Triamcinolone acetonide-loaded PLA/PEG-PDL microparticles for effective intra-articular delivery: synthesis, optimization, in vitro and in vivo evaluation.

Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) in drug delivery is advantageous compared to polymers derived from fossil fuels. The present work aimed to produce microparticles (MPs) derived from novel sustainable polymers, loaded with triamcinolone acetonide (TA) for treatment of rheumatoid arthritis via intra-articular (IA) delivery. PDL was synthesized from green δ-decalactone monomers and co-polymerized with methoxy-polyethylene glycol (mPEG) forming PEG-PDL with different molecular weights. The Hansen's solubility parameters were applied to select the most compatible polymer with the drug. An o/w emulsion/solvent evaporation technique was used for MPs fabrication, using 3 [3] full factorial design. Selection of the optimized MPs was performed using Expert Design® software's desirability function. The optimized formulations were characterized using scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro release studies. The inhibition percents of inflammation and histopathological studies were assessed in complete Freund's adjuvant-induced rats' knee joints evaluating the effect of IA injections of selected MPs compared to the free drug suspension. Solubility studies revealed high compatibility and miscibility between TA and PEG-PDL1700, which was blended with PLA for convenient MPs formation. The in vitro characterization studies confirmed the formation of drug-copolymer co-crystals. The in vivo studies ensured the superiority of the newly designed composite MPs in inflammation suppression, compared to the free drug suspension and PLA MPs as well. The present study proved the advantage of using sustainable polymers in a novel combination for effective drug delivery and suggesting its usefulness in designing versatile platforms for therapeutic applications.

Intramatricial injections for nail psoriasis: An open-label comparative study of triamcinolone, methotrexate, and cyclosporine.

BACKGROUND: One of the most effective options available for treating psoriatic fingernails is intramatricial injection of triamcinolone acetonide. Efficacies of intramatricial methotrexate and cyclosporine have not been comparatively evaluated to date. METHODS: Ninety fingernails in 17 patients were assigned to three groups of thirty nails each, and treated with intramatricial injections of triamcinolone acetonide (10 mg/ml), methotrexate (25 mg/ml) and cyclosporine (50 mg/ml) respectively. Each nail was given two injections with a 6-week interval, and graded at 24 weeks using the Nail Psoriasis Severity Index. RESULTS: In both triamcinolone acetonide and methotrexate groups, 15 (50%) nails out of 30 showed >75% improvement. In the cyclosporine group, only ten (33%) nails showed >75% improvement. Side effects were most in the nails treated with cyclosporine. LIMITATIONS: The limited follow-up period of 24 weeks may have been insufficient for detecting delayed remissions. The number of patients was small and there was no randomization or blinding. The lack of a placebo/ no- treatment arm can be considered a limitation. CONCLUSIONS: Amongst the three drugs studied, intramatricial methotrexate injection yielded the most improvement with minimum side effects, results being comparable to intramatricial triamcinolone acetonide injection. Cyclosporine was the least effective drug, with the most side effects. Intramatricial injection therapy is a safe, economical, simple and effective therapeutic modality in the management of nail psoriasis.

Dermoscopic evaluation of therapeutic response to an intralesional corticosteroid in the treatment of alopecia areata.

BACKGROUND: Intralesional corticosteroids are the treatment of choice for adults with less than 50% of scalp area involvement with alopecia areata. The sensitivity of picking up clinical response to treatment by clinical examination is very variable and has inter individual variation. AIMS: To evaluate the efficacy of intralesional triamcinolone acetonide in the treatment of alopecia areata and to use dermoscopy to identify signs of early clinical response and adverse effects. METHODS: Seventy patches in 60 patients were injected with steroid at 4 weeks interval and followed up for 24 weeks. Treatment response was evaluated using regrowth scale (RGS). Heine DELTA 20; dermatoscope was used to assess disease activity, response to treatment and side effects. RESULTS: Twenty eight patients responded early and achieved RGS of 4 within 12 weeks and 29 patients responded late and achieved RGS of 4 within 24 weeks of initiating therapy. There were 3 patients who did not achieve RGS of 4 at 24 weeks. Late and incomplete responders showed statistically significant association with family history of alopecia areata (p < 0.0001), presence of recurrent disease (p = 0.0147) and presence of nail changes (p = 0.0007). Dermoscopically, 60 patches demonstrated regrowth of new vellus hair at 4 weeks. Tapering hair disappeared maximally at 4 weeks. At 12 weeks, complete disappearance was seen in tapering hairs, broken hairs and black dots whereas for yellow dots to disappear completely in all patches it took 16 weeks. The adverse effects were observed at an earlier stage using dermoscopy than clinically. CONCLUSION: Intralesional triamcinolone acetonide is efficacious for treatment of localized patchy alopecia areata. Dermoscopy is very useful to identify signs of early clinical response, adverse effects and markers of disease activity.

Comparison of intralesional verapamil with intralesional triamcinolone in the treatment of hypertrophic scars and keloids.

BACKGROUND: The calcium channel blocker, verapamil stimulates procollagenase synthesis in keloids and hypertrophic scars. AIM: To study the effect of verapamil in the treatment of hypertrophic scars and keloids and to evaluate the effect of verapamil on the rate of reduction of hypertrophic scars and keloids in comparison with triamcinolone. METHODS: The study was a randomized, single blind, parallel group study in which 54 patients were allocated to to receive either verapamil or triamcinolone. Drugs were administered intralesionally in both groups. Improvement of the scar was measured using modified Vancouver scale and by using a centimeter scale serially till the scar flattened. RESULTS: There was a reduction in vascularity, pliability, height and width of the scar with both the drugs after 3 weeks of treatment. These changes were present at one year of follow-up after stopping treatment. Scar pigmentation was not changed desirably by either drug. Length of the scars was also not altered significantly by either drug. The rate of reduction in vascularity, pliability, height and width of the scar with triamcinolone was faster than with verapamil. Adverse drug reactions were more with triamcinolone than with verapamil. CONCLUSION: Intralesional verapamil may be a suitable alternative to triamcinolone in the treatment of hypertrophic scars and keloids.

Incidental finding of skin deposits of corticosteroids without associated granulomatous inflammation: report of three cases.

Three cases are described in whom deposits of depot steroids were seen in skin biopsies done for diagnostic purposes. In the first case the skin lesion was clinically suspected to be due to the steroid injected more than a year ago and a diagnosis of pseudo-morphea due to steroid injection was made by the clinician. The other cases had clinical diagnoses of dermatofibroma and morphea with no clinical suspicion of previous steroid injection. The steroid deposits were present in the subcutaneous fat in all three cases. Histologically the findings were distinctive with collections of acellular, amorphous, fuzzy basophilic material surrounded by lipophages and disrupted adipocytes (in Case 2) and without any significant inflammatory infiltrate or granulomatous reaction (in Cases 1 and 3). The absence of inflammatory and granulomatous responses were the findings at variance with the cases described earlier in the literature.

Treatment of leprous neuritis by neurolysis combined with perineural corticosteroid injection.

A study on leprous neuritis, involving the ulnar nerve, was carried out on 39 patients. The evaluation of nerve function was done before and after treatment by a score chart. Patients were divided into two groups. Group A (21 patients) was subjected to neurolysis only, and group B (18 patients) were given the combined treatment of neurolysis and perineural corticosteroid injection at the same time as neurolysis and subsequently at the end of the second and third weeks. In group B, 83.3% of patients showed 10% or more increase in the posttreatment score in comparison with 57.1% in group A. Improvement was more marked in paucibacillary cases and when the duration of nerve involvement was less than 3 months. Patients with short segments of nerve involvement with minimal thickening had better recovery. This procedure was observed to be simple, easy and well accepted by the patients, with a marked beneficial effect.