Resveratrol-based Delivery Systems as Contemporary Nominees for Combating Pulmonary Diseases: A Comprehensive Review.

Exploiting different formulation approaches, each designed to improve the clinical use of resveratrol (RES) in treating several lung diseases. Accentuating the rationale for using RESbased delivery systems in different clinical applications in pulmonary diseases. Resveratrol (RES), a well-known natural polyphenol stilbenoid, possesses tremendous potential to treat various lung diseases owing to its anti-inflammatory, antioxidant, antiapoptotic, antiviral, and anticancer activities. Its physicochemical properties have restricted the beneficial activities of resveratrol, as it is characterized by low aqueous solubility, bioavailability and stability in addition to high photosensitivity. With the growing understanding of the effectiveness of RES in treating lung diseases, the need for attempts and advances in RES formulations should be evolved to enhance its involvement in pharmaceutical applications. This review discusses the role of RES in treating several pulmonary illnesses. For the first time, different approaches and strategies to evade its limitations and allow its clinical applications via various routes for managing a variety of respiratory ailments are presented rigorously.

Customizable resveratrol spray-dried micro-composites for inhalation as a promising contender for treatment of idiopathic pulmonary fibrosis.

The past decades have witnessed tremendous expansion in utilization of plant-derived medicines as resveratrol (RES) in treating several diseases like idiopathic pulmonary fibrosis (IPF). RES can exhibit its role in treating IPF via its outstanding antioxidant and anti-inflammatory activities. The goal of this work was to formulate RES-loaded spray-dried composite microparticles (SDCMs) suitable for pulmonary delivery via dry powder inhaler (DPI). They were prepared by spray drying of a previously prepared RES-loaded bovine serum albumin nanoparticles (BSA NPs) dispersion using different carriers. RES-loaded BSA NPs, prepared by the desolvation technique, acquired suitable particle size of 177.67 ± 0.95 nm and entrapment efficiency of 98.7 ± 0.35% with perfectly uniform size distribution and high stability. Considering the attributes of the pulmonary route, NPs were co-spray dried with compatible carriers viz. mannitol, dextran, trehalose, leucine, glycine, aspartic acid, and glutamic acid to fabricate SDCMs. All formulations showed suitable mass median aerodynamic diameter<5 µm; that is suitable for deep lung deposition. However, the best aerosolization behavior was attained from using leucine with fine particle fraction (FPF) of 75.74%, followed by glycine with FPF of 54.7%. Finally, a pharmacodynamic study was conducted on bleomycin-induced mice, and it strongly revealed the role of the optimized formulations in alleviating PF through suppressing the levels of hydroxyproline, tumor necrosis factor-α and matrix metalloproteinase-9 with obvious improvements in the treated lung histopathology. These findings indicate that in addition to leucine, the glycine amino acid, which is not commonly used yet, is very promising in the formulation of DPIs.

Travoprost Liquid Nanocrystals: An Innovative Armamentarium for Effective Glaucoma Therapy.

To date, the ophthalmic application of liquid crystalline nanostructures (LCNs) has not been thoroughly reconnoitered, yet they have been extensively used. LCNs are primarily made up of glyceryl monooleate (GMO) or phytantriol as a lipid, a stabilizing agent, and a penetration enhancer (PE). For optimization, the D-optimal design was exploited. A characterization using TEM and XRPD was conducted. Optimized LCNs were loaded with the anti-glaucoma drug Travoprost (TRAVO). Ex vivo permeation across the cornea, in vivo pharmacokinetics, and pharmacodynamic studies were performed along with ocular tolerability examinations. Optimized LCNs are constituted of GMO, Tween® 80 as a stabilizer, and either oleic acid or Captex® 8000 as PE at 25 mg each. TRAVO-LNCs, F-1-L and F-3-L, showed particle sizes of 216.20 ± 6.12 and 129.40 ± 11.73 nm, with EE% of 85.30 ± 4.29 and 82.54 ± 7.65%, respectively, revealing the highest drug permeation parameters. The bioavailability of both attained 106.1% and 322.82%, respectively, relative to the market product TRAVATAN®. They exhibited respective intraocular pressure reductions lasting for 48 and 72 h, compared to 36 h for TRAVATAN®. All LCNs exhibited no evidence of ocular injury in comparison to the control eye. The findings revealed the competence of TRAVO-tailored LCNs in glaucoma treatment and suggested the potential application of a novel platform in ocular delivery.

Assessment of antifungal efficacy of itraconazole loaded aspasomal cream: comparative clinical study.

Topical conveyance of antifungal agents like itraconazole ITZ has been giving good grounds for expecting felicitous antifungal medicines. The defiance of topical delivery of this poorly water soluble and high-molecular-weight drug, however, mightily entail an adequate vehiculation. ITZ aspasomes, newer antioxidant generation of liposomes, have been designed and enclosed in a cream to ameliorate skin deposition. The proposed creams containing non-formulated ITZ or encapsulated in aspasomes (0.1% or 0.5%) were topically applied in patients with diagnosed diaper dermatitis complicated by candidiasis, tinea corporis (TC), and tinea versicolor (TVC). Placebos (void aspasomal cream and cream base) were also utilized. The obtained results for diaper rash revealed that aspasomal cream (0.5% ITZ) was eminent with respect to complete cure and negative candida culture after 10-day therapy relative to counterparts containing 0.1% ITZ aspasomes or non-formulated ITZ (0.1% and 0.5%). For tinea, the same trend was manifested in terms of 'cleared' clinical response in 90% of patients and absence of fungal elements after 4-week treatment. Relative to non-formulated ITZ, ITZ aspasomal cream was endorsed to be auspicious especially when ITZ concentration was lowered to half commercially available cream concentration (1%), pushing further exploitation in other dermal fungal infections.

Diversifying the skin cancer-fighting worthwhile frontiers: How relevant are the itraconazole/ascorbyl palmitate nanovectors?

Fighting malignant neoplasms via repurposing existing drugs could be a welcome move for prosperous cancer remediations. In the current work, nanovehiculation and optimization of the repositioned itraconazole (ITZ) utilizing ascorbyl palmitate (AP) aspasomes would be an auspicious approach. Further, the optimized aspasomes were incorporated in a cream and tracked for skin deposition. The in vivo efficacy of aspasomal cream on mice subcutaneous Ehrlich carcinoma model was also assessed. The optimized aspasomes revealed nano size (67.83 ± 6.16 nm), negative charge (-79.40 ± 2.23 mV), > 95% ITZ entrapment and high colloidal stability. AP yielded substantial antioxidant capacity and pushed the ITZ cytotoxicity forward against A431 cells (IC50 = 5.3±0.27 µg/mL). An appealing privilege was the aspasomal cream that corroborated spreadability, contemplated skin permeation and potentiated in vivo anticancer competence, reflected in 62.68% reduction in the tumor weight. Such synergistic tumor probes set the foundation for futuristic clinical translation and commercialization.

Elaborated survey in the scope of nanocarriers engineering for boosting chemotherapy cytotoxicity: A meta-analysis study.

Cancer is the prime cause of mortality throughout the world. Although the conventional chemotherapeutic agents damage the cancerous cells, they exert prominent injury to the normal cells owing to their lack of specificity. With advances in science, many research studies have been established to boost the cytotoxic effect of the chemotherapeutic agents via innovating novel nano-formulations having different variables. In the current meta-analysis study, combined data from different research articles were gathered for the evidence-based proof of the superiority of drug loaded nanocarriers over their corresponding conventional solutions in boosting the cytotoxic effect of chemotherapy in terms of IC50 values. The meta-analysis was subdivided into three subgroups; nanoparticles versus nanofibers, surface functionalized nanocarriers versus naked ones, and protein versus non-protein-based platforms. The different subgroups interestingly showed distinct scoring outcome data paving the road for cytotoxicity enhancement of the anti-cancer drugs in an evidence-based manner.

Augmented cytotoxicity using the physical adsorption of Poloxamer 188 on allicin-loaded gelatin nanoparticles.

OBJECTIVES: The aim of this work was to study the effect of the physically adsorbed Poloxamer 188 coating polymer on the cytotoxic activity of allicin-loaded gelatin nanoparticles. METHODS: The double desolvation method was utilised to prepare the nanoparticles which were characterised for particle size (PS), polydispersity index (PDI) and zeta potential and visualised using transmission electron microscopy. The coating density of the used polymer was determined using 1H-nuclear magnetic resonance (1H-NMR); 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the cytotoxicity on HepG-2 cell lines. KEY FINDINGS: The particles were spherical possessing a PS of 714 ± 25.21 nm and a PDI of 0.663 ± 0.143. These results together with the 1H-NMR results analysis confirmed the efficient coating of Poloxamer 188. The coating of particles rendered them more cytotoxic, scoring an IC50 of 6.736 µm (2-folds lower than the uncoated counter parts and 4-folds lesser than the allicin solution), and apt for cancer-targeting. Moreover, the prepared nanoparticles were stable to gamma-sterilisation and to a storage of 12 months. CONCLUSIONS: Augmented cytotoxicity on HepG-2 cell lines was obtained using the physical adsorption of an abundant and relatively cheap material, Poloxamer 188, on allicin-loaded gelatin nanoparticles.

Delineating penetration enhancer-enriched liquid crystalline nanostructures as novel platforms for improved ophthalmic delivery.

Liquid crystalline nanostructures (LCNs), for instance cubosomes, have been widely used as a promising carrier for drug delivery through the last few years. To date, the ophthalmic application of these platforms was not well explored, and the effect of integrating penetration enhancers (PEs) into LCNs has not been investigated yet. Hence, the present work aimed coupling novel PEs into glyceryl monooleate-based cubosomes for ocular administration. Various enhancers viz, free fatty acids (oleic and linoleic acids), natural terpenes (D-limonene and cineole), medium-chain triglycerides (Captex® 1000 and Captex® 8000), mono-/di-glycerides (Capmul® MCM, Capmul® PG-8, and Capmul® PG-12) were tested at different amounts. The morphology of the formed LCNs was investigated using transmission electron microscopy (TEM). The crystallinity and thermal behavior studies were also conducted. The ocular safety of optimized formulae was tested via hen's egg test-chorioallantoic membrane (HET-CAM), rabbit eye Draize test, and histopathological examinations of ocular tissues. Confocal laser scanning microscopy (CLSM) was utilized to assess the enhanced permeation of fluorescently-labeled LCNs across corneal layers. The acceptable formulations exhibited relatively homogenous particle nano-sizes ranging from 139.26 ± 3.68 to 590.56 ± 24.86 nm carrying negative surface charges. TEM images, X-ray patterns and DSC thermograms demonstrated the influential effect of PEs in developing altered crystalline structures. The ocular compatibility of optimized LCNs was confirmed. The corneal distribution using CLSM proved the disseminated fluorescence intensity of LCNs enriched with oleic acid, Captex® 8000 and Capmul® MCM. Selected LCNs showed good physical stability upon storage and lyophilization. The results demonstrated the efficiency of tailored PE-modified LCNs in enhancing the ocular transport with no evidence of any irritation potential, and hence suggested their prospective applicability in ophthalmic drug delivery.

Enhanced Allicin Cytotoxicity on HEPG-2 Cells Using Glycyrrhetinic Acid Surface-Decorated Gelatin Nanoparticles.

The cytotoxic potential of allicin was evaluated on different cancer cell lines, particularly, hepatic (HepG-2), breast (MCF-7), lung (A-549), and prostatic (PC-3), where allicin scored an IC50 score of 19.26 µM on HepG-2. In order to increase the cell uptake, optimized allicin-loaded gelatin nanoparticles (GNPs) were prepared where the optimum formulation was surface-conjugated to glycyrrhetinic acid. GNPs were optimized using a D-optimal design. The optimum formulation had a particle size of 370.7 ± 6.78 nm and polydispersity index of 0.0363 ± 0.009 and 39.13 ± 2.38% of drug entrapment. The conjugation of the ligand, glycyrrhetinic acid with allicin-loaded GNPs, was confirmed utilizing 1H NMR. Drug release profiles in the presence/absence of collagenase were obtained. Finally, a cytotoxicity study on HepG-2 was performed for the unconjugated and conjugated allicin-loaded GNPs scoring IC50 of 10.95 and 5.046 µM, revealing two- and fourfold enhancements in allicin cytotoxicity, respectively. To our knowledge, the ligand-carrier pair, glycyrrhetinic acid-gelatin, was not explored before, and the developed system poses a successful liver cancer therapy.

Exploiting gelatin nanocarriers in the pulmonary delivery of methotrexate for lung cancer therapy.

Gelatin has many merits that encourage its use in the pulmonary delivery of anticancer drugs. It is a biodegradable denatured protein which possesses several functional groups that could be modified. Additionally, it has balanced hydrophilic and hydrophobic characters, which facilitate the loading of chemotherapeutic agents. Accordingly, the purpose of the current work was to exploit this valuable biomaterial in the efficient pulmonary delivery of methotrexate in case of lung cancer. Gelatin nanoparticles were prepared via a desolvation method and the fabrication process was optimized using Box Behnken design of experiment. A comparative study on uptake of gelatin nanoparticles by lung adenocarcinoma cells and macrophages was implemented using flow cytometry. Investigation of the effect of different methotrexate loading techniques: encapsulation, post loading and chemical conjugation on the nanoparticles characteristics and cellular cytotoxicity was performed. Nano-in-microparticles were prepared by co-spray drying optimized nanoparticles with leucine. Results showed that Box Behnken design was able to optimize preparation parameters to yield uniform nanoparticles with suitable particle size for cancer cells uptake. The prepared nanoparticles demonstrated a preferential uptake by lung cancer cells. Additionally, methotrexate loaded nanoparticles demonstrated up to four fold significant reduction in methotrexate IC50. The spray dried gelatin nano-in microparticles demonstrated good aerosolization properties enabling lung deposition in the respirable airways. Thus, providing a promising platform for lung cancer therapy.

Polysaccharides-based nanocomplexes for the prolonged delivery of enoxaparin: In-vitro and in-vivo evaluation.

Thromboprophylaxis and anticoagulant therapy face serious medical challenges in terms of how crucial it is to maintain therapeutic activity of the anticoagulant agent over the required period of time. Failure to do so will lead to an increased risk of clot propagation if a subtherapeutic drug level is reached. On the other hand, higher-than intended anticoagulation levels might lead to an enhanced risk of hemorrhagic complications. Nanocomplexes (NCs) for the controlled delivery of the antithrombotic Enoxaparin (Enox) with dextran sulfate (DS) and chitosan (CS) were formulated, in an attempt to circumvent therapeutic and compliance challenges associated with the prolonged administration of the current dosage form. Using polyelectrolyte complexation method, various fabrication and formulation parameters were tested. Assessment of ex-vivo stability of selected formulae in rat serum was done prior to determination of their pharmacokinetic profile. High EE% was achieved in all systems prepared. In absence of DS, target size was obtained when 0.54mg/mL CS at an initial pH of 5 and Enox to CS mass ratio of 1:2.5 were employed at room temperature. These parameters were shifted to new optima upon introduction of DS. The anticoagulant activity of NCs (in absence/presence of DS) was significantly sustained compared to the market product (135 and >144h versus 5h, respectively).

Anti-tumor efficacy of an integrated methyl dihydrojasmonate transdermal microemulsion system targeting breast cancer cells: In vitro and in vivo studies.

Targeting solid tumors transdermally is an emerging approach that is currently under intense investigation. In this context, microemulsions are reported as one of the most favored carriers for successful transdermal drug delivery. Thereby, these nano-carriers were utilized in this study for the delivery of a phytochemical, namely methyl dihydrojasmonate (MDHJ), which has previously demonstrated an anticancer effect. Accordingly, pseudoternary phase diagrams were constructed using several combinations of oils, surfactants and co-surfactants and following the water titration method. Two systems were selected and an experimental design (Simplex Lattice Mixture Design) was utilized to select formulations for further investigation through an ex vivo permeation study through mouse skin. Transdermal fluxes were determined reaching a value of 0.07µlcm-2h-1. Cytotoxicity studies were carried out where the selected superlative formulation was further investigated on MCF-7 cell lines and scored an IC50 of 42.2µl/ml (equivalent to 8.3µl/ml drug). Further, in vivo investigations were performed using Ehlirch solid carcinoma and histopathological examination of the tumor cells evaluating the tumor volume differences, tumor inhibition percentages and the necrotic effect of the formulation compared to control, placebo and pure drug. The obtained results showed significant anticancer effects of the selected formulation when applied on the tumor bearing mice skin.

A novel serum-stable liver targeted cytotoxic system using valerate-conjugated chitosan nanoparticles surface decorated with glycyrrhizin.

The aim of this study was to target a naturally chemotherapeutic agent: ferulic acid to the liver using a biocompatible and an in vivo stable carrier. Accordingly, chitosan as a biopolymer was modified using a hydrophobic moiety and valeric acid in order to increase its in vivo stability. The structure of the newly synthesized product was confirmed using FT-IR and NMR techniques together with the ninhydrin assay. Ferulic acid was conjugated to the modified nanoparticles that were further characterized for particle size, PDI and zeta potential and subjected to ex vivo stability study in serum and cytotoxicity studies in HepG2 cell lines. Furthermore, the nanoparticles were surface-decorated with glycyrrhizin for active liver targeting. The in vivo biodistribution was experimented using radiolabeling assay where the liver scored the highest accumulation of the glycyrrhizin containing nanoparticles after 6h reaching a value of 13.34%ID/g of the total injected dose of labeled drug compared to drug solution and glycyrrhizin free nanoparticles where the accumulation percent did not exceed 4.19%ID/g and 4.26%ID/g, respectively. As a conclusion, the conducted physico-chemical and biological investigations suggested that the proposed selected system can be efficiently utilized as a successful platform for targeting a natural chemotherapeutic agent viz. ferulic acid to the liver.

Statins anticancer targeted delivery systems: re-purposing an old molecule.

OBJECTIVES: Exploring the use of statins as anticancer agents and exploiting different drug delivery systems in targeting these molecules to cancerous sites. Literature review was performed to investigate the use of statins in cancer treatment in one hand, and the different pharmaceutical approaches to deliver and target these drugs to their site of action. KEY FINDINGS: Statins were used for decades as antihypercholestrolemic drugs but recently have been proven potential for broad anticancer activities. The incorporation of statins in nanoparticulate drug delivery systems not only augmented the cytotoxicity of statins but also overcame the resistance of cancerous cells against the traditional chemotherapeutic agents. Statins-loaded nanoparticles could be easily tampered to target the cancerous cells and consequently minimal drug amount could be utilized. SUMMARY: This review reconnoitered the different endeavors to incorporate statins in various nanoparticles and summarized the successful effects in targeting cancerous cells and reducing their proliferation without the side effects of commonly used chemotherapeutic agents.

Nanostructured lipid carriers loaded with simvastatin: effect of PEG/glycerides on characterization, stability, cellular uptake efficiency and in vitro cytotoxicity.

OBJECTIVE: The aim of this study is to evaluate the use of PEG/glycerides of different HLB; oleoyl macrogol-6-glycerides (Labrafil® M 1944 CS) and caprylocaproylmacrogol-8-glycerides (Labrasol®), compared to Labrafac lipophile® as PEG-free glyceride in the preparation of nanostructured lipid carriers (NLCs). PEG/glycerides are suggested to perform a dual function; as the oily component, and as the PEG-containing substrate required for producing the PEGylated carriers without physical or chemical synthesis. METHODS: Lipid nanocarriers were loaded with simvastatin (SV) as a promising anticancer drug. An optimization study of NLC fabrication variables was first conducted. The effect of lyophilization was investigated using cryoprotectants of various types and concentrations. The prepared NLCs were characterized in terms of particle size (PS), size distribution (PDI), zeta potential (ZP), drug entrapment, in vitro drug release, morphology and drug-excipient interactions. The influence of glycerides ± PEG on the cytotoxicity of SV was evaluated on MCF-7 breast cancer cells, in addition to the cellular uptake of fluorescent blank NLCs. RESULTS: The alteration between different oil types had a significant impact on PS, ZP and drug release. Both sucrose and trehalose showed the lowest increase in PS and PDI of the reconstituted lyophilized NLCs. The in vitro cytotoxicity and cellular uptake studies indicated that SV showed the highest antitumor effect on MCF-7 cancer cells when loaded into Labrasol® NLCs demonstrating a high cellular uptake as well. CONCLUSION: The study confirms the applicability of PEG/glycerides in the development of NLCs. Encapsulating SV in Labrasol®-containing NLC could enhance the antitumor effect of the drug.

Passive targeting and lung tolerability of enoxaparin microspheres for a sustained antithrombotic activity in rats.

Pulmonary bed can retain microparticles (MP) larger than their capillaries' diameter, hence we offer a promising way for lung passive targeting following intravenous (IV) administration. In this study, enoxaparin (Enox)-albumin microspheres (Enox-Alb MS) were, optimally, developed as lung targeted sustained release MP for IV use. Lung tolerability and targeting efficiency of Enox-Alb MS were tested, and the pharmacokinetic profile following IV administration to albino rats was constructed. In vivo studies confirmed high lung targeting efficiency of Enox-Alb MS with lack of potential tissue toxicity. The anticoagulant activity of the selected Alb MS was significantly sustained for up to 38 h compared to 5 h for the market product. Alb MS are promising delivery carriers for controlled and targeted delivery of Enox to the lungs for prophylaxis and treatment of pulmonary embolism.

Augmented simvastatin cytotoxicity using optimized lipid nanocapsules: a potential for breast cancer treatment.

CONTEXT: We noticed paucity in exploiting solutol-based lipid nanocapsules in statins formulations though they carry all favorable properties that are needed for cancer passive targeting such as their small particle size, stealth properties, ability to highly accommodate lipophilic drugs, good internalization and P-gp pump inhibition. OBJECTIVE: The aim of this study was to design and optimize new simvastatin drug delivery systems; lipid nanocapsules intended for administration through the intravenous route as potential treatment for breast cancer. METHODS: Optimized nanocapsules were prepared by the phase-inversion method according to a D-optimal mixture design, characterized and assessed for their cytotoxicity. RESULTS: Three successful models for particle size, polydispersity index (PDI) and percentage of drug released after 48 h were generated. The prepared lipid nanocapsules acquired spherical and homogenous morphology, good stability and tolerance to sterilization. The obtained release profiles demonstrated desired sustained release pattern. Furthermore, testing selected formulations on human breast cancer adenocarcinoma cells showed augmented cytotoxicity of simvastatin reaching low IC50 values as 1.4 ± 0.02 µg/ml compared to the pure drug. CONCLUSION: The proposed lipid nanocapsules pose promising candidates as simvastatin carriers intended for the targeting of breast cancer.

Synthesis and evaluation of alendronate-modified gelatin biopolymer as a novel osteotropic nanocarrier for gene therapy.

AIM: To synthesize an osteotropic alendronate functionalized gelatin (ALN-gelatin) biopolymer for nanoparticle preparation and targeted delivery of DNA to osteoblasts for gene therapy applications. MATERIALS & METHODS: Alendronate coupling to gelatin was confirmed using Fourier transform IR, (31)PNMR, x-ray diffraction (XRD) and differential scanning calorimetry. ALN-gelatin biopolymers prepared at various alendronate/gelatin ratios were utilized to prepare nanoparticles and were optimized in combination with DNA and gemini surfactant for transfecting both HEK-293 and MG-63 cell lines. RESULTS: Gelatin functionalization was confirmed using the above methods. Uniform nanoparticles were obtained from a nanoprecipitation technique. ALN-gelatin/gemini/DNA complexes exhibited higher transfection efficiency in MG-63 osteosarcoma cell line compared with the positive control. CONCLUSION: ALN-gelatin is a promising biopolymer for bone targeting of either small molecules or gene therapy applications.

Low molecular weight heparins for current and future uses: approaches for micro- and nano-particulate delivery.

Low molecular weight heparins (LMWHs), the anticoagulant drug of choice in many indications, had been suggested as novel drug treatment for a range of diseases. Their superior pharmacokinetic properties compared to unfractionated heparin (UFH), motivated scientists to explore new delivery systems for improved therapeutic outcomes. Micro- and nano-carriers, with the versatile nature and characteristics of materials used for their fabrication, are able to surmount the challenges opposed by their native structures. The present review discusses the recent perspectives on the development of micro- and nano-particulate vectors for the delivery of LMWHs through various routes. Special focus on the application of the suggested systems, their characterization and the achieved improved bioavailability will be given throughout the review.

Impact of microparticle formulation approaches on drug burst release: a level A IVIVC.

AIM: To study the effect of poly(d,l-lactic-co-glycolic acid) (PLGA) microparticles (MPs) preparation techniques on particle physical characterization with special emphasis on burst drug release. METHODS: A basic drug clozapine was used in combination with acid-terminated PLGA. Two approaches for MP preparation were compared; the in situ forming microparticle (ISM) and the emulsion-solvent evaporation (ESE) methods using an experimental design. The MPs obtained were compared according to their physical characterization, burst release and T80%. An in vivo pharmacokinetic study with in vitro-in vivo correlation (IVIVC) was also performed for the selected formula. RESULTS: Both methods were able to sustain drug release for three weeks. ISM produced more porous particles and was not effective as ESE for controlling burst release. A good IVIVC (R(2) = 0.9755) was attained when injecting the selected formula into rats. CONCLUSION: MPs prepared with ESE showed a minimum burst release and a level A IVIVC was obtained when administered to rats.