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1.
Nanoscale Adv ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39247861

RESUMEN

Mosquitoes are the most medically important arthropod vectors of several human diseases. These diseases are known to severely incapacitate and debilitate millions of people, resulting in countless loss of lives. Over the years, several measures have been put in place to control the transmission of mosquito-borne diseases, one of which is using repellents. Repellents are one of the most effective personal protective measures against mosquito-borne diseases. However, conventional delivery systems of repellents (e.g., creams, gels, and sprays) are plagued with toxicity and short-term efficacy issues. The application of biopolymeric and lipid-based systems has been explored over the years to develop better delivery systems for active pharmaceutical ingredients including mosquito repellents. These delivery systems (e.g., solid lipid micro/nanoparticles, micro/nanoemulsions, or liposomes) possess desirable properties such as high biocompatibility, versatility, and controlled/sustained drug delivery, and thus are very important in tackling the clinical challenges of conventional repellent systems. Their capability for controlled/sustained drug release has improved patient compliance as it removes the need for consistent reapplication of repellents. They can also be engineered to reduce repellents' skin permeation, consequently improving their safety. However, despite the benefits that these systems offer very few of them have been successfully translated to the global market for commercial use, a vital challenge that previous reports have not thoroughly examined. The issue of limited clinical translation of novel repellent systems is a vital aspect to consider, as the ultimate goal is to move these systems from bench to bedside. As such, this study seeks to highlight the recent advances in the use of biopolymeric and lipid-based systems for the development of novel mosquito-repellent systems and also analyze the challenges that have limited the clinical translation of these systems while proposing possible strategies to overcome these challenges.

2.
Heliyon ; 10(8): e28872, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38655322

RESUMEN

5-flourouracil (5-FU) is typically modulated with leucovorin (LEU) in clinical practice to improve clinical efficacy and patient survival rates. However, this combination has undesirable side effects and makes 5-FU more toxic. Hence, integrating a vesicular system (proniosomes) with another delivery vehicle may improve drug targeting, while resolving the aforementioned drawbacks. This study aimed to engineer 5-FU/LEU proniosomes for possible delivery to the colon. The modified slurry approach was used to create drug-loaded proniosomes (150 mg/9 g of carrier) using both water-soluble (dextrin (DEX) and lactose (LAC)) and insoluble (Neusilin FH2 (NEU)) carriers. The powdered formulations were filled into Eudragit S100 (10 %)-coated capsules or Eudragit FS 30D capsules for enteric- or colon-specific delivery. In vitro evaluations (flow properties, powder X-ray diffractometry (XRD) analysis, particle size analysis, entrapment efficiency, drug release, scanning electron microscopy (SEM), polydispersity index, Fourier transform infrared spectroscopy (FTIR), and stability studies) were performed on the formulations. An in vitro cytotoxicity test [real-time cell assay (RTCA)] against HCT-116 colon cancer cell lines was performed using the optimized formulation. In vitro evaluations showed that the nanoparticles had good physicochemical properties. RTCA studies showed sustained cell death with the formulations compared to the pure drug and placebo. The sequential drug release of the colon-targeted capsules containing 5-FU and LEU- loaded proniosomes showed negligible drug release in SGF (pH 1.2) and phosphate buffer solution (pH 6.8) (approximately 11 %) but profound drug release (>80 %) at pH 7.4. Drug-loaded proniosomes engineered for colon targeting (Eudragit S100 (10 %) capsules or Eudragit FS 30D capsules) showed good colon-specific targeting and favorable in vitro cytotoxicity profiles.

4.
Pharmaceutics ; 15(10)2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37896176

RESUMEN

Bacteriophages (phages) are nano-sized viruses characterized by their inherent ability to live off bacteria. They utilize diverse mechanisms to absorb and gain entry into the bacterial cell wall via the release of viral genetic material, which uses the replication mechanisms of the host bacteria to produce and release daughter progeny virions that attack the surrounding host cells. They possess specific characteristics, including specificity for particular or closely related bacterial species. They have many applications, including as potential alternatives to antibiotics against multi-resistant bacterial pathogens and as control agents in bacteria-contaminated environments. They are ubiquitously abundant in nature and have diverse biota, including in the gut. Gut microbiota describes the community and interactions of microorganisms within the intestine. As with bacteria, parasitic bacteriophages constantly interact with the host bacterial cells within the gut system and have obvious implications for human health. However, it is imperative to understand these interactions as they open up possible applicable techniques to control gut-implicated bacterial diseases. Thus, this review aims to explore the interactions of bacteriophages with bacterial communities in the gut and their current and potential impacts on human health.

5.
Nanoscale Adv ; 5(18): 4628-4648, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37705787

RESUMEN

Retinoblastoma is the most common intraocular malignancy in children. The treatment of this rare disease is still challenging in developing countries due to delayed diagnosis. The current therapies comprise mainly surgery, radiotherapy and chemotherapy. The adverse effects of radiation and chemotherapeutic drugs have been reported to contribute to the high mortality rate and affect patients' quality of life. The systemic side effects resulting from the distribution of chemotherapeutic drugs to non-cancerous cells are enormous and have been recognized as one of the reasons why most potent anticancer compounds fail in clinical trials. Nanoparticulate delivery systems have the potential to revolutionize cancer treatment by offering targeted delivery, enhanced penetration and retention effects, increased bioavailability, and an improved toxicity profile. Notwithstanding the plethora of evidence on the beneficial effects of nanoparticles in retinoblastoma, the clinical translation of this carrier is yet to be given the needed attention. This paper reviews the current and emerging treatment options for retinoblastoma, with emphasis on recent investigations on the use of various classes of nanoparticles in diagnosing and treating retinoblastoma. It also presents the use of ligand-conjugated and smart nanoparticles in the active targeting of anticancer and imaging agents to the tumour cells. In addition, this review discusses the prospects and challenges in translating this nanocarrier into clinical use for retinoblastoma therapy. This review may provide new insight for formulation scientists to explore in order to facilitate the development of more effective and safer medicines for children suffering from retinoblastoma.

6.
Recent Adv Drug Deliv Formul ; 17(3): 228-240, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37711010

RESUMEN

OBJECTIVE: This study aimed to evaluate Cola acuminata gum (CAG) for the formulation of mucoadhesive sustained-release matrix tablets of diclofenac sodium. METHODS: Different batches of granules containing CAG and 100 mg of DS in ratios 0.5:1, 1:1, 2:1, and 3:1 were prepared, compressed into tablets, and evaluated for mucoadhesive strength, swelling index, and drug release in SGF (pH 1.2) and SIF (pH 7.4). RESULTS: Swelling indices and mucoadhesive strengths of the tablets were pH-dependent. Swelling indices of 56 ± 2.03 to 121 ± 2.19% and mucoadhesive strengths of 7.25 ± 1.45 to 15.43 ± 2.71 g/cm2 obtained at pH 7.4 were significantly higher (p<0.05) than swelling indices of 25 ± 2.43 to 47 ± 3.15% and mucoadhesive strengths of 5.52 ± 0.76 to 9.22 ± 1.95 g/cm2 obtained at pH 1.2. The percentage release of DS from the matrix tablets at pH 1.2 after 2 h (T2h) was insignificant. However, the percentage of drug release at pH 7.4 was significant for all the batches and dependent on the CAG concentration. The drug release was in the order of batches containing 3 g (80.44 ± 7.75) < 2 g (86.35 ± 5.65) < 1 g (90.08 ± 6.14) < 0.5 g (99.70 ± 3.90). The time for maximum drug release was 7 h (T7h) for CAG containing 0.5 g and 10 h (T10h) for other batches. CONCLUSION: This study showed that CAG could be useful for mucoadhesive sustained drug delivery.


Asunto(s)
Cola , Diclofenaco , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Comprimidos
7.
Heliyon ; 9(6): e16963, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37484262

RESUMEN

This research investigates the potentials of prodigiosin(PG) derived from bacteria and its formulations against triple-negative breast (TNB), lung, and colon cancer cells. The PG was extracted from S. marcescens using continuous batch culture, characterized, and formulated into lyophilized parenteral nanoparticles (PNPs). The formulations were characterized with respect to entrapment efficiency (EE), DSC, FT-IR, TEM, and proton nuclear magnetic resonance (1H NMR) spectroscopy. In vitro drug release was evaluated in phosphate buffer (pH 7.4) while acute toxicity, hematological and histopathological studies were performed on rats. The in vitro cytotoxicity was evaluated against TNB (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines. High EE (92.3 ± 12%) and drug release of up to 89.4% within 8 h were obtained. DSC thermograms of PG and PG-PNPs showed endothermic peaks indicating amorphous nature. The FT-IR spectrum of PG-PNPs revealed remarkable peaks of pure PG, indicating no strong chemical interaction between the drug and excipients. The TEM micrograph of the PG-PNPs showed nano-sized formulations (20-30 nm) whose particles were mostly lamellar and hexagonal structures. The 1H NMR result revealed the chemical structure of PG showing all assigned proton chemical shifts. Toxicity results of the PG and its formulation up to a concentration of 5000 mg/kg showed insignificant vacuolar changes of hepatocytes in the liver, with normal renal medulla and cortex in the kidney. The PG and PG-PNPs inhibited the growth of breast, lung, and colon cell lines. The nano-sized lipid formulation (PG-PNPs) showed potential in PG delivery and cancer treatments.

8.
J Control Release ; 354: 465-488, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36642250

RESUMEN

Diseases affecting the anterior segment of the eye are the primary causes of vision impairment and blindness globally. Drug administration through the topical ocular route is widely accepted because of its user/patient friendliness - ease of administration and convenience. However, it remains a significant challenge to efficiently deliver drugs to the eye through this route because of various structural and physiological constraints that restrict the distribution of therapeutic molecules into the ocular tissues. The bioavailability of topically applied ocular medications such as eye drops is typically less than 5%. Developing novel delivery systems to increase the retention time on the ocular surfaces and permeation through the cornea is one of the approaches adopted to boost the bioavailability of topically administered medications. Drug delivery systems based on nanotechnology such as micelles, nanosuspensions, nanoparticles, nanoemulsions, liposomes, dendrimers, niosomes, cubosomes and nanowafers have been investigated as effective alternatives to conventional ocular delivery systems in treating diseases of the anterior segment of the eye. This review discussed different nanotechnology-based delivery systems that are currently investigated for treating and managing diseases affecting the anterior ocular tissues. We also looked at the challenges in translating these systems into clinical use and the prospects of nanocarriers as a vehicle for the delivery of phytoactive compounds to the anterior segment of the eye.


Asunto(s)
Sistemas de Liberación de Medicamentos , Oftalmopatías , Humanos , Oftalmopatías/tratamiento farmacológico , Ojo , Nanotecnología , Liposomas/uso terapéutico , Córnea , Administración Oftálmica
9.
Pharmaceuticals (Basel) ; 15(11)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36355503

RESUMEN

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in-use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in-use stability protocols should be preferred in the stability evaluation of pediatric formulations.

10.
Heliyon ; 8(11): e11390, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36387434

RESUMEN

The current study was to improve and control aceclofenac delivery prepared as biopolymer-based microparticles for effective colon-targeted drug delivery using modified gelatin capsules (MGCs) at different time intervals developed in two batches (C1 and C2). Microparticles were formulated with extracted mucuna gum using liquid paraffin oil (AC.LPO) and soybean oil (AC.SO) and evaluated in vitro for physicochemical performance and in vivo in rats. Encapsulation efficiency ranges from 54.48 ± 0.21% to 82.83 ± 0.22% for AC.LPO and 52.64 ± 0.11% to 80.36 ± 0.22% for AC.SO. SEM showed oblong and irregular shapes with porous and cracked surfaces. DSC showed low enthalpy and a very broad endothermic peak depicting high amorphous property. Delayed drug release was observed in the upper gastrointestinal tract with sustained release depicted in the lower gastrointestinal tract (GIT) using 3 and 9-h batch C1 of MGCs. AC.SO exhibited significantly (p < 0.05) higher anti-inflammatory activity (86%) than AC.LPO (77%). Hence, aceclofenac colon delivery could be improved and controlled using biopolymer-based colon-targeted microparticles delivered with MGCs.

11.
Front Pharmacol ; 13: 874510, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36160424

RESUMEN

Cancer is an important cause of morbidity and mortality worldwide, irrespective of the level of human development. Globally, it was estimated that there were 19.3 million new cases of cancer and almost 10 million deaths from cancer in 2020. The importance of prevention, early detection as well as effective cancer therapies cannot be over-emphasized. One of the important strategies in cancer therapy is targeted drug delivery to the specific tumor sites. Nanogels are among the several drug delivery systems (DDS) being explored as potential candidates for targeted drug delivery in cancer therapy. Nanogels, which are new generation, versatile DDS with the possession of dual characteristics of hydrogels and nanoparticles have shown great potential as targeted DDS in cancer therapy. Nanogels are hydrogels with a three-dimensional (3D) tunable porous structure and a particle size in the nanometre range, from 20 to 200 nm. They have been visualized as ideal DDS with enormous drug loading capacity, and high stability. Nanogels can be modified to achieve active targeting and enhance drug accumulation in disease sites. They can be designed to be stimulus-responsive, and react to internal or external stimuli such as pH, temperature, light, redox, thus resulting in the controlled release of loaded drug. This prevents drug accumulation in non-target tissues and minimizes the side effects of the drug. Drugs with severe adverse effects, short circulation half-life, and easy degradability by enzymes, such as anti-cancer drugs, and proteins, are suitable for delivery by chemically cross-linked or physically assembled nanogel systems. This systematic review summarizes the evolution of nanogels for targeted drug delivery for cancer therapy over the last decade. On-going clinical trials and recent applications of nanogels as targeted DDS for cancer therapy will be discussed in detail. The review will be concluded with discussions on safety and regulatory considerations as well as future research prospects of nanogel-targeted drug delivery for cancer therapy.

12.
Recent Adv Antiinfect Drug Discov ; 17(2): 103-117, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35670344

RESUMEN

BACKGROUND: Artemisininbased combination therapies (ACTs) typified by dihydroartemisinin- piperaquine phosphate are first-line drugs used in the treatment of Plasmodium falciparum malaria. However, the emergence of drug resistance to ACTs shows the necessity to develop novel sustained release treatments in order to ensure maximum bioavailability. OBJECTIVES: To formulate dihydroartemisinin (DHA)-piperaquine phosphate (PQ) sustained release tablets based on solidified reverse micellar solutions (SRMS). METHODS: The SRMS was prepared by fusion using varying ratios of Phospholipon® 90H and Softisan® 154 and characterised. The tablets were prepared by using an in-house made and validated mould. The formulations were tested for uniformity of weight, hardness, friability, softening time, erosion time and in vitro-in vivo dissolution rate. Antimalarial properties were studied using modified Peter's 4-days suppressive test in mice. One-way analysis of variance (ANOVA) was used in the analysis of results. RESULTS: Smooth caplets, with average weight of 1300 ± 0.06 mg to 1312 ± 0.11 mg, drug content of 61 mg for DHA and t 450 mg for PQ. Tablet hardness ranged from 7.1 to 9.0 Kgf and softening time of 29.50 ± 1.90 min. Erosion time of 62.00 ± 2.58 to 152.00 ± 1.89 min were obtained for tablets formulated with Poloxamer 188 (Batches R2, S2 and T2) which significantly reduced the softening and erosion time (p < 0.05). In vitro release showed that the optimized formulations had a maximum release at 12 h. Formulations exhibited significantly higher parasitaemia clearance and in vivo absorption compared to marketed formulations at day 7 (p < 0.05). CONCLUSION: DHA-PQ tablets based on SRMS were much easier and relatively cheaper to produce than compressed tablets. They also showed exceptionally better treatment of malaria owing to their sustained release properties and improved bioavailability and are recommended to Pharmaceutical companies for further studies.


Asunto(s)
Antimaláricos , Artemisininas , Ratones , Animales , Antimaláricos/farmacología , Preparaciones de Acción Retardada , Artemisininas/farmacología , Comprimidos , Lípidos , Fosfatos
13.
Recent Adv Drug Deliv Formul ; 16(3): 217-233, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35473532

RESUMEN

BACKGROUND: Previous folkloric and experimental reports have demonstrated the antimalarial efficacy of Azadirachta indica (AZA) extracts. However, one of the major challenges facing its application for the clinical treatment of malaria is the design of an acceptable dosage form. OBJECTIVE: Consequently, we developed AZA extract-loaded nanostructured lipid carriers (NLC) for the formulation of suppositories, denoted as nanosuppositories, for intrarectal treatment of malaria. METHODS: Various batches of NLC-bearing AZA extract were formulated based on lipid matrices prepared using graded concentrations of Softisan®154 and Tetracarpidium conophorum or walnut oil. NLC was investigated by size and differential scanning calorimetry (DSC). Suppository bearing AZA extract-loaded NLC was developed using cocoa butter or theobroma oil, and their physicochemical properties were profiled. In vitro drug release and in vivo antimalarial activity (using Plasmodium berghei-infected mice) were investigated. RESULTS: NLCs exhibited sizes in nanometers ranging from 329.5 - 806.0 nm, and were amorphized as shown by DSC thermograms. Nanosuppositories were torpedo- or bullet- shaped, weighing 138 - 368 mg, softened/liquefied between 4.10 - 6.92 min, and had controlled release behaviour. In vivo antimalarial study revealed excellent antimalarial efficacy of the nanosuppositories comparable with a commercial brand (Plasmotrim®) and better than the placebo (unloaded nanosuppository), and without toxic alterations of hepatic and renal biochemical factors. CONCLUSION: Thus, AZA extract could be rationally loaded in nanostructured lipid carriers (NLC) for further development as nanosuppository and deployed as an effective alternative with optimum convenience for intrarectal treatment of malaria.


Asunto(s)
Antimaláricos , Azadirachta , Malaria , Ratones , Animales , Antimaláricos/farmacología , Malaria/tratamiento farmacológico , Plasmodium berghei , Lípidos/química
14.
Heliyon ; 8(3): e09099, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35309393

RESUMEN

Metformin hydrochloride (MH) is a widely used oral biguanide antihyperglycemic (antidiabetic) drug with poor bioavailability which necessitates the development of novel drug delivery systems such as PEGylated solid lipid nanoparticles for improving its therapeutic activity. The aim of this study was to formulate, characterize and evaluate in vitro and in vivo pharmacodynamic properties of metformin-loaded PEGylated solid lipid nanoparticles (PEG-SLN) for improved delivery of MH. The lipid matrices (non-PEGylated lipid matrix and PEGylated lipid matrices) used in the formulation of both non-PEGylated (J0) and PEGylated SLNs (J10, J20, J40) were prepared by fusion using beeswax and Phospholipon ® 90H at 7:3 ratio with or without polyethylene glycol (PEG) 4000 (0, 10, 20 and 40% w/w), respectively. Representative lipid matrices (LM and PEG-LM) were loaded with MH by fusion and then characterized by differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy. The PEG-SLNs were prepared by high shear hot homogenization using the lipid matrices (5% w/w), drug (MH) (1.0% w/w), sorbitol (4% w/w) (cryoprotectant), Tween ® 80 (2% w/w) (surfactant) and distilled water (q.s to 100% w/w) (vehicle). The non-PEGylated and PEGylated SLNs (J0, J10, J20, J40)) were characterized with respect to encapsulation efficiency (EE%), loading capacity (LC), morphology by scanning electron microscopy (SEM), mean particle size (Zav) and polydispersity indices (PDI) by photon correlation spectroscopy (PCS), compatibility by FT-IR spectroscopy and in vitro drug release in biorelevant medium. Thereafter, in vivo antidiabetic study was carried out in alloxanized rats' model and compared with controls (pure sample of MH and commercial MH- Glucophage®)). Solid state characterizations indicated the amorphous nature of MH in the drug loaded-lipid matrices. The PEG-SLNs were mostly smooth and spherical nanoformulations with Zav and PDI of 350.00 nm and 0.54, respectively, for non-PEGylated SLNs, and in the range of 386.80-783.10 nm and 0.592 to 0.752, respectively, for PEGylated SLNs. The highest EE% and LC were noted in batch J20 and were 99.28% and 16.57, respectively. There was no strong chemical interaction between the drug and excipients used in the preparation of the formulations. The PEGylated SLN (batch J40) exhibited the highest percentage drug released (60%) at 8 h. The PEGylated SLNs showed greater hyperglycemic control than the marketed formulation (Glucophage ®) after 24 h. This study has shown that metformin-loaded PEGylated solid lipid nanoparticles could be employed as a potential approach to improve the delivery of MH in oral diabetic management, thus encouraging further development of the formulations.

15.
Heliyon ; 8(3): e09100, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35313488

RESUMEN

Metformin hydrochloride (MTH) has been associated with poor/incomplete absorption (50-60%), low bioavailability, short half-life (0.4-0.5 h), high dosage and dose-related side effects. To overcome these barriers and improve oral bioavailability and efficacy of MTH, surface-modified nanostructured lipid carriers (NLCs) were developed. Lipid matrices composed of rational blends of beeswax and Phospholipon® 90H (as solid lipids) and Capryol-PGE 860 (as liquid lipid) were prepared by fusion, and the resultant lipid matrices were PEGylated to give 10, 20 and 40% PEGylated lipid matrices. MTH-loaded non-PEGylated and PEGylated NLCs were prepared via high-shear hot homogenization and characterized regarding particle properties and physicochemical performance. The encapsulation efficiencies (EE%) and loading capacities (LC) of the MTH-loaded NLCs were determined while the in vitro drug release was evaluated in phosphate buffered saline (PBS, pH 7.4). Antidiabetic and pharmacokinetics properties of the NLCs were ascertained in an alloxan-induced diabetic rats model after oral administration. The MTH-loaded NLCs were nanomeric (particle size: 184.8-882.50 nm) with low polydispersity index (0.368-0.687) and zeta potential (26.5-34.2 mV), irregular shape, amorphous nature with reduced crystallinity. The EE% and LC were >90 % and 16%, respectively. The formulations showed >65 % release over 12 h in a greater sustained manner than marketed MTH formulation (Glucophage®) as well as enhanced pharmacokinetics properties and sustained blood glucose lowering effect, even at reduced doses with PEGylated NLCs than Glucophage®. Thus, PEGylated NLC is a promising approach for improved delivery and oral bioavailability of MTH thus encouraging further development of the formulation.

16.
Biomed Res Int ; 2022: 8930709, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35118159

RESUMEN

PURPOSE: To assess the improvement in oral bioavailability and efficacy in systemic candidiasis treatment of miconazole nitrate (MN) formulations in murine models of candidiasis. METHODS: Selected formulations containing 5% of Softisan + Phospholipon 90H lipid matrix with 3% of MN (A 1), 5% of stearic acid + Phospholipon 90H lipid matrix with 3% of MN (B 1), and 5% Softisan + stearic acid + Phospholipon 90H with 3% of MN (C 1) from the in vitro investigation were used for the study. Their acute toxicity was assessed using Lorke's method (with slight modification) while bioavailability was determined using the bioassay method. The optimized batch (A 1) was tested in murine systemic candidiasis induced in cyclophosphamide-immunosuppressed mice. The mice were treated with a single oral dose (100 mg/kg) of the formulations for five days. Serum fungal counts (cfu/mL) were determined on days 1, 3, and 5 of the treatment period. Haematological assessments were done. RESULTS: The lipid formulations were safer than MN powder with LD50 values of 3162.8 and 1118.3 mg/kg. Bioavailability determination revealed a higher area under the curve (AUC) value for formulations A 1 (6.11 µg/hr/mL) and B 1 (4.91 µg/hr/mL) while formulation C 1 (1.80 µg/hr/mL) had a lower AUC than MN (4.46 µg/hr/mL). Fungi were completely cleared from the blood of animals treated with the optimized formulation by day 3 as opposed to the controls (MN and Tween® 20) which still had fungi on day 5. No significant increase (p > 0.05) in haematological parameters was observed in mice treated with A 1. CONCLUSION: Formulation A 1 successfully cleared Candida albicans from the blood within a shorter period than miconazole powder. This research has shown the potential of orally administered MN-loaded SRMS-based microparticles in combating systemic candidaemia.


Asunto(s)
Antifúngicos , Miconazol , Animales , Antifúngicos/farmacología , Disponibilidad Biológica , Candida albicans , Candidiasis , Lípidos/farmacología , Ratones , Micelas , Miconazol/farmacología , Tamaño de la Partícula , Polvos
17.
Mol Divers ; 26(6): 3447-3462, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35064444

RESUMEN

Malaria accounts for over two million deaths globally. To flatten this curve, there is a need to develop new and high potent drugs against Plasmodium falciparum. Some major challenges include the dearth of suitable animal models for anti-P. falciparum assays, resistance to first-line drugs, lack of vaccines and the complex life cycle of Plasmodium. Gladly, newer approaches to antimalarial drug discovery have emerged due to the release of large datasets by pharmaceutical companies. This review provides insights into these new approaches to drug discovery covering different machine learning tools, which enhance the development of new compounds. It provides a systematic review on the use and prospects of machine learning in predicting, classifying and clustering IC50 values of bioactive compounds against P. falciparum. The authors identified many machine learning tools yet to be applied for this purpose. However, Random Forest and Support Vector Machines have been extensively applied though on a limited dataset of compounds.


Asunto(s)
Antimaláricos , Plasmodium falciparum , Animales , Relación Estructura-Actividad Cuantitativa , Antimaláricos/farmacología , Aprendizaje Automático , Descubrimiento de Drogas
18.
Braz. J. Pharm. Sci. (Online) ; 58: e191133, 2022. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1394030

RESUMEN

Abstract The study is aimed at investigating the functional physicochemical and solid state characteristics of food-grade Tetracarpidium conophorum (T. conophorum) oil for possible application in the pharmaceutical industry for drug delivery. The oil was obtained by cold hexane extraction and its physicochemical properties including viscosity, pH, peroxide, acid, and thiobarbituric acid values, nutrient content, and fatty acid profile were determined. Admixtures of the oil with Softisan®154, a hydrogenated solid lipid from palm oil, were prepared to obtain matrices which were evaluated by differential scanning calorimetry, fourier-transform infrared spectroscopy, and x-ray diffractometry. Data from the study showed that T. conophorum oil had Newtonian flow behaviour, acidic pH, insignificant presence of hyperperoxides and malondialdehyde, contains minerals including calcium, magnesium, zinc, copper, manganese, iron, selenium, and potassium, vitamins including niacin (B3), thiamine (B1), cyanocobalamine (B12), ascorbic acid (C), and tocopherol (E), and long-chain saturated and unsaturated fatty acids including n-hexadecanoic acid, 9(Z)-octadecenoic acid, and cis-13-octadecenoic acid. The lipid matrices had low crystallinity and enthalpy values with increased amorphicity, and showed no destructive intermolecular interaction or incompatibility between T. conophorum oil and Softisan® 154. In conclusion, the results have shown that, in addition to T. conophorum oil being useful as food, it will also be an important excipient for the development of novel, safe, and effective lipid-based drug delivery systems.


Asunto(s)
Aceites/análisis , Preparaciones Farmacéuticas/administración & dosificación , Química Física/instrumentación , Euphorbiaceae/clasificación , Análisis Espectral/métodos , Sistemas de Liberación de Medicamentos/instrumentación , Alimentos/clasificación
19.
Methods Microbiol ; 50: 151-188, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-38620863

RESUMEN

The outbreak of the COVID-19 pandemic in 2019 has been one of the greatest challenges modern medicine and science has ever faced. It has affected millions of people around the world and altered human life and activities as we once knew. The high prevalence as well as an extended period of incubations which usually does not present with symptoms have played a formidable role in the transmission and infection of millions. A lot of research has been carried out on developing suitable treatment and effective preventive measures for the control of the pandemic. Preventive strategies which include social distancing, use of masks, washing of hands, and contact tracing have been effective in slowing the spread of the virus; however, the infectious nature of the SARS-COV-2 has made these strategies unable to eradicate its spread. In addition, the continuous increase in the number of cases and death, as well as the appearance of several variants of the virus, has necessitated the development of effective and safe vaccines in a bid to ensure that human activities can return to normalcy. Nanotechnology has been of great benefit in the design of vaccines as nano-sized materials have been known to aid the safe and effective delivery of antigens as well as serve as suitable adjuvants to potentiate responses to vaccines. There are only four vaccine candidates currently approved for use in humans while many other candidates are at various levels of development. This review seeks to provide updated information on the current nano-technological strategies employed in the development of COVID-19 vaccines.

20.
Adv Pharm Bull ; 11(3): 543-556, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34513630

RESUMEN

Purpose: Biosurfactants are applied in drug formulations to improve drug solubility and in some cases, treat diseases. This study is focused on generating, extracting, purifying and then characterizing biosurfactants from bacterial isolates of palm oil wastes and abattoir soil origins. Methods: Eight bacteria were isolated from the soil and sludge samples, out of which four (50%) were found to produce biosurfactants. Bacillus subtilis (37.5%) and Pseudomonas aeruginosa (50%) were isolated and identified from these samples using mineral salt medium, nutrient agar and Cetrimide agar. Mutant isolates of B. subtilis BS3 and P. aeruginosa PS2 were used to produce biosurfactants using mineral salt medium as enrichment medium and extraction was done using membrane filter. Results: The mutant strains B. subtilis BS3 and P. aeruginosa PS2 generated biosurfactants that displayed significant solubility and dissolution properties by enhancing the percentage solubility of piroxicam to 62.86 and 54.29% respectively, and achieved 51.71 and 48.71% dissolution of the drug in 0.1N HCl. Conclusion: From the results obtained, the produced biosurfactants could serve as a better alternative to conventional surfactants. Notably, the study indicated that the biosurfactant produced by mutant strain of B. subtilis produced more potent activities (surface tension reduction ability, high emulsification) than those of P. aeruginosa.

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