Development and evaluation of febuxostat solid dispersion through screening method

Febuxostat (Febux) is a BCS II drug and has a very low solubility. In order to overcome this shortcoming, the purpose of study is to increase the in vitro dissolution (%) and drug release (%) of Febux by using a screening method. The Febux-SD formulation was prepared by screening solubilizers, pH agents, and carriers using with a solvent evaporation method.The novel Febux SD formulation was successfully developed. The dissolution (%) of Febux of optimal formulation (SD3) was higher than that of Feburic® tab in pH 1.2, distilled water (DW), and pH 6.8 buffer by 6.3-, 2.6-, and 1.1-fold, respectively, at 60 min. The in vitro drug release (%) and permeability (μg/cm²) of SD3 formulation were improved compared to those of Feburic® tab in the pH shifting method and PBS (7.4), respectively. The SD3 formulation was well maintained the stability for 6 months, and that of physicochemical properties were altered. In conclusion, the Febux solubilization study with meglumine was first attempted and successfully performed. Through the improved dissolution (%) of Febux, high bioavailability of SD3 formulation is expected in animal and human studies.     

Investigating a Modified Apparatus to Discriminate the Dissolution Capacity In Vitro and Establish an IVIVC of Mycophenolate Mofetil Tablets in the Fed State

In this study, a modified dissolution apparatus was developed by equipping a USP apparatus Ⅰ with an open-loop system to discriminate the dissolution capacity in vitro and establish an in vitro and in vivo correlation (IVIVC) for mycophenolate mofetil (MMF) tablets. MMF had strong pH-dependent solubility that could influence the dissolution rate in vivo after the meal. Dissolution tests involving reference (Cellcept®) and test formulations (F1 and F2) were conducted using pH 4.5 acetate buffer to simulate gastric fluids in the fed state. The dissolution profiles of the reference and test formulations were distinguished by using the modified dissolution apparatus and compared with those determined using the USP apparatuses Ⅱ and Ⅳ, and the dissolution capacities of the formulations were discriminated at different sampling time-points. The results of human bioequivalence (BE) studies in the fed state were consistent with in vitro evaluations that the maximum concentrations (C_{max, in vivo}) of both F1 and F2 fell below the acceptable range (80.00%). A level A IVIVC between the absorption fraction in vivo and dissolution in vitro, and a level C correlation between C_{max, in vivo} and C_{max, in vitro}, were established to guide the optimization of the tablet formulation containing MMF.     

Simultaneous Analysis of Dissolution and Permeation Profiles of Nanosized and Microsized Formulations of Indomethacin Using the In Vitro Dissolution Absorption System 2

The in vitro dissolution absorption system 2 (IDAS2), a recent invention comprised a conventional dissolution vessel containing 2 permeation chambers with Caco-2 cell monolayers mounted with their apical side facing the dissolution media, permits simultaneous measurement of dissolution and permeation of drugs from intact clinical dosage forms. The objectives of this study were (1) to assess the utility of IDAS2 in the determination of the effect of particle size on in vitro performance of indomethacin and (2) to find out whether the behavior in IDAS2 of 2 indomethacin products differing in particle size is correlated with their in vivo behavior. Indomethacin dissolution and permeation across Caco-2 cell monolayers were simultaneously measured in IDAS2; the dissolution and permeation profiles were simultaneously modeled using a simple two-compartment model. Compared to microsized indomethacin, the nanosized formulation increased the dissolution rate constant by fivefold, whereas moderately increasing the permeation rate constant and the kinetic solubility. As a result, the drug amount permeated across the Caco-2 cell monolayers doubled in the nanosized versus microsized formulation. The in vitro results showed a good correlation with in vivo human oral pharmacokinetic parameters, thus emphasizing the physiological relevance of IDAS2 data in predicting in vivo absorption.     

Coamorphous System of Florfenicol-Oxymatrine for Improving the Solubility and Dissolution Rate of Florfenicol: Preparation,Characterization and Molecular Dynamics Simulation

Coamorphous system has proved to be an effective approach to improve the solubility of BCSⅡ drugs. Florfenicol (FF) is a widely used veterinary antibiotic but has poor aqueous solubility. Therefore, the coamorphous system of florfenicol and oxymatrine (OMT) formulated at 1:1 and 1:2 M ratios were prepared by using solvent evaporation, followed by a series of characterization in terms of PXRD, DSC, FTIR and Raman spectroscopy. It was found that FF and OMT are miscible according to Hansen solubility parameters. The molecular electrostatic potential (MEP) and radial distribution function (RDF) analysis demonstrated the possible hydrogen bond interaction in coamorphous system, which was confirmed by FTIR and Raman spectra. The coamorphous FF-OMT (1:1) maintained stability for 60 days at 25 °C/0% RH and 30 days at 40 °C/75% RH, which may be attributed to better molecular miscibility of FF and OMT and the strong hydrogen bond of O–H (FF)?O–N (OMT) and N–H (FF)?O–N (OMT). In addition, the apparent solubility and permeability, dissolution and intrinsic dissolution rate (IDR) of the acquired coamorphous solids were obviously increased compared with crystalline FF. In conclusion, a drug-drug coamorphous formulation can be applied to improve the solubility and dissolution of crystalline FF.     

In Vitro Biopredictive Methods: A Workshop Summary Report

This workshop report summarizes the proceedings of Day 1 of a three-day workshop on “Current State and Future Expectations of Translational Modeling Strategies to Support Drug Product Development, Manufacturing Changes and Controls”. Physiologically based biopharmaceutics models (PBBM) are tools which enable the drug product quality attributes to be linked to the in vivo performance. These tools rely on key quality inputs in order to provide reliable predictions. After introducing the objectives of the workshop and the expectations from the breakout sessions, Day 1 of the workshop focused on the best practices and challenges in measuring in vitro inputs needed for modeling, such as the drug solubility, the dissolution rate of the drug product, potential precipitation of the drug and drug permeability. This paper reports the podium presentations and summarizes breakout session discussions related to A) the best strategies for determining solubility, supersaturation and critical supersaturation; B) the best strategies for the development of biopredictive (clinically relevant) dissolution methods; C) the challenges associated with describing gastro-intestinal systems parameters such as mucus, liquid volume and motility; and D) the challenges with translating biopharmaceutical measures of drug permeability along the gastrointestinal tract to a meaningful model parameter.     

Development and evaluation of niacinamide transdermal formulation by artificial membrane permeability

Despite many efforts to improve the transdermal permeability of drugs, most of them are blocked by the skin barrier. Niacinamide (NAC) is a Biopharmaceutics Classification System class I drug with high aqueous solubility and intestinal permeability. Due to the high solubility and intestinal permeability of NAC, the development of new formulations is insufficient as transdermal, injection etc. Thus, this study aimed to develop the novel NAC formulation with improved skin permeability and secured stability. The NAC formulation approach is to first select a solvent that improves skin permeability, and then select a second penetration enhancer to determine the final formulation. All formulations were evaluated for skin permeability using an artificial membrane (Strat-M®). The optimal formulation (non-ionic formulations (NF1) consisted of NAC/Tween®80 = 1:1 wt ratio in dipropylene glycol [DPG]) showed the highest permeability in all formulations in PBS buffer (pH 7.4). The thermal properties of NF1 were altered. Moreover, NF1 maintained a stable drug content, appearance, and pH value for 12 months. In conclusion, DPG had an excellent effect in increasing the NAC permeation, and Tween®80 played a boosting role. Through this study, an innovative NAC formulation was developed, and good results are expected for human transdermal research.     

Preparation and Evaluation of Quinapyramine Sulphate-Docusate Sodium Ionic Complex Loaded Lipidic Nanoparticles and Its Scale Up Using Geometric Similarity Principle

The objective of the present work is to prepare and evaluate ionically complexed Quinapyramine sulphate (QS) loaded lipid nanoparticles and its scale up using geometric similarity principle. Docusate sodium (DS), at a molar ratio of 1:2 of QS to DS, was used to prepare hydrophobic Quinapyramine sulphate-Docusate sodium (QS-DS) ionic complex. Based on the difference in total solubility parameter and polarity of QS-DS complex and different lipids, precirol was selected as a lipid for the preparation of lipidic nanoparticles. The particle size, zeta potential, and % entrapment efficiency (%EE) of QS-DS ionic complex loaded solid lipid nanoparticles (QS-DS-SLN) was found to be 250.10 ± 26.04 nm, ?27.41 ± 4.18 mV and 81.26 ± 4.67% respectively. FTIR studies confirmed the formation of QS-DS ionic complex. DSC and XRD studies revealed the amorphous nature of QS in QS-DS-SLN. The spherical shape of nanoparticles was confirmed by scanning electron microscopy. QS-DS-SLN showed sustained release of QS for up to 60 h. No significant difference was observed in particle size, zeta potential, and % entrapment efficiency of pilot-scale batch prepared by using rotational speed of 700 rpm. In conclusion, ionic complexation approach can be used to increase % EE of charged drugs into lipid nanoparticles.     

Impact of Precipitation of Antibody Therapeutics After Subcutaneous Injection on Pharmacokinetics and Immunogenicity

Antibody therapeutics with poor solubility in the subcutaneous matrix may carry unintended risks when administered to patients. The objective of this work was to estimate the risk of antibodies that precipitate in vitro at neutral pH by determining the impact of poor solubility on distribution of the drug from the injection site as well as immunogenicity in vivo. Using fluorescence imaging in a mouse model, we show that one such precipitation-prone antibody is retained at the injection site in the subcutaneous space longer than a control antibody. In addition, we demonstrate that retention at the injection site through aggregation is concentration-dependent and leads to macrophage association and germinal center localization. Although there was delayed disposition of the aggregated antibody to draining lymph nodes, no overall impact on the immune response in lymph nodes, systemic exposure of the antibody, or enhancement of the anti-drug antibody response was evident. Unexpectedly, retention of the precipitated antibody in the subcutaneous space delayed the onset of the immune response and led to an immune suppressive response. Thus, we conclude that precipitation due to poor solubility of high doses of antibody formulations delivered subcutaneously may not be of special concern in terms of exposure or immunogenicity.     

基于HPMCAS载体的依非韦伦固体分散体溶出模式研究

目的 以依非韦伦为原料药、不同规格（L、M、H）HPMCAS为载体，采用喷雾干燥法制备固体分散体并对其溶出模式进行初步探究。方法 通过X射线粉末衍射（XRPD）、扫描电子显微镜（SEM）对固体分散体理化性质进行制剂学表征；以动力溶解度为指标考察不同药载比、不同规格HPMCAS固体分散体的溶出情况；通过粒度分析仪和透射电子显微镜（TEM）、SEM探讨固体分散体溶出时的不同模式。结果 XRPD分析显示，固体分散体中药物以无定形的形态分散在HPMCAS中；SEM分析显示，L、M、H规格HPMCAS与依非韦伦形成的固体分散体均具有"萎缩葡萄干"形态；在pH 6.8磷酸缓冲盐溶液中溶出时，药载比1：6的固体分散体溶出好，药载比1：1.5的固体分散体溶出差且相同药载比时L规格HPMCAS的固体分散体溶出更快。结论 以不同规格HPMCAS为载体制备的依非韦伦固体分散体在pH 6.8磷酸缓冲盐溶液中溶出时，存在多种溶出模式。药载比1：6时，L、M规格HPMCAS的固体分散体以药物纳米颗粒的形式溶出；药载比1：1.5时，L、M规格HPMCAS的固体分散体存在类似溶蚀的溶出模式，药物从载体骨架中释放。     

An Integrated Analysis of Solid Form Change Impact on Solubility and Permeability: Case Study of Oral Exposure in Rats of an RAR Related Orphan Receptor C Inhibitor

It is well acknowledged that the oral absorption of a drug can be influenced by its solubility, which is usually associated with its solid form properties. G1032 is a retinoic acid–related orphan receptor inverse agonist. Crystalline solid (form A) was identified with an aqueous solubility of 130 μg/mL. This form was used in an oral dose escalation study in rodents up to 300 mg/kg and achieved good exposures. Later on, a more stable crystalline hydrate (form B) was identified and the aqueous solubility was reduced to 55 μg/mL. A modeling exercise suggested that this solubility change would cause a 2-fold decrease in exposure at tested doses; however, the actual reduction was far larger than the model predicted. At high dose, exposure was found to be reduced by almost 10-fold. A parameter sensitivity analysis suggested that such a drop in exposure could be associated with permeability reduction as well. More in vitro permeability experiments were performed, indicating G1032 was an efflux transporter substrate. This finding was integrated into the modeling and the design for in vivo studies. Data obtained from those studies allowed us to better understand the causes of the higher-than-expected exposure change and enabled decision-making.     

Vegetable Oil-based Hybrid Submicron Particles Loaded with JMV5038: A Promising Formulation against Melanoma

The aim of this work was to carry out a preformulation study on JMV5038 as a new potent cytotoxic agent, and to develop its formulation within vegetable oil-based hybrid submicron particles (HNP) in order to obtain a versatile dosage form against melanoma. JMV5038 was first characterized through physico-chemical tests and it exhibited high melting point and logP value, an important pH-sensitivity that led to the formation of well-identified degradation products at low pH, as well as a substantial solubility value in silylated castor oil (ICO). Then, JMV5038-loaded HNP were formulated through a thermostabilized emulsion process based on the sol-gel cross-linking of ICO. They showed high loading efficiency and their in vitro release kinetic assessed in a biorelevant PBS/octanol biphasic system showed a constant sustained release over one month. The cytotoxic activity and cytocompatibility of HNP were evaluated on A375 melanoma cells and NIH 3T3 cells, respectively. JMV5038-loaded HNP exhibited a slightly enhanced cytotoxic activity of JMV5038 on melanoma cells while demonstrating their safety on NIH 3T3 cells. In conclusion, JMV5038-loaded HNP proved to be an efficient and safe drug subcutaneous delivery system that will be interesting to evaluate through preclinical studies.     

Mechanism of Drug Release From Temperature-Sensitive Formulations Composed of Low-Melting-Point Microcrystalline Wax

It was reported that wax matrix (WM) particles composed of low-melting-point microcrystalline wax showed unique release behaviors; the particles released only a small amount of the entrapped drug (non–diffusion-controlled release) at 37°C, whereas it showed comparatively fast drug release in a diffusion-controlled manner at 25°C. However, the mechanism of the drug release is still unclear. The objective of this study was to determine the mechanism of drug release from the WM particles using X-ray computed tomography. In the WM particles collected during dissolution tests at 25°C, the void space derived from drug release increased with increasing time, and there was no change in the structure, indicating that the WM particles released drug while maintaining the particle shape at 25°C. In the WM particles collected during dissolution tests at 37°C, the void space was confirmed at initial time point; however, at subsequent time points, the void space was disappeared, and the roughness of the surface was evident. This structural change may have blocked the conveyance pathway of the outer medium, which would inhibit the drug release. The difference between the drug-release mechanisms of the WM particles at the 2 temperatures will be valuable for developing cooling-triggered, temperature-sensitive formulations.     

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity,dissolution and stability testing

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r²) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.     

Improvement of Oral Bioavailability and Anti-Tumor Effect of Zingerone Self-Microemulsion Drug Delivery System

This study sought to prepare a self-microemulsion drug delivery system containing zingerone (Z-SMEDDS) to improve the low oral bioavailability of zingerone and anti-tumor effect. Z-SMEDDS was characterized by particle size, zeta potential and encapsulation efficiency, while its pharmacokinetics and anti-tumor effects were also evaluated. Z-SMEDDS had stable physicochemical properties, including average particle size of 17.29 ± 0.07 nm, the zeta potential of -22.81 ± 0.29 mV, and the encapsulation efficiency of 97.96% ± 0.02%. In vitro release studies have shown the release of zingerone released by Z-SMEDDS was significantly higher than free zingerone in different release media. The relative oral bioavailability of Z-SMEDDS was 7.63 times compared with free drug. Meanwhile, the half inhibitory concentration （IC50）of Z-SMEDDS and free zingerone was 8.45 μg/mL and 13.30 μg/mL, respectively on HepG2. This study may provide a preliminary basis for further clinical research and application of Z-SMEDDS.     

Lactoferrin-Loaded Alginate Microparticles to Target Clostridioides difficile Infection

Some forms of bovine lactoferrin (bLf) are effective in delaying Clostridioides difficile growth and preventing toxin production. However, therapeutic use of bLf may be limited by protein stability issues. The objective of this study was to prepare and evaluate colon-targeted, pH-triggered alginate microparticles loaded with bioactive bLf and to evaluate their anti-C difficile defense properties in vitro. Different forms of metal-bound bLf were encapsulated in alginate microparticles using an emulsification or internal gelation method. The microparticles were coated with chitosan to control protein release. In vitro drug release studies were conducted in pH-simulated gastrointestinal conditions to investigate the release kinetics of encapsulated protein. No significant release of metal-bound bLf was observed at acidic pH; however, on reaching simulated colonic pH, most of the encapsulated lactoferrin was released. The application of bLf (5 mg/mL) delivered from alginate microparticles to human intestinal epithelial cells significantly reduced the cytotoxic effects of toxins A and B as well as bacterial supernatant on Caco-2 and Vero cells, respectively. These results are the first to suggest that alginate-bLf microparticles show protective effects against C difficile toxin-mediated epithelial damage and impairment of barrier function in human intestinal epithelial cells. The future potential of lactoferrin-loaded alginate microparticles against C difficile deserves further study.     

Molecular Dynamics Simulation to Uncover the Mechanisms of Protein Instability During Freezing

Freezing is a common process applied in the pharmaceutical industry to store and transport biotherapeutics. Herewith, multi-scale molecular dynamics simulations of Lactate dehydrogenase (LDH) protein in phosphate buffer with/without ice formation performed to uncover the still poorly understood mechanisms and molecular details of protein destabilization upon freezing. Both fast and slow ice growing conditions were simulated at 243 K from one or two-side of the simulation box, respectively. The rate of ice formation at all-atom simulations was crucial to LDH stability, as faster freezing rates resulted in enhanced structural stability maintained by a higher number of intramolecular hydrogen bonds, less flexible protein's residues, lower solvent accessibility and greater structural compactness. Further, protein aggregation investigated by coarse-grained simulations was verified to be initiated by extended protein structures and retained by electrostatic interactions of the salt bridges between charged residues and hydrogen bonds between polar residues of the protein. Lastly, the study of free energy of dissociation through steered molecular dynamics simulation revealed LDH was destabilized by the solvation of the hydrophobic core and the loss of hydrophobic interactions. For the first time, experimentally validated molecular simulations revealed the detailed mechanisms of LDH destabilization upon ice formation and cryoconcentration of solutes.     

Formulation development and evaluation of lidocaine hydrochloride loaded in chitosan-pectin-hyaluronic acid polyelectrolyte complex for dry socket treatment

The main purpose of this study was to assess a lidocaine hydrochloride-loaded chitosan-pectin-hyaluronic polyelectrolyte complex for rapid onset and sustained release in dry socket wound treatment. Nine formulations (LCs) of lidocaine hydrochloride (LH) loaded into a chitosan–pectin–hyaluronic polyelectrolyte complex (PEC) were assessed using full factorial design (two factors × three levels). The formulations ranged between 4 and 10% w/w LH and 0.5–1.5% w/w HA. The following physicochemical properties of LCs were characterized: size, zeta potential, % entrapment efficiency, viscosity, mucoadhesiveness, % drug release, morphology, storage stability, and cytotoxicity. The particle size, zeta potential, % EE, viscosity, and % mucoadhesion increased with increasing LH and HA concentrations. Rapid release of LH followed a zero-order model, and a steady-state percentage of the drug was released over 4 h. LCs were found to be non-cytotoxic compared to LH solution. LH loaded into PEC demonstrated appropriate characteristics—including suitable rate of release—and fit a zero-order model. Furthermore, it was not cytotoxic and showed good stability in a high-HA formula, making it a promising candidate for future topical oral formulations.     

Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values (R² = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.     

Design and Optimization of a Novel Strategy for the Local Treatment of Helicobacter pylori Infections

Infections with Helicobacter pylori are a global challenge. Currently, H. pylori infections are treated systemically, but the eradication rates of the different therapy regimens are declining due to the growing number of bacterial strains resistant to major antibiotics. Here, we present a strategy for the local eradication of H. pylori by the use of Penicillin G sodium (PGS). In vitro experiments revealed that PGS shows high antibiotic activity against resistant strains of Helicobacter pylori with a minimum inhibitory concentration (MIC) of 0.125 μg/ml. In order to provide luminal concentrations above the MIC for longer periods of time, an extended release tablet was developed. Alkalizers were included to prevent acidic degradation of PGS within the tablet matrix. Out of the tested alkalizers MgO, l-Lysine, NaHCO3, and Na2CO3 NaHCO3 provided the strongest rise in pH inside the hydrated matrix when tested in simulated gastric fluid. Better PGS stability can mainly reasoned from that, addition of MgO resulted in high pH values within the matrix, causing basic degradation of PGS. This work is a first step towards the use of extended release tablets containing PGS for the local treatment of H. pylori as a safe and cost-effective alternative to common systemic treatment regimens.     

Binding Characterization of Aptamer-Drug Layered Microformulations and In Vitro Release Assessment

Efficient delivery of adequate active ingredients to targeted malignant cells is critical, attributing to recurrent biophysical and biochemical challenges associated with conventional pharmaceutical delivery systems. These challenges include drug leakage, low targeting capability, high systemic cytotoxicity, and poor pharmacokinetics and pharmacodynamics. Targeted delivery system is a promising development to deliver sufficient amounts of drug molecules to target cells in a controlled release pattern mode. Aptameric ligands possess unique affinity targeting capabilities which can be exploited in the design of high pay-load drug formulations to navigate active molecules to the malignant sites. This study focuses on the development of a copolymeric and multifunctional drug-loaded aptamer-conjugated poly(lactide-co-glycolic acid)–polyethylenimine (PLGA-PEI) (DPAP) delivery system, via a layer-by-layer synthesis method, using a water-in-oil-in-water double emulsion approach. The binding characteristics, targeting capability, biophysical properties, encapsulation efficiency, and drug release profile of the DPAP system were investigated under varying conditions of ionic strength, polymer composition and molecular weight (MW), and degree of PEGylation of the synthetic core. Experimental results showed increased drug release rate with increasing buffer ionic strength. DPAP particulate system obtained the highest drug release of 50% at day 9 at 1 M NaCl ionic strength. DPAP formulation, using PLGA 65:35 and PEI MW of ∼800 Da, demonstrated an encapsulation efficiency of 78.93%, and a loading capacity of 0.1605 mg bovine serum albumin per mg PLGA. DPAP (PLGA 65:35, PEI MW∼25 kDa) formulation showed a high release rate with a biphasic release profile. Experimental data depicted a lower targeting power and reduced drug release rate for the PEGylated DPAP formulations. The outcomes from the present study lay the foundation to optimize the performance of DPAP system as an effective synthetic drug carrier for targeted delivery.