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INTRODUCTION: Human Immunodeficiency Virus (HIV) infection is still a major global problem, whose drug treatment consists of prophylactic prevention and antiretroviral combination therapy for better pharmacological efficacy and control of the circulating virus. However, there are still pharmacological problems that need to be overcome, such as low aqueous solubility of drugs, toxicity, and low patient adherence. Drug delivery technologies can be used to overcome these barriers. OBJECTIVE: This review summarized the latest drug delivery systems for HIV treatment. Initially, an overview of the current therapy was presented, along with the problems it presents. Then, the latest drug delivery systems used to overcome the challenges imposed in conventional HIV therapy were discussed. CONCLUSION: This review examines innovative approaches for HIV treatment, where various drug delivery systems have shown significant advantages, such as high drug encapsulation, improved solubility, and enhanced bioavailability both in vitro and in vivo. Strategies like cyclodextrins, solid dispersions, microneedles, and nanoparticles are explored to address challenges in drug solubility, bioavailability, and administration routes. Despite progress, obstacles like limited clinical trials and industrial scalability hinder the widespread adoption of these formulations, emphasizing the need for further research and collaboration to optimize and ensure accessibility of innovative HIV therapies, mainly in regions where access to HIV treatment is scarce and remains a challenge.

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This study aims to investigate key variables affecting the dissolution of amorphous pharmaceuticals. We examined sample treatment methods (centrifugation vs syringe filtration), time delays between sample collection and processing (immediate, 2, or 24 h), and different sample preparations (bare powder, capsules, or tablets). These factors were evaluated through both sink and nonsink dissolution experiments, using controlled supersaturation conditions (sink index ≈ 0.1) with amorphous solid dispersions (ASDs) containing low-substituted hydroxypropyl cellulose (L-HPC) and either indomethacin or posaconazole as model drugs. Our results highlighted the significant impact of syringe filtration on nonsink dissolutions, particularly the notable reduction in dissolved drug concentration, possibly due to filtration-induced precipitation. Moreover, introducing a delay of 2 or 24 h between sample collection and quantitation under nonsink conditions led to substantial concentration changes. This effect was not as pronounced when samples underwent centrifugation, and only the analysis was delayed for 2 h. The findings also emphasize the importance of accounting for delays introduced by pharmaceutical formulations, particularly in assessing the kinetic-solubility profiles of ASDs. This research offers valuable insights into the field of ASDs, enhancing our understanding of how these variables can influence dissolution results.

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Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.

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INTRODUCTION: Leprosy is a neglected, infectious, granulomatous and chronic disease caused by the pathological agent Mycobacterium leprae. The course of the disease is more aggressive in patients under 15 years of age, but the current treatment offered worldwide consists of solid forms, by the combination of antibiotics such as rifampicin, clofazimine and dapsone. This represents results in lack of adherence in pediatric patients and drug therapy failure, although numerous formulations and technologies have already been developed. AREA COVERED: This study aims to analyze the technological evolution of the pharmaceutical treatment of leprosy, aimed at children. A review of patents around the world was conducted to look for technical and clinical aspects of formulations and devices. EXPERT OPINION: Innovative formulations for pediatric patients were classified according to the routes of administration as oral, inhalable, injectable and transdermal. The formulations were organized as alternatives for pediatric therapy, taking into account the physicochemical aspects of drugs and the physiological aspects of pediatric patients. Among the difficulties for the patented formulations to reach the market, of special note is the low stability of the physicochemical characteristics of the drugs. Optimization of formulations would favor the pediatric treatment of leprosy, aiming at therapeutic success.

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Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.

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BACKGROUND: Tuberculosis is a chronic respiratory disease caused by Mycobacterium tuberculosis. The common treatment regimens of tuberculosis are lengthy with adverse side effects, low patient compliance, and antimicrobial resistance. Drug delivery systems (DDSs) can overcome these limitations. OBJECTIVE: This review aims to summarize the latest DDSs for the treatment of tuberculosis. In the first section, the main pharmacokinetic and pharmacodynamic challenges posed by the innate properties of the drugs are put forth. The second section elaborates on the use of DDS to overcome the disadvantages of the current treatment of tuberculosis. CONCLUSION: We reviewed research articles published in the last 10 years. DDSs can improve the physicochemical properties of anti-tuberculosis drugs, improving solubility, stability, and bioavailability, with better control of drug release and can target alveolar macrophages. However, more pre-clinical studies and robust bio-relevant analyses are needed for DDSs to become a feasible option to treat patients and attract investors.

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Enoxaparin is an effective biological molecule for prevention and treatment of coagulation disorders. However, it is poorly absorbed in the gastrointestinal tract. In this study, we developed an Eudragit® L100 coated chitosan core shell nanoparticles for enoxaparin oral delivery (Eud/CS/Enox NPs) through a completely eco-friendly method without employing any high-energy homogenizer technique and any organic solvents. Spherical nanocarriers were successfully prepared with particle size lower than 300 nm, polydispersity index about 0.12 and zeta potential higher than +25 mV, entrapment efficiency greater than 95% and the in vitro release behavior confirms the good colloidal stability and the successful Eudragit® L100 coating process demonstrated by negligible cumulative enoxaparin release (<10%) when the particles are submitted to simulated gastric fluid conditions. Finally, we demonstrated that the core-shell structure of the particle influenced the drug release mechanism of the formulations, indicating the presence of the Eudragit® L100 on the surface of the particles. These results suggested that enteric-coating approach and drug delivery nanotechnology can be successfully explored as potential tools for oral delivery of enoxaparin.

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Trees of the genus Sterculia produce polysaccharide-rich exudates, such as karaya gum (Sterculia urens), chicha gum (Sterculia striata), and Sterculia foetida gum. These anionic biomaterials are biodegradable, with high viscosity, low toxicity, and gelling properties in aqueous media. According to these properties, they show promising applications as a polymer matrix for use in drug delivery systems. For this application, both the chemically modified and the unmodified polysaccharide are used. This review focuses on analyzing the state of the art of recent studies on the use of Sterculia gums in a variety of pharmaceutical forms, such as tablets, hydrogels, micro/nanoparticles, and mucoadhesive films. Sterculia gums-based delivery systems have potential to be explored for new drug delivery systems.

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We developed a new hydrophobic polymer based on angico gum (AG), and we produced new nanoparticles to expand the applications of natural polysaccharides in nanomedicine. Phthalate angico gum (PAG) was characterized by 1H NMR, FTIR, elementary analysis, solubility, XRD, and TG. PAG was a hydrophobic and semi-crystalline material, a relevant characteristic for drug delivery system applications. As a proof of concept, nevirapine (NVP) was selected for nanoparticles development. Plackett-Burman's experimental design was used to understand the influence of several factors in nanoparticles production. PAG proved to be a versatile material for producing nanoparticles with different characteristics. Optimized nanoparticles were produced using desirability parameters. NVP-loaded PAG nanoparticles formulation showed 202.1 nm of particle size, 0.23 of PDI, -17.1 of zeta potential, 69.8 of encapsulation efficiency, and promoted modified drug release for 8 h. Here we show that PAG presents as a promising biopolymer for drug delivery systems.

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OBJECTIVE: To perform the solid-state characterization and the in vitro-in vivo correlation (IVIVC) of three batches of efavirenz (EFV) active pharmaceutical ingredients. SIGNIFICANCE: EFV is an effective anti-HIV drug. Due to the poor aqueous solubility, the rate and extent of EFV absorption deeply depend on its dissolution characteristics. METHODS: Thermal analyses, x-ray diffraction, and particle size distribution were performed. The saturation solubility and dissolution profiles were assessed in 0.5% (w/v) sodium lauryl sulfate (SLS), fasted-state simulated intestinal fluid (FaSSIF), and fed-state simulated intestinal fluid (FeSSIF) using a flow-through cell. Each batch was orally administered to Wistar rats and the pharmacokinetic parameters were correlated with those obtained from in vitro dissolution. RESULTS: All batches of EFV consisted polymorph I. EFV-A presented the lowest particle size distribution [d(v,0.5) = 197.8 µm; d(v,0.9) = 444.6 µm] followed by EFV-B [d(v,0.5) = 223.9 µm; d(v,0.9) = 481.1 µm], and EFV-C [d(v,0.5) = 240.8 µm; d(v,0.9) = 497.3 µm]. The saturated solubility in FaSSIF was 36% and 40% of that in FeSSIF and SLS, respectively. EFV-A presented the fastest rate and largest extension of dissolution than EFV-B and C (79.15%, 69.93% and 54.22%, respectively, as well as the highest maximum plasma concentration. Levels B, C, and multiple-C of IVIVC models were achieved. CONCLUSION: The FaSSIF medium discriminated the dissolution profiles of EFV APIs. Small differences in particle size distribution had a significant impact on the biopharmaceutical parameters of EFV, suggesting that strict control of such parameter is an important aspect during API development and drug formulation.

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Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, 1H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of -31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease.

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The study objective is to describe patients and professionals' perspectives on the Tuberculosis Control Program (PCT) in Recife, Brazil, contributing to the program evaluation. A cross-sectional study was conducted in three purposively selected sites, representing the three levels of care in the public health system. All eligible PCT patients in sites A, B and C were invited to participate (n = 123). Physicians, nurses, pharmacists and community health agents providing care to PCT patients in these sites, plus their managers, were purposively selected. Data were collected by means of interviews with 44 patients and a questionnaire to 24 professionals. Instruments encompassed previously published items to capture stakeholders' perspectives (16 and 12 closed-questions, respectively), grouped into categories. The overall evaluation by patients was unsatisfactory (median score 35%; third quartile below 50%; interquartile range 21.9%). Analysis of scores by categories showed that opinions about organizational accessibility were significantly worse than about economic and geographical accessibility, taken together. Overall the median score attributed by professionals was 52% (third quartile below 65%). Professionals had significantly worse opinions about diagnosis, clinical and laboratory assistance. Patients and professionals' perspectives highlight potential opportunities for improvement. Our findings can be used by managers as a starting point for shared decision-making, potentially contributing to a better performance of the PCT in Recife and, consequently, reducing the risk posed by tuberculosis.

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Thalidomide (TLD) is used to treat erythema nodosum leprosum (ENL), multiple myeloma, aphthous ulceration and wasting syndrome in HIV patients. The API can be found in two crystalline habits known as α-TLD and ß-TLD. The saturation solubility (Cs) and the dissolution profiles under non-sink and sink conditions of both polymorphs were assessed. In addition, mini-capsules containing α-TLD or ß-TLD without excipients were orally given (10 mg/kg) to Wistar rats. An intravenous (i.v.) dose was also administrated (5 mg/kg). The Cs values for α-TLD and ß-TLD were not significantly different (α = 56.2 ±â€¯0.5 µg·mL-1; ß = 55.2 ±â€¯0.2 µg·mL-1). However, the dissolution profile of α-TLD presented the fastest rate and the largest extension of drug dissolution than that from ß-TLD (80% in 4 h versus 55% in 4 h). The α-TLD provided a more favorable pharmacokinetic than the ß-TLD (maximum plasma concentration - Cmax: 5.4 ±â€¯0.90 µg·mL-1versus 2.6 ±â€¯0.2 µg·mL-1; area under the curve of the concentration-time profile from time zero to infinity - AUC0-∞: 44.3 ±â€¯8.8 µg·h·mL-1versus 33.9 ±â€¯4.7 µg·h·mL-1; absolute bioavailability - F: 92.2 ±â€¯18.5% versus 70.5 ±â€¯9.9%, respectively). Drug suppliers and pharmaceutical companies should strictly control the technological processes involved in the TLD API synthesis as well as in the production of the pharmaceutical dosage form in order to guarantee the inter-batch homogeneity and therefore, product compliance.

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This work describes a solvent-free method for the chemical modification of cashew gum (Anacardium occidentale L.) using phthalic anhydride in different proportions with different reaction times. Four biopolymers were synthesized and characterized by FTIR, NMR, and elemental analysis. A computational chemistry study was conducted to understand better the reaction. Phthalated cashew gum was used in preparation of silver nanoparticles (AgNPs) by a conventional route, using sodium borohydride (NaBH4) as reducing agent, and for green route. AgNPs were evaluated for antimicrobial activity and characterized by UV-Vis spectroscopy, FTIR, nanoparticle tracking analysis, Zeta Potential analysis, and atomic force microscopy. AgNPs produced by the green route had an average size of 51.9 nm and Zeta Potential of -55.8 mV, and AgNPs produced by the conventional method had an average size of 47.7 nm and Zeta Potential of -39.3 mV. AgNPs synthesized using phthalated cashew gum showed antimicrobial activity against Staphylococcus aureus and Escherichia coli.

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Cashew gum (CG) is a biopolymer that presents a favorable chemical environment for structural modifications, which leads to more stable and resistant colloidal systems. The gum was subjected to an acetylation reaction using a fast, simple, solvent-free and low cost methodology. The derivative was characterized by infrared and NMR spectroscopy, elemental analysis, coefficient of solubility and zeta potential. The modified biopolymer was used as a platform for drug delivery systems using insulin as a model drug. Nanoparticles were developed through the technique of polyelectrolytic complexation and were characterized by size, surface charge, entrapment efficiency and gastrointestinal release profile. The nanoparticles presented size of 460 nm with a 52.5% efficiency of entrapment of insulin and the electrostatic stabilization was suggested by the zeta potential of + 30.6 mV. Sustained release of insulin was observed for up to 24 h. The results showed that acetylated cashew gum (ACG) presented potential as a vehicle for sustained oral insulin release.

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OBJECTIVE: To develop an analytical method to simultaneous quantification of benznidazole (BNZ) and posaconazole (POS) by high-performance liquid chromatography with diode-array detection (HPLC-DAD) using design of experiments. METHODS: Percentages of organic phase, buffer pH and flow rates of mobile phase were selected as independent variables by full factorial design (33), totaling 27 experiments. Significant factors were evaluated using factorial analysis of variance with 95% confidence level. Method optimization was performed using desirability profiles, considering BNZ/POS chromatographic resolution and peak areas. Further, the method was evaluated regarding its suitability and properly validated according to the international compendiums using the parameters: specificity, linearity, accuracy, precision, limit of detection and limit of quantification. RESULTS: The optimized method was achieved using Discovery® C8 column (250 mm × 4.6 mm; 5 µm particle size), methanol/acetate buffer (pH 3.5)(71:29) and detection at 260 nm. Retention times were 3.6 and 7.6 min for BNZ and POS, respectively, with good suitability of system and it was specific and linear (r2 >0.99) for both drugs, proving the efficiency of the method even in the presence of degradation products of POS. CONCLUSION: This new method is a great alternative to perform reliable, faster and cheaper analysis since the simultaneous quantification of the association BZN/POS is not reported yet in the literature.

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Olanzapine (OLZ), is used in the treatment of bipolar disorder and schizophrenia, diseases that present oxidative stress in their physiopathology. It has low aqueous solubility, which may lead to low oral bioavailability. The search of new drug delivery systems (DDSs) that may increase dissolution rate of OLZ, associated with the investigation of the antioxidant potential of the loaded-systems become of major importance to understand improvement in bipolar disorder and schizophrenia therapy. Thus, this study aimed to evaluate the in vitro antioxidant potential of two different Layered Double Hydroxides (LDH) loaded with 5% of OLZ (CaAl and NiAl), by radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl and nitric oxid); radical cation scavenging activity (2,2'-azino-bis3-ethylbenzthiazoline-6-sulfonic acid ABTS) and evaluation of inhibition capacity of lipid peroxidation by thiobarbituric acid (TBARS). The results showed that both obtained LDH systems presented in vitro antioxidant capacity when associated with OLZ in all methods performed, and this activity is more pronounced with the systems containing OLZ compared to pure drug. The systems with CaAl was shown to have increased antioxidant potential, compared to NiAl, increasing the antioxidant activity up to 40,83%, 15,84% and 16,73%, as showed by the DPPH, nitric oxide and TBARS tests, respectively. The results revealed that the use of LDHs as a functional excipient may be promising in the pharmaceutical industry for bipolar disorder and schizophrenia therapy.

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Posaconazole (PCZ) and benznidazole (BNZ) are known to show synergetic effect in treating the acute and chronic phases of Chagas disease, a neglected parasitic disease. However, as both compounds are poorly water soluble, the development of amorphous solid dispersions (ASDs) of a PCZ/BNZ fixed-dose combination in a water-soluble polymer becomes an attractive option to increase their apparent solubility and dissolution rate, potentially improving their oral bioavailability. The initial approach was to explore solvent evaporated solid dispertion (SD) systems for a PCZ/BNZ 50:50 (wt%) combination at several total drug loading levels (from SD with 10% to 50% drug loading) in water-soluble carriers, including polyvinylpyrrolidone (PVP K-30) and vinylpyrrolidone-vinyl acetate copolymer (PVPVA 64). Based on comparison of non-sink in vitro dissolution performance, ASD systems based on PVPVA was identified as the most effective carrier for a 50:50 (w/w %) fixed-dose combination of PCZ/BNZ to increase their apparent solubility and dissolution rate, mainly at 10% drug loading, which shows more expressive values of area under the curve (AUC) (7336.04 ±â€¯3.77 min.µL/mL for PCZ and 15,795.02 ±â€¯7.29 min.µL/mL for BNZ). Further characterization with polarized microscopy, powder X-ray diffraction, and thermal analysis reveals that there exists a threshold drug loading level at about 30% PCZ/BNZ, below which ASDs are obtained and above which a certain degree of crystallinity tends to result. Moreover, infrared spectroscopic analysis reveals the lack of hydrogen bonding interactions between the drugs (PCZ and BNZ) and the polymer (PVPVA) in the ASD, this is also confirmed through molecular dynamics simulations. The molecular modeling results further show that even in the absence of meaningful hydrogen bonding interactions, there is a greater tendency for PVPVA to interact preferentially with PCZ and BNZ through electrostatic interactions thereby contributing to the stability of the system. Thus, the present SD system has the advantage of presenting a fixed-dese combination of two synergistic antichagasic agents PCZ and BNZ together in amorphous form stabilized in the PVPVA matrix with enhanced dissolution, potentially improving their bioavailability and therapeutic activity in treating Chagas disease.

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Benznidazole (BNZ), the only commercialized antichagasic drug, and the antifungal compound posaconazole (PCZ) have shown synergistic action in the therapy of Chagas disease, however both active pharmaceutical ingredients (APIs) exhibit low aqueous solubility potentially limiting their bioavailability and therapeutic efficacy. In this paper, we report for the first time the formation of a eutectic mixture as well as an amorphous solid solution of PCZ and BNZ (at the same characteristic ratio of 80:20wt%), which provided enhanced solubility and dissolution rate for both APIs. This eutectic system was characterized by DSC and the melting points obtained were used for the construction of a phase diagram. The preservation of the characteristic PXRD patterns and the IR spectra of the parent APIs, and the visualization of a characteristic eutectic lamellar crystalline microstructure using Confocal Raman Microscopy confirm this system as a true eutectic mixture. The PXRD result also confirms the amorphous nature of the prepared solid solution. Theoretical chemical analyses indicate the predominance of π-stacking interactions in the amorphous solid solution, whereas an electrostatic interaction between the APIs is responsible for maintaining the alternating lamellar crystalline microstructure in the eutectic mixture. Both the eutectic mixture and the amorphous solid solution happen to have a characteristic PCZ to BNZ ratio similar to that of their pharmacological doses for treating Chagas disease, thus providing a unique therapeutic combination dose with enhanced apparent solubility and dissolution rate.

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