Browsing by Author "Jindal, Anil B."

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Asymmetric lipid–polymer particles (LIPOMER) by modified nanoprecipitation: role of non-solvent composition
(Elsevier, 2015-07) Jindal, Anil B.
Asymmetric lipid polymer nanostructures (LIPOMER) comprising glyceryl monostearate (GMS) as lipid and Gantrez AN 119 (Gantrez) as polymer, revealed enhanced splenic accumulation. In the present paper, we attempt to explain the formation of asymmetric GMS LIPOMER using real time imaging. Particles were prepared by precipitation under static conditions using different non-solvent phase compositions. The process was video recorded and the videos converted to time elapsed images using the FFmpeg 0.10.2 software at 25frames/sec. Non-solvent compositions comprising >30% of IPA/Acetone revealed significant stranding of the solvent phase and slower onset of precipitation(2–6 s). At lower concentrations of IPA and acetone, and in non-solvent compositions comprising ethanol/water the stranding phenomenon was not evident. Further, rapid precipitation(<1 s) was evident. Nanoprecipitation based on the Marangoni effect is a result of diffusion stranding, interfacial turbulence, and mass transfer of solvent and non-solvent resulting in solute precipitation. Enhanced diffusion stranding favored by high interaction of GMS and Gantrez(low ΔPol), and the low solubility parameter(Δδtotal) and high mixing enthalpy(ΔHM) of GMS in IPA resulted in droplets with random shapes analogous to an amoeba with pseudopodia, which on precipitation formed asymmetric particles. Asymmetric particles could be readily designed through appropriate selection of solutes and non-solvent phase by modified nanoprecipitation.
Biopolymers for enzyme immobilization
(Wiley, 2024-10) Jindal, Anil B.
Enzyme immobilization has shown promising applications in different fields, including pharmaceuticals, chemistry, and medicine. Immobilized enzymes are more stable, recoverable, and robust than their free forms. Enzymes act as biocatalysts for several reactions, however, there is an important role of biopolymers, which act as supporting materials. Synthesis of new functionalized supporting materials from conventional polymers or using the novel technique for immobilization can serve the multiple demands of industries to ease the multi-step process of biocatalysis. In enzyme immobilization, numerous factors play a crucial role, such as the selection of support materials, optimization of pH, temperature, reaction time, and concentration of enzyme. Moreover, the present chapter provides a compiled summary of enzyme immobilization methods or techniques, biopolymers, and their features along with newer development as well as application in the same field.
Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment
(Bentham Science, 2022) Jindal, Anil B.
The commensal microbiota is known to regulate host physiology. Dysbiosis or compromised resilience in the microbial ecology is related to the impending risk of cancer. A potential link between cancer and microbiota is indicated by a lot of evidence. The current review explores in detail the various links leading to and /or facilitating oncogenesis, providing sound reasoning or a basis for its utilization as potential therapeutic targets. The present review emphasizes the existing knowledge of the microbiome in cancer and further elaborates on the factors, like genetic modifications, effects of dietary components, and environmental agents, that are considered to assess the direct and indirect effect of microbes in the process of oncogenesis and on the host’s health. Strategies modulating the microbiome and novel biotherapeutics are also discussed. Pharmacomicrobiomics is one such niche accounting for the interplay between the microbiome, xenobiotic, and host responses, which is also looked upon. The literature search strategy for this review was conducted by following the methodology of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The method includes the collection of data from different search engines, like PubMed, ScienceDirect, SciFinder, etc., to get coverage of relevant literature for accumulating appropriate information regarding microbiome, cancer, and their linkages.
Compression
(Springer, 2023-07) Jindal, Anil B.
Compaction of powder involves compression and consolidation of the solids on the application of pressure. The forces involved in these processes play an important role in the design and development of solid oral dosage forms including tablets, filling of the hard-gelatin capsule, and in the handling of powders. Assessment of the forces on punches, axial forces, radial forces, frictional forces, and ejection forces gives us information regarding the compaction behaviour of the powder. Several mathematical terms to describe the compaction processes are studied such as the heckle plot. Optimizing the parameters that affect these forces would produce a product of the desired quality. In this chapter, we have discussed in detail about compression, consolidation, and forces involved in compaction and their impact on the quality of the product.
Current status of dolutegravir delivery systems for the treatment of HIV-1 infection
(Elsevier, 2022-10) Jindal, Anil B.
According to the World Health Organization (WHO), an estimated 37.7 million people were living with HIV in 2020. Dolutegravir is recommended as the first line and second line antiretroviral drug for the treatment of HIV-1 infection in combination with NRTI and NNRTI in all populations. It is the second-generation integrase strand transfer inhibitor which is preferred over elvitegravir and raltegravir because of enhanced elimination half-life, reduced dosing frequency, and higher barrier to resistance. Dolutegravir is available in the market in the form of oral tablet for the treatment of HIV-1 infection in all populations. Several other formulations including long-acting gastroretentive dosage form, long-acting injectables, in-situ forming implants, nasal, and vaginal formulations have also been reported which have shown promising results in the treatment of HIV-1 infection in preclinical studies. In the future, clinical translation of the long-acting formulations will enhance the adherence to the therapy by the patient and bring us closer to the goal of eradicating HIV as an epidemic by 2030. The present review elaborates on different strategies which have been reported for the delivery of dolutegravir in adults and paediatrics.
Current status of Liraglutide delivery systems for the management of type 2 diabetes mellitus
(Springer, 2025-09) Jindal, Anil B.
Diabetes is a metabolic disorder of increasing global concern. Characterized by constantly elevated levels of glucose, severe β-cell dysfunction, and insulin resistance, it is the cause of a major burden on patients if not managed with therapeutic and lifestyle changes. The human body is slowly developing tolerance to many marketed antidiabetic drugs and the quest for the discovery of newer molecules continues. Liraglutide is a prominent GLP-1 receptor agonist which is administered daily via subcutaneous injection. In addition to lowering HbA1c levels, it is also known for promoting weight loss and improving cardiovascular outcomes. A variety of novel formulation strategies have been explored to improve its bioavailability and patient compliance. To address these limitations, various advanced drug delivery systems have been investigated, including polymeric nanoparticles, lipid-based nanocarriers, biodegradable microparticles, hydrogels, and dissolvable microneedles. These systems aim to prolong drug release, enhance mucosal penetration, increase stability, and reduce dosing frequency. While many of these platforms show promise in preclinical and early clinical studies, critical translational barriers remain. These include challenges in large-scale manufacturing, ensuring formulation sterility, achieving regulatory approval, and maintaining stability during storage and distribution.
Current Status of Therapeutic Peptides for the Management of Diabetes Mellitus
(Springer, 2024-02) Jindal, Anil B.
Diabetes mellitus (DM) is a chronic endocrine disorder with lifelong implications. The prevalence of this condition is steadily increasing, emphasizing the need for effective management to maintain healthy blood sugar levels and mitigate associated complications. While various antidiabetic medications are available, individuals with type 1 diabetes rely on lifelong insulin therapy, and those with type 2 diabetes may also require it if other oral treatments prove ineffective. This study focuses on peptide-based therapies approved for diabetes management, including insulin, incretin mimetics (GLP-1, GLP-1 analogues, and GIP analogues), and amylin analogues. The advent of peptide-based therapeutics represents significant progress in diabetes management. Peptides consist of short sequences of amino acids and offer immense potential for treating the complicated pathophysiology of diabetes. They exhibit higher potency and specificity, although their short half-life in the body, cost, and instability are notable drawbacks. Modification of the peptide chain structure and various formulation strategies to prolong their plasma circulation time and reduce the frequency of dosing aim to minimize drawbacks associated with the peptide molecules. Continuous advancements in drug delivery strategies have also resulted in the greater therapeutic efficacy of peptides, better disease management, and improved quality of life for patients
Development and validation of reverse-phase high-performance liquid chromatographic (RP-HPLC) method for quantification of Efavirenz in Efavirenz-Enfuvirtide co-loaded polymer-lipid hybrid nanoparticles
(Elsevier, 2019-10) Jindal, Anil B.
The objective of present work was to develop rapid, sensitive, selective, accurate and precise RP-HPLC method for analysis of Efavirenz from combination anti-HIV drug (Efavirenz-Enfuvirtide) incorporated into polymer-lipid hybrid nanoparticles (PLN). Chromatographic separation of Efavirenz was performed on Waters Spherisorb® 5 μm ODS (C18) column (4.6 x 250 mm) with acetonitrile and 10 mM phosphate buffer pH 6.8 (70:30, v/v) as mobile phase. The UV detection wavelength was 246 nm. The method was found to be linear between the concentration range of 500–20000 ng/ml with 160 ng/ml and 480 ng/ml as limit of detection and limit of quantitation respectively. Heteroscedasticity of calibration curve responses was minimized using weighted least square regression analysis. The method was found to be specific for analysis of Efavirenz in presence of Enfuvirtide (a fusion inhibitor peptide), formulation excipients and release media, accurate (average recovery rate: 99.9 ± 9.39%) and precise (%RSD < 2%). The validated RP-HPLC method could be effectively utilized to determine % entrapment efficiency (%EE), % drug loading (%DL), % cumulative drug release and drug content of Efavirenz from Efavirenz-Enfuvirtide co-loaded PLN.
Development of cationic Isometamidium chloride loaded long-acting lipid nanoformulation: optimization, cellular uptake, pharmacokinetics, biodistribution, and immunohistochemical evaluation
(Elsevier, 2021-12) Jindal, Anil B.
The aim of the present work involved the development and evaluation of long-acting Isometamidium chloride (ISMM)-Docusate sodium (DS) complex loaded lipid nanoparticles (LA ISMM-DS LNP). The development involved screening various anionic complexing agents, including DS, dextran sulphate, and sodium alginate. Anionic DS was selected to synthesize hydrophobic ionic complex (ISMM-DS HIC), which was loaded into lipid nanoparticles (LA ISMM-DS LNP) by in situ complexation followed by the solvent evaporation method. 35-5-folds increase in the drug loading of hydrophilic cationic ISMM within nanoparticles was observed due to ISMM-DS HIC. The LA ISMM-DS LNP were non-hemolytic (0–2.52%), cytocompatible (80.6–47.5% cell viability), and enhanced THP-1 cellular uptake (2.3-folds higher) compared with free ISMM. The LA ISMM-DS LNP engender protracted in vivo plasma drug concentration for seven days with enhanced AUC0-ꝏ, MRT0-ꝏ, and t1/2, along with reduced Cl compared with free ISMM. Interestingly, the amount of ISMM was 2.9-, 4.2- and 2.0-folds higher in target reticuloendothelial (RES) organs like liver (Kupffer cells), spleen (spleenotropic macrophages and 15% T-lymphocytes), and lymph nodes (75% T-lymphocytes), respectively in LA ISMM-DS LNP group compared with free ISMM. Furthermore, LA ISMM-DS LNP caused higher peripheral blood mononuclear cells (PBMC) infiltration with diminished toxicity and inflammation. Therefore, the in vitro and in vivo studies predicted enhanced safety and efficacy of LA ISMM-DS LNP compared with free ISMM. To conclude, successfully developed LA ISMM-DS LNP would elicit a tremendous clinical potential for treatment and prevention against trypanosomiasis.
Development of efavirenz loaded solid lipid nanoparticles: Risk assessment, quality-by-design (QbD) based optimisation and physicochemical characterisation
(Elsevier, 2017-06) Jindal, Anil B.
The purpose of this study was development and characterisation of efavirenz (EFZ) loaded solid lipid nanoparticles (SLN) using QbD approach. Quality target product profile of EFZ loaded SLN were defined and critical quality attributes were identified. SLN were prepared by nanoprecipitation method. Initially, feasibility of SLN formation was studied by using different lipids including glyceryl monostearate, stearic acid and surfactants such as poloxamer 188, tween 80, docusate sodium and sodium lauryl sulphate. A 32 factorial design was employed to optimize EFZ loaded SLN wherein acetone/methanol ratio in organic phase and surfactant concentration were selected as independent variables whereas particle size (PS) and %entrapment efficiency (EE) were selected as responses. PS of SLN was found to be varied from 167.77 to 1166 nm and %EE was in the range of 23.07–88%. DSC thermograms indicated the amorphous state of EFZ in the SLN. The FTIR studies confirmed no interaction among materials used in fabrication of SLN while NMR studies confirmed their incorporation in the SLN. Spherical shape of SLN was confirmed by TEM. This study suggests the importance of implementation of QbD approach for identifying critical process and formulation parameter in order to develop nano based pharmaceutical product.
Drying
(Springer, 2023-07) Jindal, Anil B.
Drying is a vital process in pharmaceutical formulation involving removal of moisture from solids by applying heat, thus resulting in both heat and mass transfer. The process when theoretically studied utilizes various terms such as absolute humidity, saturation humidity, dew point, relative humidity, drying capacity, wet bulb temperature and the dry bulb temperature which can be understood with the help of psychometric chart. The process of drying of solids when graphically plotted as drying rate versus moisture content is known as drying rate curve. The drying rate curve can be classified as initial adjustment period, constant rate period, first falling rate period and second falling rate period as per the trends of curve. Various types of equipment are used for drying the pharmaceutical solids. The most basic amongst them is a tray drier where the solids are kept on a tray and are dried with hot air. Whereas in fluidized bed dryer, the solids are dried by suspending in air by a constant stream of hot air. On the other hand, when the fluid content is higher, spray drying can be used where the mixture is pumped on a hot drying environment leading to atomization and further leaving particulate solid residue of the mixture. Freeze drying and vacuum drying are the specialized drying processes where drying is achieved by freezing samples or by reducing the pressure around the samples, thus resulting in drying without heating.
The effect of particle shape on cellular interaction and drug delivery applications of micro- and nanoparticles
(Elsevier, 2017-10) Jindal, Anil B.
Encapsulation of therapeutic agents in nanoparticles offers several benefits including improved bioavailability, site specific delivery, reduced toxicity and in vivo stability of proteins and nucleotides over conventional delivery options. These benefits are consequence of distinct in vivo pharmacokinetic and biodistribution profile of nanoparticles, which is dictated by the complex interplay of size, surface charge and surface hydrophobicity. Recently, particle shape has been identified as a new physical parameter which has exerted tremendous impact on cellular uptake and biodistribution, thereby in vivo performance of nanoparticles. Improved therapeutic efficacy of anticancer agents using non-spherical particles is the recent development in the field. Additionally, immunological response of nanoparticles was also altered when antigens were loaded in non-spherical nanovehicles. The apparent impact of particle shape inspired the new research in the field of drug delivery. The present review therefore details the research in this field. The review focuses on methods of fabrication of particles of non-spherical geometries and impact of particle shape on cellular uptake, biodistribution, tumor targeting and production of immunological responses.
Evaluation of Pharmacokinetics, Biodistribution, and Antimalarial Efficacy of Artemether-Loaded Polymeric Nanorods
(ACS, 2023) Jindal, Anil B.
Artemether oily injection is recommended for the treatment of severe malaria by the intramuscular route. The major limitations of the artemisinin combination therapy are erratic absorption from the injection site and high dosing frequency due to a very short elimination half-life of the drug. Advanced drug delivery systems have shown significant improvement in the current malaria therapy; the desired drug concentration within infected erythrocytes is yet the major challenge. Recently, we have reported the fabrication of artemether-loaded polymeric nanorods for intravenous malaria therapy which was found to be biocompatible with THP-1 monocytes and rat erythrocytes. The objective of the present study was the evaluation of pharmacokinetics, biodistribution, and antimalarial efficacy of artemether-loaded polymeric nanorods. Scanning electron microscopy and confocal microscopy studies revealed that both nanospheres and nanorods were adsorbed onto the surface of rat erythrocytes after an incubation of 10 min. After intravenous administration to rats, artemether nanorods showed higher plasma concentration and lower elimination rate of artemether when compared with nanospheres. The biodistribution studies showed that, at 30 min, the liver concentration of DiR-loaded nanospheres was higher than that of DiR-loaded nanorods after intravenous administration to BALB/c mice. The in vitro schizont inhibition study showed that both nanorods and nanospheres exhibited concentration-dependent parasitic inhibition, wherein at lower concentrations (2 ppm), nanorods were more effective than nanospheres. However, at higher concentrations, nanospheres were found to be more effective. Nanorods showed higher chemosuppression on day 5 and day 7 than nanospheres and free artemether when studied with the Plasmodium berghei mouse model. Moreover, the survival rate of P. berghei infected mice was also found to be higher after treatment with artemether nanoformulations when compared with free artemether. In conclusion, polymeric nanorods could be a promising next-generation delivery system for the treatment of malaria.
Evaluation of synergistic anti-inflammatory activity of selected natural products in combination with teriflunomide in LPS stimulated RAW 264.7 cells for rheumatoid arthritis treatment
(Elsevier, 2025-09) Jindal, Anil B.
Rheumatoid arthritis (RA) is an immune-mediated disorder that involves joints and synovial membrane, and requires combination therapy for effective management. Teriflunomide (TFD) belongs to Synthetic Disease-modifying antirheumatic drugs (DMARDs), prescribed either alone or in combination therapy. The combination of clinical drugs with natural products offers a promising strategy to enhance therapeutic efficacy and reduce the dose and thus ameliorate side effects. This study aims to evaluate the synergistic anti-inflammatory efficacy of TFD with selected natural products such as Andrographolide (ANG), Quercetin (QCN), Resveratrol (RES), Rutin (RUT) and Tanshinone IIA (TAN) in LPS-stimulated RAW264.7 cells. The initial screening was performed using nitric oxide (NO) assay to determine the IC50, with prior determination of the safest concentration range using the MTT assay. The study utilized a constant ratio design to assess synergy, employing the NO assay and calculating the combination index (CI), isobologram analysis, and dose reduction index (DRI). Among the tested combinations, QCN, RES, and TAN with TFD displayed low CI values and were evaluated for proinflammatory cytokines using ELISA. Notably, the combination of QCN and TFD showed significant synergistic activity with CI values of 0.470 and 0.607 (at Fa = 0.5) against TNF-α and IL-6, respectively. Intracellular reactive oxygen species (ROS) measurement with this combination revealed even greater synergistic activity, suggesting a promising approach for RA treatment.
Fabrication and evaluation of artemether loaded polymeric nanorods obtained by mechanical stretching of nanospheres
(Elsevier, 2021-08) Jindal, Anil B.
The objective of the present study was to prepare and evaluate artemether-loaded poly (lactic-co-glycolic acid) (PLGA) nanorods by mechanical stretching of nanospheres. Artemether-loaded PLGA nanospheres were prepared by the standard nanoprecipitation method. To prepare the nanorods, nanospheres (129 nm) were embedded in polyvinyl alcohol film. The film was stretched by using an in-house fabricated film stretching apparatus in one dimension at the rate of 10 mm/min in acetone or silicon oil. Nanorods were recovered by dissolving the film in Milli-Q-water after stretching. The effect of film thickness (100 µm vs 150 µm), the ratio of lactide to glycolide in PLGA (50:50 vs 75:25), extent of stretching (2x vs 4x), on the aspect ratio of the nanorods was studied. A sustained release of artemether was observed from both nanospheres and nanorods with almost 85% drug release at the end of 72 h. In cytotoxicity study, almost 90% cell viability was found when THP-1 cells were treated with artemether, nanospheres, and nanorods equivalent to 0.001 to 100 µg/mL of artemether. At all the concentrations of artemether, nanorods showed less haemolysis of RBCs than the nanospheres. Artemether-loaded PLGA nanorods could be successfully prepared by the film stretching method for intravenous delivery of antimalarial drugs.
Fluid Bed Processing Technology
(Springer, 2023-07) Jindal, Anil B.
Fluid bed processing technology is widely used in the pharmaceutical industry for the processing of multiparticulates. The chapter describes the theory of fluidization followed by the components of a fluidized bed processor and their functioning. Further, the formulation, process and equipment-related factors that affect product quality are described in detail. Being a complex process, the process scale-up principles of the processor are discussed.
Formulation strategies to overcome amphotericin B induced toxicity
(ACS, 2024-10) Jindal, Anil B.
Fungal infection poses a major global threat to public health because of its wide prevalence, severe mortality rate, challenges involved in diagnosis and treatment, and the emergence of drug-resistant fungal strains. Millions of people are getting affected by fungal infection, and around 3.8 million people face death per year due to fungal infection, as per the latest report. The polyene antibiotic AmB has an extensive record of use as a therapeutic moiety against systemic fungal infection and leishmaniasis since 1960. AmB has broad-spectrum fungistatic and fungicidal activity. AmB exerts its therapeutic activity at the cellular level by binding to fungal sterol and forming hydrophilic pores, releasing essential cellular components and ions into the extracellular fluid, leading to cell death. Despite using AmB as an antifungal and antileishmanial at a broad scale, its clinical use is limited due to drug-induced nephrotoxicity resulting from binding the aggregated form of the drug to mammalian sterol. To mitigate AmB-induced toxicity and to get better anti-fungal therapeutic outcomes, researchers have developed nanoformulations, self-assembled formulations, prodrugs, cholesterol- and albumin-based AmB formulations, AmB-mAb combination therapy, and AmB cochleates. These formulations have helped to reduce toxicity to a certain extent by controlling the aggregation state of AmB, providing sustained drug release, and altering the physicochemical and pharmacokinetic parameters of AmB. Although the preclinical outcome of AmB formulations is quite satisfactory, its parallel result at the clinical level is insignificant. However, the safety and efficacy of AmB therapy can be improved at the clinical stage by continuous investigation and collaboration among researchers, clinicians, and pharmaceutical companies.
Freeze-drying revolution: unleashing the potential of lyophilization in advancing drug delivery systems
(Springer, 2023-11) Jindal, Anil B.
Lyophilization also known as freeze-drying is a technique that has been employed to enhance the long-term durability of nanoparticles (NPs) that are utilized for drug delivery applications. This method is used to prevent their instability in suspension. However, this dehydration process can cause stress to the NPs, which can be alleviated by the incorporation of excipients like cryoprotectants and lyoprotectants. Nevertheless, the freeze-drying of NPs is often based on empirical principles without considering the physical–chemical properties of the formulations and the engineering principles of freeze-drying. For this reason, it is crucial to optimize the formulations and the freeze-drying cycle to obtain a good lyophilizate and ensure the preservation of NPs stability. Moreover, proper characterization of the lyophilizate and NPs is of utmost importance in achieving these goals. This review aims to update the recent advancements, including innovative formulations and novel approaches, contributing to the progress in this field, to obtain the maximum stability of formulations. Additionally, we critically analyze the limitations of lyophilization and discuss potential future directions. It addresses the challenges faced by researchers and suggests avenues for further research to overcome these limitations. In conclusion, this review is a valuable contribution to the understanding of the parameters involved in the freeze-drying of NPs. It will definitely aid future studies in obtaining lyophilized NPs with good quality and enhanced drug delivery and therapeutic benefits.
Implementing analytical quality by design in reversed phase-high performance liquid chromatography for simultaneous estimation of teriflunomide and quercetin: Applicability in dual drug loaded topical microemulsion
(Taylor & Francis, 2024-03) Jindal, Anil B.; Paul, Atish Tulshiram
The current study reports the development of a novel, robust, and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of teriflunomide (TFD) and quercetin (QCN) in dual drug-loaded microemulsion. TFD and QCN have been reported to exhibit anti-inflammatory effects by targeting various inflammatory mediators involved in the pathogenesis of rheumatoid arthritis (RA). This analytical method employs a risk-based approach and follows the principles of analytical quality by design (AQbD). The study involved preliminary screening trials and systematic risk analysis to identify critical method attributes, that significantly impact the critical quality attributes (CQAs). For the optimization of method,a face centered central composite design was utilized, and 16 experimental runs were performed using design expert software version 7.0.0. Chromatographic conditions were carefully optimized using AQbD, falling within the design space and consisting of ammonium acetate buffer (pH 3.5) and acetonitrile (60:40, % v/v) with a flow rate of 1.0 mL/min. An analytical Hibar Lichospher 100 RP-18e column (250 × 4.6 mm, 5 µm) was employed, with detection wavelength of 280 nm and 367 nm for TFD and QCN, respectively. The optimized method underwent validation according to ICH guidelines and demonstrating applicability for evaluating topical microemulsion.
In situ hybrid nano drug delivery system (IHN-DDS) of antiretroviral drug for simultaneous targeting to multiple viral reservoirs: An in vivo proof of concept
(Elsevier, 2017-04) Jindal, Anil B.
We report In situ hybrid nano drug delivery system (IHN-DDS) of nevirapine (NVP) for simultaneous targeting to multiple viral reservoirs. The IHN-DDS system was comprised of a preconcentrate containing NVP, lipid, and a surfactant which when diluted with water resulted in the formation of nanoparticles of size range varied from 70 to 1100 nm. Transmission electron microscopy and small angle neutron scattering studies of pellet and supernatant obtained after centrifugation of the IHN-DDS revealed spherical shaped nanoparticles and assembled structures, respectively. Uniform distribution of the NVP in lipid nanoparticles was confirmed by fourier transform infrared spectroscopy. Biodistribution studies in rats showed significant enhancement of NVP concentration of about 6.1, 5.8 and 3.7 fold in the liver, spleen, and brain, respectively after intravenous administration of IHN-DDS systems compared to plain NVP solution. In conclusion, IHN-DDS systems could be a promising approach for simultaneous multisite targeting and could provide therapeutic benefits in complete eradication of HIV infections.