The Antibacterial Effect of Ciprofloxacin Loaded Calcium Carbonate (CaCO3) Nanoparticles Against the Common Bacterial Agents of Osteomyelitis.

The present study aimed to investigate the biocompatibility, antibacterial/anti-biofilm effects of ciprofloxacin-loaded calcium carbonate (Cip- loaded CaCO3) nanoparticles against the common organisms responsible for osteomyelitis. The antibacterial and biofilm inhibitory activities were studied by determination of minimum inhibitory concentrations (MICs) and minimum biofilm inhibitory concentrations (MBICs), respectively. Hemolytic effects were determined for studying hemocompatibility. The SDS-PAGE method was used to study the interaction of Cip- loaded CaCO3 with plasma proteins. The effects of Cip- loaded CaCO3 on the cell viability of human bone marrow mesenchymal stem cells (hBM-MSCs) was detected. The Cip- loaded CaCO3 nanoparticles were shown a significant antimicrobial effect at lower concentrations than free ciprofloxacin. No significant hemolytic effect was observed. The Cip- loaded CaCO3 nanoparticles have shown interaction with apolipoprotein A1 (28 kDa) and albumin (66.5 kDa). The viability of hBM-MSCs treated with Cip- loaded CaCO3 was more than 96%. Our results indicated that Cip-loaded CaCO3 nanoparticles had favorable in vitro compatibility with human red blood cells, antimicrobial effects, and low cytotoxicity.

Advances in Aptamers-Based Applications in Breast Cancer: Drug Delivery, Therapeutics, and Diagnostics.

Aptamers are synthetic single-stranded oligonucleotides (such as RNA and DNA) evolved in vitro using Systematic Evolution of Ligands through Exponential enrichment (SELEX) techniques. Aptamers are evolved to have high affinity and specificity to targets; hence, they have a great potential for use in therapeutics as delivery agents and/or in treatment strategies. Aptamers can be chemically synthesized and modified in a cost-effective manner and are easy to hybridize to a variety of nano-particles and other agents which has paved a way for targeted therapy and diagnostics applications such as in breast tumors. In this review, we systematically explain different aptamer adoption approaches to therapeutic or diagnostic uses when addressing breast tumors. We summarize the current therapeutic techniques to address breast tumors including aptamer-base approaches. We discuss the next aptamer-based therapeutic and diagnostic approaches targeting breast tumors. Finally, we provide a perspective on the future of aptamer-based sensors for breast therapeutics and diagnostics. In this section, the therapeutic applications of aptamers will be discussed for the targeting therapy of breast cancer.

Targeted combined therapy in 2D and 3D cultured MCF-7 cells using metformin and erlotinib-loaded mesoporous silica magnetic nanoparticles.

AIM: This research aims to develop potential therapeutic nanostructures (NSs) encapsulating metformin (MET) and erlotinib (ER) for combinational therapy in breast cancer. METHODS: The ER and MET, both were loaded on mesoporous silica magnetic nanoparticles conjugated with polyethylene glycol and methotrexate to achieve targeted NSs. The developed NSs were characterised using SEM, DLS, and FTIR. Afterward, MTT, Trypan blue, and DNA extraction assays were operated for biological evaluations in the 2D and 3D MCF-7 cells. RESULTS: Physicochemical approaches indicated the mean diameter of 69.4 nm ± 9.5 (PDI = 0.64), and neutral charge (2 mv) for the developed NSs. MET and ER-loaded NSs exhibited 62.56% ± 4.41 and 67.73% ± 3.03 drug release amount in pH = 5.4, respectively. MTT assay revealed that ER- and MET-loaded NSs had less metabolic activity (≈ 20%) in comparison with non-targeted NSs. CONCLUSION: Overall, our combined ER and MET-loaded targeted NSs result in a synergistic inhibitory impact on MCF-7 cells.

Solubility of codeine phosphate in carbitol + 2-propanol mixture at different temperatures.

The solubility profile of codeine phosphate in the carbitol and 2-propanol mixtures at 293.2-313.2 K are determined and correlated with some developed cosolvency models. Moreover, the density values of codeine phosphate saturated solutions are also determined and fitted with the Jouyban-Acree model. The model accuracy is investigated by calculating the mean relative deviations (MRDs%). The thermodynamic parameters of codeine phosphate dissolution in the non-aqueous mixtures of carbitol and 2-propanol are also computed by using van't Hoff and Gibbs equations.

Piroxicam cocrystals with phenolic coformers: preparation, characterization, and dissolution properties.

This study explores the preparation and investigation of dissolution properties of piroxicam cocrystals. Differential scanning calorimetry (DSC) was used to determine the capability of resorcinol (RES), methylparaben (MPB), and vanillin (VAN) to form cocrystals with piroxicam (PRX). Generation of cocrystals was attempted by liquid assisted grinding and slurry methods. Cocrystals were characterized by thermal methods, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. Apparent solubility, intrinsic dissolution rate (IDR), and powder dissolution profile of cocrystals were compared with anhydrous piroxicam, piroxicam monohydrate (PRXMH), and previously reported piroxicam-succinic acid cocrystal. Contact angles and particle sizes of the studied solids were also measured. Based on the DSC screening results, we prepared and characterized PRX-RES and PRX-MPB cocrystals. Interestingly, the cocrystals not only failed to improve apparent solubility and IDR of PRX but also showed lower values than PRX that were attributed to induction of phase transformation of PRX to PRXMH. In contrary, cocrystals performed better than PRX in powder dissolution studies. The higher dissolution rates of cocrystals were explained by improved wettability and reduced sizes. This study has highlighted the complexity of solid state properties of cocrystals and has provided new evidence for the in-solution stability issues of cocrystals.

Feasibility of electrospray deposition for rapid screening of the cocrystal formation and single step, continuous production of pharmaceutical nanococrystals.

OBJECTIVES: This study employed electrospray deposition (ESD) for simultaneous synthesis and particle engineering of cocrystals. SIGNIFICANCE: Exploring new methods for the efficient production of cocrystals with desired particle properties is an essential demand. METHODS: The possibility of cocrystal formation by ESD was examined for indomethacin-saccharin, indomethacin-nicotinamide, naproxen-nicotinamide, and naproxen-iso-nicotinamide cocrystals. Solutions of the drug and coformer at stoichiometric ratios were sprayed to a high electric field which caused rapid evaporation of the solvent and the formation of fine particles. The phase purity, size, and morphology of products were compared with reference cocrystals. Experiments were performed to evaluate the effects of stoichiometric ratio, concentration and solvent type on the cocrystal formation. Physical stability and dissolution properties of the electrosprayed cocrystals were also compared with reference cocrystals. RESULTS: ESD was found to be an efficient and rapid method to produce cocrystals for all studied systems other than indomethacin-nicotinamide. Pure cocrystals only formed at a specific drug:coformer ratio. The solvent type has a weak effect on the cocrystal formation and morphology. Electrosprayed cocrystals exhibited nano to micrometer sizes with distinct morphologies with comparable physical stability with reference cocrystals. Nanococrystals of indomethacin-saccharin with a mean size of 219 nm displayed a threefold higher dissolution rate than solvent evaporated cocrystal. CONCLUSION: ESD successfully was utilized to produce pure cocrystals of poorly soluble drugs with different morphologies and sizes ranging from nano to micrometer sizes in one step. This study highlighted the usefulness of ESD for simultaneous preparation and particle engineering of pharmaceutical cocrystals.

Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability.

BACKGROUND: We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. METHODS: Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. RESULTS: The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. CONCLUSION: This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

How do lipid-based drug delivery systems affect the pharmacokinetic and tissue distribution of amiodarone? A comparative study of liposomes, solid lipid nanoparticles, and nanoemulsions.

Objectives: Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading to off-target accumulation and toxicity. Amiodarone as an anti-arrhythmic agent induces hypothyroidism and liver disorders limiting its clinical indication. Materials and Methods: In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized. Results: The nanoparticles were spherical with a diameter of 100-200 nm and sustained in vitro drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. In vivo studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (Cmax) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (P-value<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes. Conclusion: Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.

Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-ß (IL1-ß) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

Solubility of mesalazine in pseudo-binary mixtures of choline chloride/ethylene glycol deep eutectic solvent and water at 293.15 K to 313.15 K.

Mesalazine (5-ASA) is a medication utilized to treat inflammatory bowel diseases involving ulcerative colitis and Crohn's disease. Mesalazine has fewer side effects but the low solubility and bioavailability of it is responsible for its delayed onset of action. Hence, the goal of this study is to determine the molar solubility of 5-ASA in aqueous pseudo-binary mixtures containing low toxic biocompatible choline chloride/ethylene glycol deep eutectic solvent (ChCl/EG DES) with DES mass fraction of 0.0-1.0 using a shake-flask technique at 293.2-313.2 K and approximately 85 kPa. The experimental results indicated that the solubility of 5-ASA enhanced by addition of DES mass fraction and also increasing temperature. The molarity values of 5-ASA were then modelled by some traditional cosolvency models, and regressed each model parameters. The back-computed molarity of 5-ASA using the selected cosolvency models presented a good consistency with the experimental data (lower mean percentage deviation than 5.14%). Moreover, the Gibbs and van't Hoff equations were employed to compute the thermodynamic functions of 5-ASA dissolution process in ChCl/EG DES + water from the temperature dependency of solubility data. This analysis presented an endothermic and entropy-driven process of 5-ASA dissolution in ChCl/EG DES + water. Furthermore, enthalpy-entropy compensation analysis represented non-linear enthalpy dissolution vs. Gibbs free energy compensation plots with positive and negative slopes for 5-ASA whereas the positive and negative slopes were probably due to the enhance in solvation of 5-ASA by ChCl/EG DES molecules and the solvent-structure loosing, respectively.

A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption.

PURPOSE: Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. METHODS: A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. RESULTS: The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. CONCLUSION: The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption.

Changing the daily injection of glatiramer acetate to a monthly long acting product through designing polyester-based polymeric microspheres.

Introduction: Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation. Methods: Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed. Results: The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release. Conclusion: Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered.

Nanomaterials and Stem Cell Differentiation Potential: An Overview of Biological Aspects and Biomedical Efficacy.

Nanoparticles (NPs), due to their medical applications, are widely used. Accordingly, the use of mesenchymal stem cells is one of the most important alternatives in the tissue engineering field. NPs play effective roles in stem cells proliferation and differentiation. The combination of NPs and tissue regeneration by stem cells has created a new therapeutic approach towards humanity. Of note, the physicochemical properties of NPs determine their biological function. Interestingly, various mechanisms such as modulation of signaling pathways and generation of reactive oxygen species, are involved in NPs-induced cellular proliferation and differentiation. This review summarized the types of nanomaterials effective on stem cell differentiation, the physicochemical features, biomedical application of these materials and the relationship between nanomaterials and environment.

Development of amitriptyline buccoadhesive tablets for management of pain in dental procedures.

Administration of lidocaine and nonsteroidal anti-inflammatory drugs (NSAIDs) as a routine procedure for relief of dental pains by and large is restricted due to some side effects. Amitriptyline (AM) has long been known to exert analgesic activity as a result of blocking the Na⁺ channels. The objective of the present investigation was to prepare suitable buccoadhesive tablets using cellulose derivatives in order to obtain new formulations containing AM to provide local analgesic action. The tablets were evaluated in terms of physical characteristics, mucoadhesion performance, drug release, and in vivo assessment of analgesic efficiency. Tablets containing higher amounts of high-viscosity hydroxypropylmethyl cellulose (HPMC-K4M) significantly demonstrated enhanced adhesive performances. On the other hand, presence of sodium carboxymethyl cellulose (NaCMC) in formulations including HPMC of lower-viscosity grade (HPMC-E5LV) provided further adhesiveness by increase in viscosity. Rate of drug release from HPMC-E5LV tablets was significantly higher than the HPMC-K4M tablets. Kinetically, patterns of AM release from the tablets fitted best to Higuchi model. Moreover, in a randomized double-blind trial, analgesic efficiency of the prepared bioadhesive tablets was revealed to be satisfactory. It is suggested that applying the topical AM mucoadhesive tablet containing the low amount of drug is a safe and promising alternative to relief the pain in the buccal region.

Osteogenesis Promotion of Selenium-Doped Hydroxyapatite for Application as Bone Scaffold.

The combined bioceramic of selenium (Se) and hydroxyapatite (HA) has been considered as a moderate bone scaffold biomaterial. In the present work, Se was doped into the HA structure using the mechano-chemical alloying (MCA) method for the improvement of osteogenic properties of HA. HA extracted from fish bone and Se-doped hydroxyapatite (Se-HA) were analyzed using X-ray diffraction spectra (XRD), scanning electron microscope (SEM), energy dispersion X-ray spectrometer (EDX), and Fourier transform infrared spectroscopy (FT-IR). In-vitro cell responses on the Se-HA bioceramic scaffold were investigated using human adipose-derived mesenchymal stem cells (hAD-MSCs). The effect of Se on cell proliferation was studied by MTT assay, and cell adhesion responses were analyzed by optical microscopy and SEM. Furthermore, the effect of Se on osteogenic properties of HA was studied by alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and Western blot tests. The MTT results showed that the Se dopant synergistically increases the proliferation of hAD-MSCs. Moreover, good cell-adhesive and osteoblast-shaped behaviors were observed on the Se-HA scaffold. The results of osteogenic differentiation demonstrated synergistically enhanced ALP activity and calcification on the Se dopant compared to HA. Also, the results of Western blot test presented that the differentiation of hAD-MSCs toward being a bone tissue was increased by up to 50% while selenium doping. Additional MTT analysis using Human Bone Osteosarcoma cell line (KHOS-240S) revealed the antiproliferative activity of the Se-HA scaffold against bone cancerous cells. Therefore, it has been concluded that Se-HA bioceramic can be employed as a scaffold with simultaneous anticancer and bone regenerative properties.

Silver nanoparticles induce the cardiomyogenic differentiation of bone marrow derived mesenchymal stem cells via telomere length extension.

Finding new strategies for the treatment of heart failures using stem cells has attracted a lot of attention. Meanwhile, nanotechnology-based approaches to regenerative medicine hypothesize a possible combination of stem cells and nanotechnology in the treatment of diseases. This study aims to investigate the in vitro effect of silver nanoparticles (Ag-NPs) on the cardiomyogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through detection of cardiac markers. For this purpose, MSCs were isolated from bone marrow resident and differentiated to the cardiac cells using a dedicated medium with Ag-NPs. Also, the cardiomyogenic differentiation of BM-MSCs was confirmed using immunocytochemistry. Then, real-time PCR and western blotting assay were used for measuring absolute telomere length (TL) measurement, and gene and protein assessment of the cells, respectively. It was found that 2.5 µg/mL Ag-NPs caused elongation of the telomeres and altered VEGF, C-TnI, VWF, SMA, GATA-4, TERT, and cyclin D protein and gene expression in the cardiomyogenically differentiated BM-MSCs. Also, there was a significant increase in the protein and gene expression of Wnt3 and ß-catenin as main components of pathways. We concluded that Ag-NPs could change the in vitro expression of cardiac markers of BM-MSCs via the Wnt3/ß-catenin signaling pathway.

Folate receptor-mediated delivery of 1-MDT-loaded mesoporous silica magnetic nanoparticles to target breast cancer cells.

Aims: The efficiency of mesoporous silica magnetic nanoparticles (MSMNP) as a targeted drug-delivery system was investigated. Methods: The superparamagnetic iron oxide nanoparticles (NP) were synthesized, coated with mesoporous silica and conjugated with polyethylene glycol and methotrexate. Next, 1-methyl-D-tryptophan was loaded into the prepared nanosystems (NS). They were characterized using transmission electron microscopy, scanning electron microscopy, dynamic light scattering, vibrating sample magnetometer, x-ray powder diffraction, Fourier transform-infrared spectroscopy and the Brunauer-Emmett-Teller method and their biological impacts on breast cancer cells were evaluated. Results: The prepared NSs displayed suitable properties and showed enhanced internalization by folate-receptor-expressing cells, exerting efficient cytotoxicity, which was further enhanced by the near-infrared radiation irradiation. Conclusion: On the basis of our findings, the engineered NS is a promising multifunctional nanomedicine/theranostic for solid tumors.

Recent advances in breast cancer immunotherapy: The promising impact of nanomedicines.

Breast cancer (BC) is one of the prevalent cancers among women. Generally, the treatment of BC is mostly based on several prominent strategies, including chemotherapy, surgery, endocrine therapy, molecular targeted therapy, and radiation. Owing to the growing knowledge about the complexity of BC pathobiology, immunotherapy as a promising treatment modality has substantially improved the patients' care in the clinic. Immunotherapy is used to harness the patient's immune system to recognize and battle devious cancer cells. As a novel therapy approach, this emerging strategy targets the key molecular entities of tumor tissue. To achieve maximal therapeutic impacts, the dynamic interplay between cancer and immune cells needs to be fully comprehended. The key molecular machinery of solid tumors can be targeted by nanoscale immunomedicines. While discussing the potential biomarkers involved in the initiation and progression of BC, we aimed to provide comprehensive insights into the immunotherapy and articulate the recent advances in terms of the therapeutic strategies used to control this disease, including immune checkpoint inhibitors, vaccines, chimeric antigen receptor T cells therapy, and nanomedicines.

Stimuli-responsive graphene oxide and methotrexate-loaded magnetic nanoparticles for breast cancer-targeted therapy.

Aim: Nanocomposites of graphene oxide (GO) loaded with PEGylated superparamagnetic iron oxide nanoparticles and grafted with methotrexate and stimuli-responsive linkers (GO-SPION-MTX) were developed for photothermal and chemotherapy of breast cancer. Methods: PEGylated SPIONs were synthesized and conjugated with chemotherapeutic targeting agent MTX, which were then loaded on GO to prepare GO-SPION-MTX nanocomposites. To evaluate the photothermal effect of the nanocomposites, they were examined in breast cancer cell lines with low doses of near-infrared (NIR) laser radiation with/without acetazolamide. Results: The GO-SPION-MTX nanocomposites were found to be internalized by the folate-receptor-positive cancer cells and induce high cytotoxicity on exposure to NIR laser rays. Conclusion: Our findings suggest that the GO-SPION-MTX nanocomposite can potentially be used as a multimodal nanomedicine/theranostic against breast cancer.

A quantitative approach to predicting lung deposition profiles of pharmaceutical powder aerosols.

Dry powder inhalers (DPI) are widely used systems for pulmonary delivery of therapeutics. The inhalation performance of DPIs is influenced by formulation features, inhaler device and inhalation pattern. The current review presents the affecting factors with great focus on powder characteristics which include particle size, shape, surface, density, hygroscopicity and crystallinity. The properties of a formulation are greatly influenced by a number of physicochemical factors of drug and added excipients. Since available particle engineering techniques result in particles with a set of modifications, it is difficult to distinguish the effect of an individual feature on powder deposition behavior. This necessitates developing a predictive model capable of describing all influential factors on dry powder inhaler delivery. Therefore, in the current study, a model was constructed to correlate the inhaler device properties, inhalation flow rate, particle characteristics and drug/excipient physicochemical properties with the resultant fine particle fraction. The r2 value of established correlation was 0.74 indicating 86% variability in FPF values is explained by the model with the mean absolute errors of 0.22 for the predicted values. The authors believe that this model is capable of predicting the lung deposition pattern of a formulation with an acceptable precision when the type of inhaler device, inhalation flow rate, physicochemical behavior of active and inactive ingredients and the particle characteristics of DPI formulations are considered.