates AmB entry into the vaginal epithelial layers. Furthermore, in-vivo vaginal lavage studies revealed that AmB-NE gel permeated 7.03-fold more than AmB-coarse gel. Prepared AmB-NE gel was stable in refrigerated condition and showed no histopathological toxicity. Thus, the present study suggests that AmB-NE gel could eliminate the existing problem of AmB and that it could serve as an alternative option to treat vulvovaginal candidiasis.

N,N,N­trimethyl chitosan modified flaxseed oil based mucoadhesive neuronanoemulsions for direct nose to brain drug delivery.

Here we fabricated flaxseed oil-based neuronanoemulsions (NNEs) which were further surface-modified with a mucoadhesive polymer, N,N,N­trimethyl chitosan (TMC) to form mucoadhesive neuronanoemulsions (mNNEs). The NNEs were loaded with high partitioning ropinirole-dextran sulfate (ROPI-DS) nanoplex and fabricated using hot high-pressure homogenization (HPH) technique. NNEs were optimized using Central Composite experimental design. TMC modified mNNE have not been prepared yet for direct nose to brain drug delivery. Here, an objective to provide controlled drug release with prolonged residence on the nasal mucosa for the treatment of Parkinson's disease (PD) is at prime consideration. Enhanced brain targeting through BBB bypass drug delivery, improved therapeutic efficacy through enhanced retention of mNNE formulation over nasal mucosal membrane, reduced dose and frequency of administration, and safety were further expected outcomes of this experiment. The mNNE formulation was subjected to 6 month stability assessment. The mNNE formulation was administered to the Swiss albino mice model via intranasal route and both, the plasma and brain pharmacokinetics were estimated. The in vivo studies performed on mice exhibited high brain targeting efficiency of mNNE formulation through nose to brain delivery via olfactory pathway. The prepared intranasal mNNEs could be on the clinics, if investigated more for behavioral and neurotoxicity studies.

Xyloglucan: A functional biomacromolecule for drug delivery applications.

The near future of drug delivery system would lie in the search of a versatile and innocuous material, based mostly on the natural resources. The tamarind seed xyloglucan (XG) is a natural neutral hemicellulose and a hydrophilic polysaccharide consisting of a main chain of glucan backbone with xylose and galactose side chains. XG is endowed with idiosyncratic mucoadhesive and in situ gelling properties which rated XG as an attractive, functional polymer for numerous drug delivery applications. In milieu of this, the present review is designed to underline the plausible potential of XG or XG-based systems in drug delivery. The feasibility of surface-tailoring, the flexibility of chemical-modification, and the possibility as ligand-conjugations grant XG an extraordinary consideration in the scientific territory. The authors are hopeful that the versatility of XG would meet the expectations of regulatory authorities and the XG-based products will serve the therapeutic needs of the community in the future, if sufficiently investigated and promising outcomes are obtained in human subjects.

N,N,N-Trimethyl chitosan: An advanced polymer with myriad of opportunities in nanomedicine.

N,N,N-trimethyl chitosan (TMC), a quaternized hydrophilic derivative of chitosan (CHT), outperformed the well-known solubility issues raised by CHT. The excellent properties offered by TMC provide it a significant edge for nanoparticle (NP) formation over other nanocarrier materials. Recently, TMC NPs have been applied to various fields like pharmaceutical, biomedical, biomaterials, and biotechnological field. The aim of this review is, therefore, to bring the TMC into the limelight so as to appraise it as an attractive functional polymer for nanomedicine applications which is facing oversight, at present, by regulatory agencies and manufacturers. The versatility of surface-tailoring, the capability of further chemical modifications, and the feasibility of ligand-conjugations in TMC polymer will further assist the scientists for reaching new dimensions in the nano-assembly of novel structures based on TMC.

Ropinirole-dextran sulfate nanoplex for nasal administration against Parkinson's disease: in silico molecular modeling and in vitro-ex vivo evaluation.

Dextran sulfate sodium (DS) was allowed to interact ionically with ropinirole hydrochloride (ROPI HCl, an anti-Parkinsonian agent) to synthesize self-assembled ROPI-DS nanoplex. The preliminary objective behind ROPI-DS complexation was to enhance the partitioning of ROPI HCl and thereby its encapsulation into nanocarriers and to improve the nasal membrane permeability. Molecular interactions were computed using in silico molecular modeling. Nanoplex were characterized for physicochemical and partitioning behavior. Optimized ROPI-DS nanoplex was further characterized by spectroscopic and thermal analysis, diffraction studies, morphological and histopathological analysis. In summary, ROPI-DS nanoplex represents a promising nanocarrier material for intranasal administration.

New nasal nanocomplex self-assembled from charged biomacromolecules: N,N,N-Trimethyl chitosan and dextran sulfate.

Although chitosan (CHT, a linear cationic polysaccharide) is biodegradable, biocompatible, non-toxic, and mucoadhesive in nature, the low solubility of CHT in aqueous and alkaline media limits its applicability in pharmaceutical and biomedical field. This necessitate the introduction of new chemically-modified derivatives of CHT those can surmount the solubility barrier. Herein, N,N,N-trimethyl chitosan (TMC), a quaternized hydrophilic derivative of CHT, was synthesized by two-step reductive methylation of CHT and characterized for (1)H NMR and zeta potential measurements. Polyelectrolyte complexes (PECs) based on TMC and dextran sulfate (DS) were prepared via ionic interactions between charged functional groups of former polysaccharides at different pH conditions (pH 5, 8, 10, and 12) and characterized for physicochemical (particle size and zeta potential) and solid- state characterizations (HR-TEM, SEM, FTIR, TGA and XRD). At alkaline pH conditions, the participant polymer chains (TMC and DS) are sufficiently close to form more stable PECs. The release efficiency was assessed after loading a model drug into optimized PEC formulation. Data indicated that the PECs fabricated at alkaline pH presents a reliable formulation for pharmaceutical and biomedical applications.

Polyelectrolyte complexes: mechanisms, critical experimental aspects, and applications.

The polyelectrolyte complexes (PECs) are versatile formulations formed by electrostatic interactions between oppositely charged biopolymers. PECs have been investigated widely by the researchers to explore the virtues of this formulation viz. high biocompatibility, excellent biodegradability, low toxicity, cost-effective, environment-friendly, and energy-efficient production. The prime object of the present review is to present the prominent features of PECs including mechanism of PEC formation, structural models of PECs, interactions involved in PEC formation, steps involved in PEC fabrication, factors affecting the formation of PECs and applications of PECs. The patents pertaining to PECs have briefly been tabulated as well.

Brain-blood ratio: implications in brain drug delivery.

INTRODUCTION: The brain-blood ratio is an important model correlating the brain-targeting ability of neurotherapeutics with the CNS pharmacokinetics, which need to be presented before the scientific community for exploration of its scientific worth. The purpose of this article is to bring this key concept and its precise discussion to the attention of the researchers. AREAS COVERED: Three major points are discussed herein: First, the significance of brain-blood ratio with respect to investigational neurotherapeutics, and carrier systems and correlation of its research findings with the brain targeting efficiency. Second, the various factors influencing the brain-blood ratio. Third, the various strategies for enhancing the brain-blood ratio. In addition, the benchmark criteria for CNS-likeness of drug molecules and the correlation of brain-blood ratio with brain targeting ability of neurotherapeutics have been tabulated. EXPERT OPINION: The brain-blood ratio (also referred to as the brain-plasma ratio) represents one of the tools available today for estimation of CNS pharmacokinetics. It is preferred over other complicated techniques (in situ brain perfusion and microdialysis) due to its ease of use and practicality. We are optimistic that the brain-blood ratio offers an excellent way of evaluating brain-targeting efficiency of neurotherapeutics effectively. In our opinion, it is a very fundamental aspect of brain bioavailability and needs to be presented in a precise way.

Controlled synthesis of N,N,N-trimethyl chitosan for modulated bioadhesion and nasal membrane permeability.

In an experiment to explore the bioadhesion, biocompatibility, and membrane permeation properties, the controlled synthesis of N,N,N-trimethyl chitosan (TMC) was carried out by two-step reductive methylation of chitosan (CHT). Methylation was confirmed by (1)H NMR (δ=3.1 ppm) and FTIR analysis (CH stretch at 1,485 cm(-1)). The TMC was further characterized by DSC, TGA, XRD, HR-TEM, SEM, and elemental analysis. Findings revealed improved solubility, enhanced viscosity, increased swelling index and higher molecular weight of TMC over CHT. Comparative evaluation validated increased bioadhesion potential, and improved ex vivo biocompatibility of TMC compared to CHT. Increased bioadhesion of TMC NPs over CHT NPs can be attributed to the strong electrostatic interactions between cationic amino groups with anionic sialic and sulfonic acid moieties contained in the mucin of the nasal mucus. Ex vivo biocompatibility studies suggested that the NP formulations of both biopolymers were biocompatible and could be applied safely on the nasal epithelium. Ex vivo permeation studies executed on excised cattle nasal mucosa illustrated improved permeability of TMC NPs over CHT NPs. In the author's opinion, two-step reductive methylation of CHT could be an attractive strategy to improve its solubility, bioadhesion, and permeation characteristics without affecting biocompatibility across the mucosal surfaces.

Nanotechnology-mediated nose to brain drug delivery for Parkinson's disease: a mini review.

Nose to brain delivery of neurotherapeutics have been tried by several researchers to explore the virtues of this route viz. circumvention of BBB, avoidance of hepatic metabolism, practicality, safety, ease of administration and non-invasiveness. Nanoparticle (NP) therapeutics is an emerging modality for the treatment of Parkinson's disease (PD) as it offers targeted delivery and enhances the therapeutic efficacy and/or bioavailability of neurotherapeutics. This review presents a concise incursion into the nanomedicines suitable for PD therapy delivered via naso-brain transport. Clinical signs of PD, its pathophysiology, specific genetic determinants, diagnosis and therapy involved have been hashed out. Properties of brain-targeting NPs, transport efficacy and various nanocarriers developed so far also been furnished. In our opinion, nanotechnology-enabled naso-brain drug delivery is an excellent means of delivering neurotherapeutics and is a promising avenue for researchers to develop new formulations for the effective management of PD.

Box-Behnken study design for optimization of bicalutamide-loaded nanostructured lipid carrier: stability assessment.

Bicalutamide (BCM) is an anti-androgen drug used to treat prostate cancer. In this study, nanostructured lipid carriers (NLCs) were chosen as a carrier for delivery of BCM using Box-Behnken (BB) design for optimizing various quality attributes such as particle size and entrapment efficiency which is very critical for efficient drug delivery and high therapeutic efficacy. Stability of formulated NLCs was assessed with respect to storage stability, pH stability, hemolysis, protein stability, serum protein stability and accelerated stability. Hot high-pressure homogenizer was utilized for formulation of BCM-loaded NLCs. In BB response surface methodology, total lipid, % liquid lipid and % soya lecithin was selected as independent variable and particle size and %EE as dependent variables. Scanning electron microscopy (SEM) was done for morphological study of NLCs. Differential scanning calorimeter and X-ray diffraction study were used to study crystalline and amorphous behavior. Analysis of design space showed that process was robust with the particle size less than 200 nm and EE up to 78%. Results of stability studies showed stability of carrier in various storage conditions and in different pH condition. From all the above study, it can be concluded that NLCs may be suitable carrier for the delivery of BCM with respect to stability and quality attributes.

Novel surface modified polymer-lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation.

Here we report fabrication and evaluation of novel surface modified polymer-lipid hybrid nanoparticles (PLN) as robust carriers for intranasal delivery of ropinirole hydrochloride (ROPI HCl). Sustained release, avoidance of hepatic first pass metabolism, and improved therapeutic efficacy are the major objectives of this experiment. PLN were fabricated by emulsification-solvent diffusion technique and evaluated for physicochemical parameters, in vitro mucoadhesion, in vitro diffusion, ex vivo permeation, mucosal toxicity and stability studies. Box-Behnken experimental design approach has been employed to assess the influence of two independent variables, viz. surfactant (Pluronic F-68) and charge modifier (stearylamine) concentration on particle size, ζ-potential and entrapment efficiency of prepared PLN. Numerical optimization techniques were used for selecting optimized formulation sample, further confirmed by three dimensional response surface plots and regression equations. Results of ANOVA demonstrated the significance of suggested models. DSC and SEM analysis revealed the encapsulation of amorphous form of drug into PLN system, and spherical shape. PLN formulation had shown good retention with no severe signs of damage on integrity of nasal mucosa. Release pattern of drug-loaded sample was best fitted to zero order kinetic model with non-Fickian super case II diffusion mechanism. In vivo pharmacodynamic studies were executed to compare therapeutic efficacy of prepared nasal PLN formulation against marketed oral formulation of same drug. In summary, the PLN could be potentially used as safe and stable carrier for intranasal delivery of ROPI HCl, especially in treatment of Parkinson's disease.

Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targeting.

INTRODUCTION: The blood-brain barrier (BBB) represents a stringent barrier for delivery of neurotherapeutics in vivo. An attempt to overcome this barrier is represented by the direct transport of drugs from the nose to the brain along the olfactory and trigeminal nerve pathways. These nerve pathways initiate in the nasal cavity at olfactory neuroepithelium and terminate in the brain. An enormous range of neurotherapeutics, both macromolecules and low molecular weight drugs, can be delivered to the central nervous system (CNS) via this route. AREAS COVERED: Present review highlights the literature on the anatomy-physiology of the nasal cavity, pathways and mechanisms of neurotherapeutic transport across nasal epithelium and their biofate and various strategies to enhance direct nose to brain drug delivery. The authors also emphasize a variety of drug molecules and carrier systems delivered via this route for treating CNS disorders. Patents related to direct nose to brain drug delivery systems have also been listed. EXPERT OPINION: Direct nose to brain drug delivery system is a practical, safe, non-invasive and convenient form of formulation strategy and could be viewed as an excellent alternative approach to conventional dosage forms. Existence of a direct transport route from the nasal cavity to the brain, bypassing the BBB, would offer an exciting mode of delivering neurotherapeutic agents.

Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach.

Present investigation deals with intranasal delivery of ropinirole hydrochloride (ROPI HCl), loaded in solid lipid nanoparticles (SLNs). Prime objectives of this experiment are avoidance of hepatic first pass metabolism and to improve therapeutic efficacy in the treatment of Parkinson's disease. SLNs were fabricated by emulsification-solvent diffusion technique. A 3(2)-factorial design approach has been employed to assess the influence of two independent variables, namely Pluronic F-68 and stearylamine concentration on particle size, ζ-potential and entrapment efficiency of prepared SLNs. Prepared samples were further evaluated for in vitro drug diffusion, ex vivo drug permeation, histopathological and stability studies. Differential scanning calorimetry analysis revealed the encapsulation of amorphous form of drug into lipid matrix, while scanning electron microscopy studies indicated the spherical shape. Fabricated SLNs had shown no severe signs of damage on integrity of nasal mucosa. Release pattern of prepared drug-loaded sample was best fitted to zero-order kinetic model with non-Fickian super case II diffusion mechanism. In vivo pharmacodynamic studies were carried out to compare therapeutic efficacy of prepared nasal formulation against marketed oral formulation. Results of analysis of variance demonstrated the significance of suggested model. Three-dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. Our findings suggested the feasibility of investigated system for intranasal administration.

Solubility Enhancement of Raloxifene Using Inclusion Complexes and Cogrinding Method.

The objective of the present work was to enhance the solubility and dissolution of practically water-insoluble drug raloxifene HCl (RLX), for the same two approaches that were used. In the first approach, drug was kneaded with hydroxypropyl-ß-cyclodextrin (HPßCD), and in the second one drug was cogrinded with modified guar gum (MGG). The drug-cyclodextrin complex and drug-MGG cogrind mixtures were characterized by differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy, and Fourier transform infrared spectroscopy. The solubility and dissolution study reveals that solubility and dissolution rate of RLX remarkably increased in both methods. It was concluded that the prepared inclusion complex showed a remarkable increase in solubility and dissolution of poorly water-soluble drug raloxifene. In the cogrinding mixture, a natural modified gum is used as a surfactant and enhances the solubility and dissolution of RLX without requiring addition of organic solvent or high temperature for its preparation; thus, process is less cumbersome and cost effective. But when both methods were compared; HPßCD complexation method showed significant enhancement of drug solubility.

Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX), which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV). The optimized ratio for preparing a solid dispersion (SD) of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

O objetivo do presente trabalho foi aumentar a solubilidade e taxa de dissolução do cloridrato de raloxifeno (RLX), que é pouco solúvel em água. A solubilidade do RLX aumentou com o aumento da concentração de hidroxipropilmetilcelulose (HPMC E5 LV). A proporção otimizada para a preparação de uma dispersão sólida (DS) de RLX com HPMC E5 LV utilizando o método de fusão induzida por microondas foi de 1:5 (p/p). A energia do microondas foi usada para preparar DS. O HPMC E5 LV foi utilizado como veículo hidrofílico para aumentar a solubilidade e a taxa de dissolução de RLX. Após o tratamento por microondas, o polímero hidrofílico e o fármaco são fundidos em conjunto, sendo o fármaco convertido da forma cristalina para a amorfa. Confirmou-se por meio de microscopia eletrônica de varredura (MEV), calorimetria exploratória diferencial (DSC) e difração de raios X do pó (PXRD). Estes resultados sugerem que o método de microondas é simples e eficiente para a preparação de DS. A solubilidade e taxa de dissolução de DS foram aumentadas, significativamente, em comparação com RLX puro devido às propriedades tensoativas e umectantes de HPMC E5 LV e à formação de dispersões moleculares do fármaco em HPMC E5 LV. Concluiu-se que a solubilidade e a taxa de dissolução de RLX foram significativamente aumentadas quando a DS do fármaco é preparada utilizando o método de fusão induzida por microondas.

Solid lipid nanoparticles of ondansetron HCl for intranasal delivery: development, optimization and evaluation.

The present investigation deals with the development and statistical optimization of solid lipid nanoparticles (SLNs) of ondansetron HCl (OND) for intranasal (i.n.) delivery. SLNs were prepared using the solvent diffusion technique and a 2(3) factorial design. The concentrations of lipid, surfactant and cosurfactant were independent variables in this design, whereas, particle size and entrapment efficiency (EE) were dependent variables. The particle size of the SLNs was found to be 320-498 nm, and the EE was between 32.89 and 56.56 %. The influence of the lipid, surfactant and cosurfactant on the particle size and EE was studied. A histological study revealed no adverse response of SLNs on sheep nasal mucosa. Transmission electron microscopic analysis showed spherical shape particles. Differential scanning calorimetry and X-ray diffraction studies indicated that the drug was completely encapsulated in a lipid matrix. In vitro drug release studies carried out in phosphate buffer (pH 6.6) indicated that the drug transport was of Fickian type. Gamma scintigraphic imaging in rabbits after i.n. administration showed rapid localization of the drug in the brain. Hence, OND SLNs is a promising nasal delivery system for rapid and direct nose-to-brain delivery.

Formulation and evaluation of Nimodipine-loaded solid lipid nanoparticles delivered via lymphatic transport system.

In an attempt to increase oral bioavailability and to target intestinal lymphatic transport system, Nimodipine loaded solid lipid nanoparticles (NMD-SLNs) were prepared. Nimodipine (NMD) is highly lipophilic antihypertensive drug having (logP 3.41) and 13% oral bioavailability. NMD-SLNs were prepared with palmitic acid (PA), poloxamer 188 and soya lecithin as a lipid, surfactant and co-surfactant respectively using high pressure homogeniser. A (2(3)) factorial design was employed; three factors such as lipid, surfactant and co-surfactant concentration were used. Parameters investigated includes particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency (EE %), drug loading efficiency (LE %), in vitro drug release of the SLNs. Optimised SLNs (F8) had particle size of 116±21 nm, zeta potential of -10±(-4.8) mV, EE of 93.66±9.72% and cumulative drug release of 87.52±2.54% in 10 h. The pharmacokinetic study of optimised SLNs conducted in male Albino Wistar rats showed 2.08-fold increase in relative bioavailability than that of NMD solution, when administered orally. Differential scanning calorimetry study revealed absence of any chemical interaction between NMD and PA while SEM study confirmed the non spherical shape of optimised SLNs. Accelerated stability studies showed that there was no significant change in the mean particle size and PDI after storage at 25±2°C/60±5% RH for the period of three months. Due to enhanced bioavailability, these NMD-SLNs are considered to be promising vehicles for oral delivery.