Novel nano-in-micro fabrication technique of diclofenac nanoparticles loaded microneedle patches for localised and systemic drug delivery.

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.

Transdermal Delivery of Pramipexole Using Microneedle Technology for the Potential Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disease primarily impacting neurons responsible for dopamine production within the brain. Pramipexole (PRA) is a dopamine agonist that is currently available in tablet form. However, individuals with PD commonly encounter difficulties with swallowing and gastrointestinal motility, making oral formulations less preferable. Microneedle (MN) patches represent innovative transdermal drug delivery devices capable of enhancing skin permeability through the creation of microconduits on the surface of the skin. MNs effectively reduce the barrier function of skin and facilitate the permeation of drugs. The work described here focuses on the development of polymeric MN systems designed to enhance the transdermal delivery of PRA. PRA was formulated into both dissolving MNs (DMNs) and directly compressed tablets (DCTs) to be used in conjunction with hydrogel-forming MNs (HFMNs). In vivo investigations using a Sprague-Dawley rat model examined, for the first time, if it was beneficial to prolong the application of DMNs and HFMNs beyond 24 h. Half of the patches in the MN cohorts were left in place for 24 h, whereas the other half remained in place for 5 days. Throughout the entire 5 day study, PRA plasma levels were monitored for all cohorts. This study confirmed the successful delivery of PRA from DMNs (Cmax = 511.00 ± 277.24 ng/mL, Tmax = 4 h) and HFMNs (Cmax = 328.30 ± 98.04 ng/mL, Tmax = 24 h). Notably, both types of MNs achieved sustained PRA plasma levels over a 5 day period. In contrast, following oral administration, PRA remained detectable in plasma for only 48 h, achieving a Cmax of 159.32 ± 113.43 ng/mL at 2 h. The HFMN that remained in place for 5 days demonstrated the most promising performance among all investigated formulations. Although in the early stages of development, the findings reported here offer a hopeful alternative to orally administered PRA. The sustained plasma profile observed here has the potential to reduce the frequency of PRA administration, potentially enhancing patient compliance and ultimately improving their quality of life. This work provides substantial evidence advocating the development of polymeric MN-mediated drug delivery systems to include sustained plasma levels of hydrophilic pharmaceuticals.

Long-acting microneedle formulations.

The minimally-invasive and painless nature of microneedle (MN) application has enabled the technology to obviate many issues with injectable drug delivery. MNs not only administer therapeutics directly into the dermal and ocular space, but they can also control the release profile of the active compound over a desired period. To enable prolonged delivery of payloads, various MN types have been proposed and evaluated, including dissolving MNs, polymeric MNs loaded or coated with nanoparticles, fast-separable MNs hollow MNs, and hydrogel MNs. These intricate yet intelligent delivery platforms provide an attractive approach to decrease side effects and administration frequency, thus offer the potential to increase patient compliance. In this review, MN formulations that are loaded with various therapeutics for long-acting delivery to address the clinical needs of a myriad of diseases are discussed. We also highlight the design aspects, such as polymer selection and MN geometry, in addition to computational and mathematical modeling of MNs that are necessary to help streamline and develop MNs with high translational value and clinical impact. Finally, up-scale manufacturing and regulatory hurdles along with potential avenues that require further research to bring MN technology to the market are carefully considered. It is hoped that this review will provide insight to formulators and clinicians that the judicious selection of materials in tandem with refined design may offer an elegant approach to achieve sustained delivery of payloads through the simple and painless application of a MN patch.

Microneedle array patches for sustained delivery of fluphenazine: A micron scale approach for the management of schizophrenia.

Schizophrenia is a severe chronic mental illness characterised by impaired emotional and cognitive functioning. To treat this condition, antipsychotics are available in limited dosage forms, mainly oral and injectable formulations. Although injectable antipsychotics were designed to enhance adherence, they are invasive, painful and require a healthcare professional to be administered. To overcome such administration issues, extensive research has been focused on developing transdermal antipsychotic formulations. In this work, three microneedle (MN) systems were developed to deliver fluphenazine (FLU) systemically. A decanoic prodrug of FLU called fluphenazine decanoate (FLUD) was used in two of the MN formulations due to its high lipophilicity. FLU-D was loaded into dissolving MNs and nanoemulsion (NE)-loaded MNs. The parent drug FLU was loaded into poly(lactic-co-glycolic acid) (PLGA)-tipped MNs. All MN systems were characterised and evaluated in vitro and in vivo. The in vivo evaluation of the three developed MN systems showed their ability to deliver FLU into the systemic circulation, as the Cmax of FLU-D dissolving MNs was 36.11 ± 12.37 ng/ml. However, the Cmax of FLU-D NE loaded dissolving MNs was 12.92 ± 6.3 ng/ml and for FLU-PLGA tipped MNs was 21.57 ± 2.45 ng/ml. Compared to an intramuscular (IM) injection of FLU-D in sesame oil, the relative bioavailabilities were 26.96 %, 21.73 % and 42.45 % for FLU-D dissolving MNs, FLU-D NE dissolving MNs and FLU-PLGA tipped MNs, respectively. FLU plasma levels were maintained above the minimum human therapeutic limits for a week. Consequently, these various MN formulations are considered to be a viable options for the transdermal delivery of fluphenazine and its prodrug. The three MN systems developed offer patients a user-friendly, painless, and convenient long-acting delivery method for FLU. Reducing dosing frequency and using less invasive drug administration methods can enhance adherence and foster positive therapeutic outcomes. This study demonstrates the capability and adaptability of MNs technology to transport hydrophobic molecules from the skin to the systemic circulation.

Polymeric Microarray Patches for Enhanced Transdermal Delivery of the Poorly Soluble Drug Olanzapine.

Transdermal drug delivery is an alternative route of administration that offers avoidance of the associated drawbacks of orally and parenterally administered hydrophobics. However, owing to the extremely specific set of physicochemical characteristics required for passive transdermal drug permeation, the development of marketed transdermal products containing poorly soluble drugs has been severely limited. Microarray patches (MAPs) are a type of transdermal patch that differ from the traditional patch design due to the presence of tiny, micron-sized needles that permit enhanced drug permeation on their application surface. To date, MAPs have predominantly been used to deliver hydrophilic compounds. However, this work challenges this trend and focuses on the use of MAPs, in combination with commonly utilized solubility-enhancing techniques, to deliver the hydrophobic drug olanzapine (OLP) across the skin. Specifically, cyclodextrin (CD) complexation and particle size reduction were employed in tandem with hydrogel-forming and dissolving MAPs, respectively. In vivo experimentation using a female Sprague-Dawley rat model confirmed the successful delivery of OLP from hydrogel-forming MAPs (Cmax = 611.13 ± 153.34 ng/mL, Tmax = 2 h) and dissolving MAPs (Cmax = 690.56 ± 161.33 ng/mL, Tmax = 2 h) in a manner similar to that of oral therapy in terms of the rate and extent of drug absorption, as well as overall drug exposure and bioavailability. This work is the first reported use of polymeric MAPs in combination with the solubility-enhancing techniques of CD complexation and particle size reduction to successfully deliver the poorly soluble drug OLP via the transdermal route. Accordingly, this paper provides significant evidence to support an expansion of the library of molecules amenable to MAP-mediated drug delivery to include those that exhibit poor aqueous solubility.

Formulation of antiretroviral nanocrystals and development into a microneedle delivery system for potential treatment of HIV-associated neurocognitive disorder (HAND).

HIV/AIDS remains a major global public health issue. While antiretroviral therapy is effective at reducing the viral load in the blood, up to 50% of those with HIV suffer from some degree of HIV-associated neurocognitive disorder, due to the presence of the blood-brain barrier restricting drugs from crossing into the central nervous system and treating the viral reservoir there. One way to circumvent this is the nose-to-brain pathway. This pathway can also be accessed via a facial intradermal injection. Certain parameters can increase delivery via this route, including using nanoparticles with a positive zeta potential and an effective diameter of 200 nm or less. Microneedle arrays offer a minimally invasive, pain-free alternative to traditional hypodermic injections. This study shows the formulation of nanocrystals of both rilpivirine (RPV) and cabotegravir, followed by incorporation into separate microneedle delivery systems for application to either side of the face. Following an in vivo study in rats, delivery to the brain was seen for both drugs. For RPV, a Cmax was seen at 21 days of 619.17 ± 73.32 ng/g, above that of recognised plasma IC90 levels, and potentially therapeutically relevant levels were maintained for 28 days. For CAB, a Cmax was seen at 28 days of 478.31 ± 320.86 ng/g, and while below recognised 4IC90 levels, does indicate that therapeutically relevant levels could be achieved by manipulating final microaaray patch size in humans.

Revision of some mensural measurements, food preference, and haematological parameters in breeding pairs of blue rock pigeon, Columba livia sampled from Punjab Pakistan / Revisão de algumas medidas mensurais, preferência alimentar e parâmetros hematológicos em pares de criação de pombo blue rock (Columba livia), amostragem de Punjab, Paquistão

The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.

O presente estudo descreve o perfil hematológico, a preferência alimentar e a comparação de caracteres morfométricos de casais reprodutores de pombo-rocha (Columba livia). Para tanto, 25 pares (25 amostras por sexo) foram amostrados por meio de redes de névoa do distrito de Okara e Bahawalnagar, Punjab, Paquistão. As aves foram então anestesiadas com uma combinação de cetamina HCL (10 mg/kg) e diazepam (0,2 mg/kg) e submetidas a medidas morfométricas; 5 µL de sangue também foram retirados da veia jugular de cada ave anestesiada para análise hematológica. Poucos pares também foram dissecados para remover o trato gastrointestinal (GITs) para preferências alimentares. Os resultados revelaram que não há diferenças significativas nos parâmetros hematológicos e na preferência alimentar dos casais reprodutores de Columba livia. A análise intestinal revelou ainda que a maior parte do conteúdo intestinal consistia em ervilha e milho na maioria dos pares. Em relação às medidas mensurais, foram registradas diferenças significativas no peso corporal, comprimento da pena primária mais longa e circunferência torácica, enquanto os demais parâmetros estudados permanecem não significativos entre os sexos. Assim, conclui-se que além de três parâmetros morfométricos (peso corporal, comprimento da pena primária mais longa e circunferência torácica), ambos os sexos são semelhantes em termos de morfometria, hematologia e preferência alimentar.

Revision of some mensural measurements, food preference, and haematological parameters in breeding pairs of blue rock pigeon, Columba livia sampled from punjab Pakistan

Abstract The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.

Resumo O presente estudo descreve o perfil hematológico, a preferência alimentar e a comparação de caracteres morfométricos de casais reprodutores de pombo-rocha (Columba livia). Para tanto, 25 pares (25 amostras por sexo) foram amostrados por meio de redes de névoa do distrito de Okara e Bahawalnagar, Punjab, Paquistão. As aves foram então anestesiadas com uma combinação de cetamina HCL (10 mg/kg) e diazepam (0,2 mg/kg) e submetidas a medidas morfométricas; 5 µL de sangue também foram retirados da veia jugular de cada ave anestesiada para análise hematológica. Poucos pares também foram dissecados para remover o trato gastrointestinal (GITs) para preferências alimentares. Os resultados revelaram que não há diferenças significativas nos parâmetros hematológicos e na preferência alimentar dos casais reprodutores de Columba livia. A análise intestinal revelou ainda que a maior parte do conteúdo intestinal consistia em ervilha e milho na maioria dos pares. Em relação às medidas mensurais, foram registradas diferenças significativas no peso corporal, comprimento da pena primária mais longa e circunferência torácica, enquanto os demais parâmetros estudados permanecem não significativos entre os sexos. Assim, conclui-se que além de três parâmetros morfométricos (peso corporal, comprimento da pena primária mais longa e circunferência torácica), ambos os sexos são semelhantes em termos de morfometria, hematologia e preferência alimentar.

Revision of some mensural measurements, food preference, and haematological parameters in breeding pairs of blue rock pigeon, Columba livia sampled from punjab Pakistan / Revisão de algumas medidas mensurais, preferência alimentar e parâmetros hematológicos em pares de criação de pombo blue rock (Columba livia), amostragem de punjab, Paquistão

Abstract The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.

Resumo O presente estudo descreve o perfil hematológico, a preferência alimentar e a comparação de caracteres morfométricos de casais reprodutores de pombo-rocha (Columba livia). Para tanto, 25 pares (25 amostras por sexo) foram amostrados por meio de redes de névoa do distrito de Okara e Bahawalnagar, Punjab, Paquistão. As aves foram então anestesiadas com uma combinação de cetamina HCL (10 mg/kg) e diazepam (0,2 mg/kg) e submetidas a medidas morfométricas; 5 µL de sangue também foram retirados da veia jugular de cada ave anestesiada para análise hematológica. Poucos pares também foram dissecados para remover o trato gastrointestinal (GITs) para preferências alimentares. Os resultados revelaram que não há diferenças significativas nos parâmetros hematológicos e na preferência alimentar dos casais reprodutores de Columba livia. A análise intestinal revelou ainda que a maior parte do conteúdo intestinal consistia em ervilha e milho na maioria dos pares. Em relação às medidas mensurais, foram registradas diferenças significativas no peso corporal, comprimento da pena primária mais longa e circunferência torácica, enquanto os demais parâmetros estudados permanecem não significativos entre os sexos. Assim, conclui-se que além de três parâmetros morfométricos (peso corporal, comprimento da pena primária mais longa e circunferência torácica), ambos os sexos são semelhantes em termos de morfometria, hematologia e preferência alimentar.

The clinical and translational prospects of microneedle devices, with a focus on insulin therapy for diabetes mellitus as a case study.

Microneedles have the clinical advantage of being able to deliver complex drugs across the skin in a convenient and comfortable manner yet haven't successfully transitioned to medical practice. Diabetes mellitus is a complicated disease, which is commonly treated with multiple daily insulin injections, contributing to poor treatment adherence. Firstly, this review determines the clinical prospect of microneedles, alongside considerations that ought to be addressed before microneedle technology can be translated from bench to bedside. Thereafter, we use diabetes as a case study to consider how microneedle-based-technology may be successfully harnessed. Here, publications referring to insulin microneedles were evaluated to understand whether insertion efficiency, angle of insertion, successful dose delivery, dose adjustability, material biocompatibility and therapeutic stability are being addressed in early stage research. Moreover, over 3,000 patents from 1970 to 2019 were reviewed with the search term '"microneedle" AND "insulin"' to understand the current status of the field. In conclusion, the reporting of early stage microneedle research demonstrated a lack of consistency relating to the translational factors addressed. Additionally, a more rational design, based on a patient-centred approach is required before microneedle-based delivery systems can be used to revolutionise the lives of people living with diabetes following regulatory approval.

Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery.

The oral route is the most common and practical means of drug administration, particularly from a patient's perspective. However, the pharmacokinetic profile of oral drugs depends on the rate of drug absorption through the intestinal wall before entering the systemic circulation. However, the enteric epithelium represents one of the major limiting steps for drug absorption, due to the presence of efflux transporters on the intestinal membrane, mucous layer, enzymatic degradation, and the existence of tight junctions along the intestinal linings. These challenges are more noticeable for hydrophilic drugs, high molecular weight drugs, and drugs that are substrates of the efflux transporters. Another challenge faced by oral drug delivery is the presence of first-pass hepatic metabolism that can result in reduced drug bioavailability. Over the years, a wide range of compounds have been investigated for their permeation-enhancing effect in order to circumvent these challenges. There is also a growing interest in developing nanocarrier-based formulation strategies to enhance the drug absorption. Therefore, this review aims to provide an overview of the challenges faced by oral drug delivery and selected strategies to enhance the oral drug absorption, including the application of absorption enhancers and nanocarrier-based formulations based on in vitro, in vivo, and in situ studies.

Hydrogel-forming microarray patches with cyclodextrin drug reservoirs for long-acting delivery of poorly soluble cabotegravir sodium for HIV Pre-Exposure Prophylaxis.

Hydrogel-forming microarray patches (HF-MAPs) offer minimally invasive, pain-free and prolonged drug delivery. These devices are designed to be self-administered and self-disabling, avoiding contaminated sharps waste generation. Cabotegravir sodium (CAB-Na) is a poorly soluble anti- human immunodeficiency virus (HIV) drug for the treatment and pre-exposure prophylaxis of HIV infection that lends itself to depot formation following intradermal delivery but presents significant challenges when delivered via HF-MAPs, whose nature is aqueous. Herein, we have investigated, for the first time, the use of hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to enhance the solubility of CAB-Na, and its effect on intradermal delivery via HF-MAPs. Accordingly, tablet reservoirs containing CAB-Na and HP-ß-CD were formulated. These novel reservoirs were combined with two different HF-MAP formulations (MAP1 (Gantrez S97® + poly (ethylene glycol) 10,000 + Na2CO3) and MAP2 (poly (vinyl pyrrolidone) 58 kDa + poly (vinyl alcohol) 85-120 kDa + citric acid)) to form fully integrated MAP devices which were tested in both ex vivo and in vivo settings. Ex vivo skin deposition results for MAP1 and MAP2 showed that 141 ± 40 µg and 342 ± 34 µg of CAB-Na was deposited into 0.5 cm2 of excised neonatal porcine skin after 24 h, respectively. Based on these findings, the in vivo pharmacokinetics of MAP2 were investigated over 28 days using a Sprague-Dawley rat model. After 24 h patch application, MAP2 demonstrated an extended drug release profile and an observed Cmax of 53.4 ± 10.16 µg/mL, superior to that of an FDA-approved CAB-nanosuspension administered via intramuscular application (Cmax of 43.6 ± 5.3 µg/mL). Consequently, this tablet integrated MAP device is considered to be a viable option for the intradermal delivery of hydrophobic anti-HIV drugs.

Revision of some mensural measurements, food preference, and haematological parameters in breeding pairs of blue rock pigeon, Columba livia sampled from punjab Pakistan.

The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.

Intradermal delivery of imiquimod using polymeric microneedles for basal cell carcinoma.

Despite being one of the most efficacious drugs used in the treatment of basal cell carcinoma (BCC), imiquimod has limited cutaneous permeation. The current work presents the development of polyvinylpyrrolidone-co-vinyl acetate (PVPVA) microneedles loaded with imiquimod for improving intradermal delivery of imiquimod for the treatment of nodular BCC. In vitro permeation studies, using full thickness ex vivo porcine skin were used to evaluate the effectiveness of these imiquimod loaded polymeric microneedles in comparison to the topical application of commercial Aldara™ cream. HPLC analysis demonstrated similar intradermal permeation of imiquimod from Aldara™ cream and imiquimod-loaded microneedles despite the microneedle having a six-fold lower drug loading than the clinical dose of Aldara™ used for BCC management. In addition, ToF-SIMS analysis of skin cross sections demonstrated intradermal localisation of imiquimod following microneedle-based delivery while the Aldara™ treated skin showed the drug localised predominantly within the stratum corneum. ToF-SIMS analysis also demonstrated intradermal co-localisation of the PVPVA polymer, used in fabricating the microneedle, with imiquimod within the microneedle channels in a label-free manner. This study demonstrates that a polymeric microneedle system may be a viable approach to improving the intradermal delivery of imiquimod for the treatment of nodular BCC with lower drug loading.

Development and characterisation of ibuprofen-loaded nanoemulsion with enhanced oral bioavailability.

Lipophilic compounds constitute a majority of therapeutics in the pipeline of drug discovery. Despite possessing enhanced efficacy and permeability, some of these drugs suffer poor solubility necessitating the need of a suitable drug delivery system. Nanoemulsion is a drug delivery system that provides enhanced solubility for poorly soluble drugs in an attempt to improve the oral bioavailability. The purpose of this study is to develop a nanoemulsion system using ibuprofen as a model drug in order to investigate the potential of this colloidal system to enhance the absorption of poorly water-soluble drugs. Ibuprofen loaded-nanoemulsion with different drug concentrations (1.5, 3 and 6% w/w) were formulated from olive oil, sucrose ester L-1695 and glycerol using D-phase emulsification technique. A pseudoternary phase diagram was utilised to identify the optimal excipient composition to formulate the nanoemulsion system. In vitro diffusion chamber studies using rodent intestinal linings highlighted improved absorption profile when ibuprofen was delivered as nanoemulsion in comparison to microemulsions and drug-in-oil systems. This was further corroborated by in vivo studies using rat model that highlighted a two-fold increase in ibuprofen absorption when the drug was administered as a nanoemulsion relative to drug-in-oil system. On the other hand, when ibuprofen was administered as microemulsions, only a 1.5-fold increase in absorption was observed relative to drug-in-oil system. Thus, this study highlights the potential of using nanoemulsion as a drug delivery system to enhance the oral bioavailability of hydrophobic drugs.

Intradermal and transdermal drug delivery using microneedles - Fabrication, performance evaluation and application to lymphatic delivery.

The progress in microneedle research is evidenced by the transition from simple 'poke and patch' solid microneedles fabricated from silicon and stainless steel to the development of bioresponsive systems such as hydrogel-forming and dissolving microneedles. In this review, we provide an outline on various microneedle fabrication techniques which are currently employed. As a range of factors, including materials, geometry and design of the microneedles, affect the performance, it is important to understand the relationships between them and the resulting delivery of therapeutics. Accordingly, there is a need for appropriate methodologies and techniques for characterization and evaluation of microneedle performance, which will also be discussed. As the research expands, it has been observed that therapeutics delivered via microneedles has gained expedited access to the lymphatics, which makes them a favorable delivery method for targeting the lymphatic system. Such opportunity is valuable in the area of vaccination and treatment of lymphatic disorders, which is the final focus of the review.

Expanding the applications of microneedles in dermatology.

Since the first patent for microneedles was filed in the 1970s, research on utilising microneedles as a drug delivery system has progressed significantly. In addition to the extensive research on microneedles for improving transdermal drug delivery, there is a growing interest in using these devices to manage dermatological conditions. This review aims to provide the background on microneedles, the clinical benefits, and challenges of the device along with the potential dermatological conditions that may benefit from the application of such a drug delivery system. The first part of the review provides an outline on benefits and challenges of translating microneedle-based drug delivery systems into clinical practice. The second part of the review covers the application of microneedles in treating dermatological conditions. The efficacy of microneedles along with the limitations of such a strategy to treat diseased skin shall be addressed.

Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment.

Basal cell carcinoma (BCC) is the most common skin cancer in humans. Topical treatment with imiquimod provides a non-invasive, self-administered treatment with relatively low treatment cost. Despite displaying excellent efficacy, imiquimod is only licensed by the FDA for superficial BCC. The current work employed HPLC and ToF-SIMS analysis to provide a novel assessment of imiquimod permeation from Aldara™ cream in skin depth and lateral distribution. Using Aldara™ cream and in vitro Franz cell studies with subsequent HPLC analysis, it is apparent that most of the topically applied imiquimod cream is left on the skin surface with more than 80% of the drug being recovered from skin wash. In addition, ToF-SIMS chemical imaging of recovered tape stripped skin samples illustrated significant detection of imiquimod signal over the entire skin area for the upper tape strips, whereas the deeper strips show large portions of the skin area without detected imiquimod. Given the limited permeation depth and non-uniform permeation observed at tape strips 6-18 when applied as a topical imiquimod cream, a permeation enhancement strategy utilising a skin pre-treatment with a microneedle device was investigated as a method to improve intradermal delivery. The recovered amount of imiquimod in tape strips and remaining skin determined by HPLC was approximately three times higher when Aldara™ was applied on microneedle pre-treated skin relative to intact skin. The ToF-SIMS ion images of the tape strips and cross-sections illustrated the existence of imiquimod in the microchannels which then laterally diffuses to peripheral epidermal strata. The current work demonstrates the first known attempt to enhance intradermal delivery of imiquimod using a microneedle device as well as underscoring the complementary role of ToF-SIMS analysis in chemically mapping imiquimod permeation into the skin with high sensitivity.

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.