Microneedles: A minimally invasive delivery system for ocular treatment.

This review article delves into the extensive use of microneedles in ocular therapy, emphasizing their efficacy in delivering drug substances to the posterior region of the eye. The conventional methods of drug delivery, while widely employed, are marred by inherent drawbacks such as neovascularization, abrasion, and infiltration. To address these limitations, the review explores various approaches to microneedle fabrication, shedding light on the diverse materials employed in the process. Furthermore, the article meticulously examines the delivered drug substances using distinct microneedle approaches and their applications in ocular therapy. By critically evaluating the drawbacks associated with conventional ophthalmic drug delivery, the review seeks to pave the way for a paradigm shift. It advocates for a novel approach centered around minimally invasive microneedles, presenting them as a promising solution to overcome the limitations of current drug delivery methods. The comprehensive discussion within this article not only offers insights into the fabrication techniques and materials used for microneedles but also provides a nuanced understanding of the applications and advantages associated with this innovative approach. As the exploration of microneedle technology continues to evolve, this review serves as a valuable resource for researchers, clinicians, and pharmaceutical professionals seeking to enhance ocular therapy by embracing the potential of minimally invasive microneedles.

Exploring film forming ability and improving its bioadhesiveness by thiolation of mucilaginous polysaccharides from Cassia uniflora seeds for drug delivery application.

The objectives of the present work were to explore film forming ability of mucilaginous polysaccharides obtained from Cassia uniflora seeds and improving its bioadhesive potential by thiolation for drug delivery and other applications. Thiolation was achieved by esterification reaction with thioglycolic acid. The modification was confirmed by performing and comparing its zeta potential, DSC, and spectrophotometric characterization by FTIR and NMR with unmodified mucilaginous polysaccharide. The modified mucilaginous polysaccharides FTIR spectra showed an additional absorption band at 2565 cm-1 and new shifts appeared in the 1H (δ 3.24 and at δ 3.44 ppm) and 13C NMR spectra's (21.56 ppm) confirming the esterification of mucilaginous polysaccharides. The prepared films of thiolated and unmodified mucilaginous polysaccharides were evaluated for various parameters like thickness, pH, and weight measurement, The film formulation had a thickness of 0.16 to 0.18 mm, pH in the range of 6.79 to 7.09 and weight uniformity 0.89 to 0.94 mg. The results reveal that the films based on thiolated material improved bioadhesive properties after thiolation. The SEM photographs revealed a smooth surface of film formulations. The diclofenac-loaded film of thiolated mucilaginous polysaccharide also showed >1.5-fold an increase in in-vitro drug release and exhibited non Fickian transport mechanism. These findings could increase the possible applications of chemically modified-thiolated mucilaginous polysaccharides of Cassia uniflora seeds in drug delivery.

Pharmacokinetics of vitamin dosage forms: A complete overview.

Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier-based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency.

Surface decorated quantum dots: Synthesis, properties and role in herbal therapy.

Quantum dots are the serendipitous outcome of materials research. It is the tiny carbonaceous nanoparticles with diameters ranging from 1 to 10 nm. This review is a brief discussion of the synthesis, properties, and biomedical applicability of quantum dots, especially in herbal therapy. As quantum dots are highly polar, they can be surface decorated with several kinds of polar functionalities, such as polymeric molecules, small functional molecules, and so on. The review also consists of the basic physical and optical properties of quantum dots and their excitation-dependent properties in the application section. We focus on therapeutics, where quantum dots are used as drugs or imaging probes. Nanoprobes for several diagnostics are quite new in the biomedical research domain. Quantum dot-based nanoprobes are in high demand due to their excellent fluorescence, non-bleaching nature, biocompatibility, anchoring feasibility for several analytes, and fast point-of-care sensibility. Lastly, we also included a discussion on quantum dot-based drug delivery as phytomedicine.

Update on preoperative evaluation and optimisation.

The patients presenting for surgery today often belong to the extremes of age, have multiple co-morbidities, and undergo complex surgeries. This makes them more prone to morbidity and mortality. A detailed preoperative evaluation of the patient can contribute to reducing this mortality and morbidity. There are various risk indices and validated scoring systems and many of them need to be calculated using preoperative parameters. Their key objective is to identify patients vulnerable to complications and to return them to desirable functional activity as soon as possible. Any individual undergoing surgery should be optimised preoperatively, but special considerations should be given to patients with comorbidity, on multiple drugs, and undergoing high-risk surgery. The objective of this review is to put forth the latest trends in the preoperative evaluation and optimisation of patients undergoing noncardiac surgery and emphasise the importance of risk stratification in these patients.

Verapamil hydrochloride loaded solid lipid nanoparticles: Preparation, optimization, characterisation, and assessment of cardioprotective effect in experimental model of myocardial infarcted rats.

Verapamil, a calcium channel blocker has poor bioavailability (20-30%) owing to extensive hepatic first-pass metabolism. Hence, the major objective of this research was to improve the oral bioavailability of Verapamil by Solid Lipid Nanoparticles (V-SLNs) using high shear homogenization and ultrasonication technology. A 32 factorial design was employed to statistically optimize the formulation to get minimum particle size with maximum entrapment efficiency. The average particle size was 218 nm and the entrapment efficiency was 80.32%. The V-SLN formulation exhibited biphasic behavior with a rapid release at first, then a steady release (75-80%) up to 24 h following the Korsmeyer Peppas release model. In the Isoproterenol induced myocardial necrosis model, oral administration of V-SLNs positively modulated almost all the studied hemodynamic parameters such as left ventricular end-diastolic pressure, cardiac injury markers, and tissue architecture. The cardioprotective effect was also confirmed with histopathological studies. When compared with free drugs, in-vivo pharmacokinetic studies demonstrated a rise in t1/2, AUC0-∞, and Cmax, indicating that bioavailability has improved. These encouraging results demonstrate the promising potential of developed V-SLNs for oral delivery and thereby improve the therapeutic outcome.

In vitro and in vivo characterization of Entacapone-loaded nanostructured lipid carriers developed by quality-by-design approach.

Entacapone, a reversible catechol-o-methyl transferase inhibitor, is used to enhance the action of dopamine agonists by reducing their metabolism and the 'Wearing-off' effects associated with long-term use in the treatment of Parkinson's disease. It is used as an adjunct to levodopa/Carbidopa therapy. Due to limited dissolution and first-pass clearance, it suffers low and variable bioavailability issues. To overcome this problem, the present study aims to explore the potential of nanostructured lipid carriers (NLCs) for the delivery of Entacapone. The Quality by Design (QbD) approach was used for the systematic development of NLCs. The 23 full factorial designs were investigated using Design-Expert®11 software. The three independent variables namely content of total lipid (X1), surfactant (X2), and sonication time (X3) were optimized against two responses namely particle size and entrapment efficiency. The optimized NLCs were characterized for their size, surface morphology, entrapment efficiency, drug release, thermal and crystallographic studies. In-vivo pharmacokinetic studies in Entacapone-loaded NLCs showed an increase in t1/2, AUC0-∞, MRT compared to free drug. The reduction in elimination (Kel) depicts the prolonged action of Entacapone by loading in NLCs. The results displayed Entacapone-loaded NLCs have promising potential for oral delivery and enhanced therapeutic effect which otherwise was a major issue.

Stereolithography 3D printing technology in pharmaceuticals: a review.

Three-dimensional printing (3DP) technology is an innovative tool used in manufacturing medical devices, producing alloys, replacing biological tissues, producing customized dosage forms and so on. Stereolithography (SLA), a 3D printing technique, is very rapid and highly accurate and produces finished products of uniform quality. 3D formulations have been optimized with a perfect tool of artificial intelligence learning techniques. Complex designs/shapes can be fabricated through SLA using the photopolymerization principle. Different 3DP technologies are introduced and the most promising of these, SLA, and its commercial applications, are focused on. The high speed and effectiveness of SLA are highlighted. The working principle of SLA, the materials used and applications of the technique in a wide range of different sectors are highlighted in this review. An innovative idea of 3D printing customized pharmaceutical dosage forms is also presented. SLA compromises several advantages over other methods, such as cost effectiveness, controlled integrity of materials and greater speed. The development of SLA has allowed the development of printed pharmaceutical devices. Considering the present trends, it is expected that SLA will be used along with conventional methods of manufacturing of 3D model. This 3D printing technology may be utilized as a novel tool for delivering drugs on demand. This review will be useful for researchers working on 3D printing technologies.

Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet.

Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of -28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.

Isolation and structural characterization of mucilaginous polysaccharides obtained from the seeds of Cassia uniflora for industrial application.

In present study we explored powder of mucilaginous polysaccharides obtained from seeds of Cassia uniflora by determining its physicochemical, thermal, phytochemical, spectrophotometric and micrometric properties. The probable structure of isolated mucilaginous polysaccharide was determined using FTIR and 1H and 13C NMR spectroscopy, which demonstrated that the Cassia uniflora seed mucilage is rich in the polysaccharides residues (ß-d-glucose) in the pyranose form. The mucilage was also explored for its gelling ability. X-ray diffraction patterns indicate the mucilage was amorphous in nature. This enables its application as a gelling agent in the pharmaceutical, cosmetics and food industries. It exhibits gelling ability at 1% w/w concentration. The mucilage exhibited swelling as well as pseudo plastic behaviour and good micrometric properties. Texture profile analysis of (3% w/w) prepared gel showed comparable properties of hardness, adhesiveness, gumminess and springiness to standard tragacanth. These features allow its application in food matrices and in pharmaceutical as a gelling and thickening agent.

Burnout among Healthcare Workers during COVID-19 Pandemic in India: Results of a Questionnaire-based Survey.

BACKGROUND: Burnout, a state of physical and emotional exhaustion, in healthcare workers (HCWs) is a major concern. The prevalence of burnout, due to COVID-19 pandemic in India, is unknown. We therefore conducted this survey. MATERIALS AND METHODS: A questionnaire-based survey using Copenhagen Burnout Inventory was carried out among HCWs looking after COVID-19 patients. Questionnaire was sent to the HCWs, using WhatsApp Messenger, and voluntary participation was sought. We received responses from 2026 HCWs. Burnout was assessed in personal, work, and client-related (COVID-19 pandemic-related) domains. Burnout was defined at a cut-off score of 50 for each domain. RESULTS: The prevalence of personal burnout was 44.6% (903), work-related burn-out was only 26.9% (544), while greater than half of the respondents (1,069, 52.8%) had pandemic-related burnout. Younger respondents (21-30 years) had higher personal and work-related burnout. The prevalence of personal and work-related burnout was significantly (p < 0.01) higher among females. The doctors were 1.64 times, and the support staff were 5 times more likely to experience pandemic-related burnout. CONCLUSION: There is a significant prevalence of burnout during the COVID-19 pandemic among HCWs, in particular, doctors and support staff. Female respondents had higher prevalence. We suggest that the management should be proactive and supportive in improving working conditions and providing assurance to the HCWs. The long-term effects of the current pandemic need to be assessed later. HOW TO CITE THIS ARTICLE: Khasne RW, Dhakulkar BS, Mahajan HC, Kulkarni AP. Burnout among Healthcare Workers during COVID-19 Pandemic in India: Results of a Questionnaire-based Survey. Indian J Crit Care Med 2020;24(8):664-671.

Methotrexate-Loaded Nanostructured Lipid Carrier Gel Alleviates Imiquimod-Induced Psoriasis by Moderating Inflammation: Formulation, Optimization, Characterization, In-Vitro and In-Vivo Studies.

INTRODUCTION: Methotrexate exhibits poor cutaneous bioavailability and systemic side effects on topical administration, so there is an unmet need for a novel carrier and its optimized therapy. Methotrexate-loaded nanostructured lipid carriers (MTXNLCs) were formulated and characterized to determine in vitro drug release and evaluate the role of MTXNLC gel in the topical treatment of psoriasis. METHODS: A solvent diffusion technique was employed to prepare MTXNLCs, which was optimized using 32 full factorial designs. The mean diameter and surface morphology of MTXNLCs was evaluated. The crystallinity of lyophilized MTXNLCs was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). MTXNLCs were integrated in 1% w/w Carbopol 934 P gel base, and in vitro skin deposition studies in human cadaver skin (HCS) were carried out. RESULTS: The optimized MTXNLCs were rod-shaped, with an average particle size of 253 ± 8.65 nm, a zeta potential of -26.4±0.86 mV, and EE of 54.00±1.49%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of MTX was found in HCS from MTXNLC gel (71.52 ±1.13%) as compared to MTX plain gel (38.48±0.96%). In vivo studies demonstrated significant improvement in therapeutic response and reduction in local side effects with MTXNLCs-loaded gel in the topical treatment of psoriasis. Anti-psoriatic efficacy of MTXNLCs 100 ug/cm2 compared with plain MTX gel was evaluated using imiquimod (IMQ)-induced psoriasis in BALB/c mice. The topical application of MTXNLCs to the mouse ear resulted in a significant reduction of psoriatic area and severity index, oxidative stress, inflammatory cytokines like TNF-α, IL-1ß, and IL-6 and IMQ-induced histopathological alterations in mouse ear samples. CONCLUSION: Developed formulation of MTXNLC gel demonstrated better anti-psoriatic activity and also displayed prolonged and sustained release effect, which shows that it can be a promising alternative to existing MTX formulation for the treatment of psoriasis.

Central composite design-based optimization of lopinavir vitamin E-TPGS micelle: In vitro characterization and in vivo pharmacokinetic study.

This study was aimed at formulating Lopinavir loaded Vitamin E-TPGS micelles to enhance its oral bioavailability. Lopinavir is an HIV-1 protease inhibitor with low aqueous solubility leading to poor oral bioavailability and thus frequent dosing. Drug loaded micelles were fabricated using thin film hydration technique and optimized by two-factor five-level central composite design. For this purpose independent variables selected were TPGS to drug ratio and rotational speed of rotary evaporator, whereas dependent variables chosen were particle size and % entrapment efficiency. The effect of an independent variable on the dependent variable was studied by generating a quadratic polynomial model. Results of in vitro characterization showed that prepared lopinavir micelles exhibited particle size 91.71 nm, polydispersity index 0.129, zeta potential -24.8 mV, entrapment efficiency 99.36 ±â€¯1.06% and drug loading 20.83 ±â€¯1.23%. Results of DSC and P-XRD evaluation revealed that drugs were successfully encapsulated inside the Vitamin E-TPGS micelles. In vitro release studies displayed enhancement in drug dissolution as a result of its loading into micelles. TEM images showed that micelles were spherical. On oral administration of lopinavir micelles; the relative bioavailability was boosted by 3.17 folds compared to lopinavir suspensions. Thus, we can conclude that TPGS based micelles possess the prodigious potential to overcome the challenges of current HAART therapy.

Quercetin loaded nanoemulsion-based gel for rheumatoid arthritis: In vivo and in vitro studies.

Current research reports the development, optimization and evaluation of Quercetin (QCT) loaded nanoemulsion (NE)-based gel for the effective rheumatoid arthritis (RA) management. The formulation of QCT- NE was developed using spontaneous emulsification techniques using the Box- Behnken experimental design. The cytotoxicity study and effect on TNF-α production were evaluated respectively on HIG-82 and RAW 264.7 cells. The study showed that QCT- NE has no toxic effect on synoviocytes and a strong inhibitory effect on LPS-induced TNF-α production. QCT- NE gel has confirmed adequate rheological behavior with a good texture profile and improved drug permeation compared to free QCT gel. In addition, the gel was found to be non-irritating and showed the inhibition of paw edema in rats induced by CFA over 24 h contrary to free QCT gel. In conclusion, the formulation of QCT- NE gel is an efficient topical treatment strategy for rheumatoid arthritis.

Isolation and characterization of natural polysaccharide from Cassia Obtustifolia seed mucilage as film forming material for drug delivery.

In this work Cassia obtustifolia seed mucilage isolated and evaluated as novel excipient for drug delivery. Seed mucilage was evaluated qualitatively and quantitatively for presence of polysaccharide. A novel biodegradable film based on mucilage obtained from seeds of Cassia obtustifolia was fabricated and characterized. The microstructure, mechanical and thermal properties of the film were determined. Results of the scanning electron microscopy revealed a smooth and regular surface morphology. DSC and X-ray diffraction studies revealed an amorphous structure of Cassia obtustifolia seed mucilage films. In vitro degradation simulated body fluids and oral acute toxicity studies with high LD50 value of >2 g/kg of body weight demonstrate its safety as excipient. Diclofenac loaded film exhibited sustained drug release due to swelling and diffusion of film. These findings demonstrated that the Cassia obtustifolia seed mucilage had potential to use as film forming excipient with enhanced characteristics for drug delivery application.

Aripiprazole-Loaded Polymeric Micelles: Fabrication, Optimization and Evaluation using Response Surface Method.

AIMS AND BACKGROUND: The fundamental objective of current study was to encapsulate Aripiprazole (ARP) within Pluronic F127 micelles to improve its aqueous solubility. The recent patents on Aripiprazole (JP2013136621) and micelles (WO2016004369A1) facilitated selection of drug and polymer. MATERIALS AND METHODS: The drug-laden micelles were fabricated using thin-film hydration technique. Optimization of the micellar formulation was done by using response surface method (RSM). The Pluronic F127 concentration of 150 mg and 75 rpm rotational speed of rotary evaporator were found to be optimized conditions for formulating micelles. RESULTS: The prepared batches were further characterized for PDI (polydispersity index), zeta potential, % DLC (% Drug loading content), % EE (% Entrapment Efficiency) and % drug release study; results of these parameters were found to be 0.228, -4.04 mV and 76.50 % and 18.56 % respectively. It was observed from the In vitro release study that 97.37 ± 1.81 % drug had released from micelles after 20h which were found about thrice as compared to that of pure drug. The optimized ARP micellar formulation was characterized using DSC (Differential Scanning Colorimetry), FT-IR (Fourier Transformed Infrared Spectroscopy), P-XRD (Powdered X-ray Diffraction Study) and TEM (Transmission Electronic Microscopy) studies. ARP-loaded micelles displayed a hydrodynamic diameter of 170.3 nm and a sphere-shaped morphology as determined by dynamic light scattering as well as TEM study. CONCLUSION: It is concluded that the prepared polymeric micellar system has an excellent potential to be used as a delivery carrier for Aripiprazole with increased solubility.

Nasal inserts containing ondansetron hydrochloride based on Chitosan-gellan gum polyelectrolyte complex: In vitro-in vivo studies.

The aim of this study was the production of ondansetron hydrochloride loaded lyophilized insert for nasal delivery. The nasal insert was prepared by the lyophilisation technique using Chitosan-gellan gum polyelectrolyte complex as the polymer matrix. The ondansetron loaded inserts were evaluated with respect to water uptake, bioadhesion, drug release kinetic study, ex vivo permeation study, and in vivo study. Lyophilised nasal inserts were characterized by differential scanning calorimetry, scanning electron microscopy and X-ray diffraction study. Scanning electron microscopy confirmed the porous sponge like structure of inserts whereas release kinetic model revealed that drug release followed non-fickian case II diffusion. The nasal delivery showed improved bioavailability as compared to oral delivery. In conclusion, the ondansetron containing nasal inserts based on Chitosan-gellan gum complex with potential muco-adhesive potential is suitable for nasal delivery.

Development of grafted xyloglucan micelles for pulmonary delivery of curcumin: In vitro and in vivo studies.

A novel grafted copolymer consisting of l-lactide grafted xyloglucan was synthesized by polymerization reaction and characterized. The grafted copolymers were analyzed by Fourier-transform infrared spectrometry (FTIR) and (1)H nuclear magnetic resonance ((1)H NMR) was performed to confirm the grafting of l-poly lactic acid on xyloglucan. The grafted polymer forms micelles at the critical micelle concentration of 0.0150 wt% with the average particle size of 102 nm, as determined by particle size analyzer. The zeta potential of the curcumin loaded micelles was -18.2 mV, an acceptable drug loading efficiency of 68.9 ± 0.02% and the entrapment efficiency of 96.38 ± 0.2%. The release study for 5h showed a sustained release property. In vitro assessment demonstrates suitability of micelles as dry powder for inhalation. In vivo studies showed significant improvement in bioavailability on pulmonary administration of curcumin micelles as DPI formulation. The potential for pulmonary delivery curcumin loaded in micelles was evaluated. In conclusion, polymeric micelle based on a newly synthesized grafted xyloglucan could be suitable carrier for pulmonary delivery of curcumin.

Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study.

Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as a carrier for curcumin (CRM). The CRM-loaded NLC developed as a particle with the size of 146.8 nm, a polydispersity index of 0.18, an entrapment efficiency (EE) of 90.86%, and the zeta potential (ZP) of -21.4 mV. Besides, the increased cytotoxicity of CRM-NLC than that of CRM to astrocytoma-glioblastoma cell line (U373MG) in the cancer cell lines was observed. Results of biodistribution studies showed higher drug concentration in brain after intranasal administration of NLCs than PDS. The results of the study also suggest that CRM-NLC is a promising drug delivery system for brain cancer therapy.

Development of Suppositories Containing Flutamide-Loaded Alginate-Tamarind Microparticles for Rectal Administration: In Vitro and in Vivo Studies.

In the present work the absorption of flutamide from suppositories containing hydrophilic tamarind alginate microparticles after rectal administration in rats was investigated with the purpose of enhancing bioavailability and to avoid hepatic toxicity. Microparticles were developed by ionic gelation method and optimized using one factorial design of response surface methodology. The optimized batch of microparticles had tamarind gum-sodium alginate (1 : 3) ratio and showed entrapment efficiency 94.969% and mucoadhesion strength 94.646% with desirability of 0.961. Suppositories loaded with microparticles were developed by fusion method using poloxamer 407 and poloxamer 188 in combination as suppository base. Kinetic analysis of the release data of microparticle-loaded suppositories showed time-independent release of drug. Higher values of 'n' (>0.89) represent Super Case II-type drug release. The pharmacokinetics of flutamide from flutamide tamarind alginate microparticle-loaded suppository were compared with oral suspension. Cmax of microparticle-loaded suppository was significantly larger than that of oral suspension (1.711 and 0.859 µg/mL, respectively).